This is “Where Things Grow Back!”

We are currently involved in a Research Study on a special process of purifying bone marrow or BMA using a system designed by Emcyte Corporation. We are working with Bio Sciences Research Center at Harvard and offering a great opportunity for special pricing on treatment. Call our office for details.

Prolotherapy & Platelet Rich Plasma with

 Wellington Chen, M.D., Raette Hall PA-C,  John Lieurance, D.C. & Alex Smithers, AP, DOM & the Gecko Team.

Years of experience and training in the field of regenerative injections are why you might choose these physicians as your doctors for these treatments. Platelet Rich Plasma Therapy or PRP is Prolotherapy using your own blood. Your blood is placed into a machine that looks like a record player. The platelet rich plasma is spun down and this solution is then injected into area’s that are damaged or arthritic.

Click on one of the button’s below to explore videos and information on how Gecko’s Regenerative therapies work on some specific conditions.

Gecko Joint & Spine is Sarasota’s Regenerative Clinic!

Wellington Chen, M.D. attended Northestern University, University of Pennsylvania, University of Florida, and UF Dept. of Anesthesiology.

Emergency Medical Work includes: Citrus Memorial Hospital, Inverness, FL, Encino Hospital, Ca (Dir of Emergency Medicine, 1978 – 1983) , Glendale Memorial Hospital, Venice HospitalFlorida , Doctors Hospital, Sarasota Englewood Hospital, Florida, Citrus Memorial Hospital,Crystal River, Florida.

He studied through the University of Wisconsin as well as with the orthomolecular Institute on both Prolotherapy and Platelet Rich Plasma Therapy. He has been performing Prolotherapy for 10 years and was the first to offer PRP as well as adipose and bone marrow stem cell treatments in Sarasota, Florida.

Raette Hall PA-C, R.V. T. is a board certified Florida licensed Physician Assistant since Rae Hall large2007. Raette received her education in Cleveland Ohio and was trained at the Cleveland Clinic. She has worked in physical medicine using ultrasound guided injection. She is highly trained in joint and soft tissue injections, prolotherapy, PRP and the use of stem cell Injections for non surgical orthopedics. She is member of American Association on Physician Assistants. In addition, she is a Registered Vascular Technologist since 2003 and is a member of The American

Alex Smithers, DOM, AP 

AlexReceived his graduate degree from the East West College of Natural Medicine where he excelled in his understanding and practical application of both Eastern and Western Medicine.In addition to his Oriental Medical knowledge, he has an equal proficiency in Western Medical diagnosis, which resulted under the tutelage of the great Dr. Banerjee M.D. FACE (Listed in Best Doctors of America). Dr. Smithers is a board certified Doctor of Oriental Medicine and Acupuncture Physician. A native of Sarasota, Dr. Smithers’ family has a long and well-known history in the community. Dr. Smithers work with Prolozone, Prolotherapy and other regenerative therapies as well as High Definition Ultrasound. His knowledge of both Eastern and Western medicine gives him a special gift in this field of medicine.

John A. Lieurance, D.C.

has been using Musculoskeletal Ultrasound since 1998 and has extensive training through Gulf Coast Ultrasound Institute, American Association of Orthopedic Medicine and the American Osteopathic Association of Prolotherapy Regenerative Medicine. Dr. Lieurance often assists in the diagnosis of the injuries at Gecko Joint and Spine as well as the guidance of the needle when the treatment is injected which aids in the precision of the treatment. Dr. Lieurance and Dr. Chen have been working as a team for 8 years. He attended Parker College of Chiropractic and has a Bachelor in Anatomy from the University of the State of New York. He received his Naturopathic degree in 2001 from St. Lukes School of Medicine.   Dr. Lieurance has a gift for difficult cases where other practitioners have failed. His Chiropractic, Naturopathic and use of Ultrasound gives the center an edge in the treatment of difficult cases. He has been working along side Prolotherapy procedures for 17 years  after his Chiropractic career was saved through prolotherapy in 1997.

“We are commited to offering the finest and most advanced regenerative injection therapies to my patients in a warm, caring and of course most comfortable/ pain free way possible.”

About PRP therapy.

This is a video explaining PRP.

This video shows how ligament damage can often be the cause of chronic neck pain.

Watch this video on PRP regenerating Cartilage.


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Posted in Back Pain, Knee pain, neck pain, Platelet Rich Plasma, Prolotherapy, TMJ | Tagged , , , , , , , , , , , , , , , , , , , , , , , , , , , | 1 Comment

Poor outcomes of revision arthroscopic type II superior labral anterior posterior repairs. (PRP and stem cell)

Abstract

BACKGROUND:

Outcomes of arthroscopic type II superior labral anterior posterior (SLAP) repairs have been reported with success. However, published data regarding outcomes of revision arthroscopic type II SLAP repairs are lacking.

HYPOTHESIS:

Outcomes of revision arthroscopic type II SLAP repairs are inferior to those of primary repairs.

STUDY DESIGN:

Case series; Level of evidence, 4.

METHODS:

A retrospective chart review was performed to identify patients who had undergone revision arthroscopic type II SLAP repairs at our institution. Patients who underwent concomitant rotator cuff repairs or labral repairs for instability were excluded. Twelve patients were contacted, and the following outcome data were prospectively gathered: American Shoulder and Elbow Surgeons (ASES) score, patient satisfaction level, return to work, return to sports, and physical examination. Demographics and intraoperative report data were also collected from the charts.

RESULTS:

The mean age at the time of revision arthroscopic type II SLAP repairs was 32.6 years (range, 19-67 years) with a mean follow-up of 50.5 months (range, 8-81 months). There were 5 workers’ compensation patients and 6 overhead athletes. Pain was the chief complaint at the time of initial and revision SLAP repairs. The mean ASES score was 72.5, patient satisfaction level was 6.4 (scale of 0-10), mean return to work was at 57.8% of the previous level, and mean return to sports was at 42.2% of the previous level. In overhead athletes, mean return to sports was at 41.3% of the previous level, and none of the 4 baseball players returned to preinjury level. The mean values for all outcome data and range of motion values were lower in workers’ compensation patients. There were no reported complications, but 2 patients required additional arthroscopic surgeries.

CONCLUSION:

Arthroscopic revision type II SLAP repairs yield worse results than primary repairs as reported in the literature, with workers’ compensation patients and overhead athletes doing especially worse. A larger prospective study of this relatively rare procedure is needed to better determine which patients may benefit from this procedure.

Comments:

The above recent study published in the American Journal of Sports Medicine analyzed the post-surgical outcomes of athletes with SLAP lesions (superior labrum anterior to posterior tears).1 179 military athletes were used in the study, all of which underwent surgery to fix an existing SLAP lesion. Out of all the operations, 36.8% of these surgeries were considered a “failure” and 28% had to be redone. That means that 66 individuals had a failed surgery and 51 had to go back into the operating room once again. At two to five year follow-ups, a significant amount of these athletes still had decreased range of motion in the affected shoulder. Researchers concluded that an age greater than 36 years old was the factor that was associated with an increased chance of surgery failure. Other studies have shown similar statistics with many participants unable to ever return to their previous pre-surgery activity level. An alternative to surgery for SLAP lesions is Platelet Rich Plasma and or Stem Cell Injections!

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Amazing abilities of adipose derived stem cell therapy to regenerate a broken finger joint.

http://Geckojointandspine.com  This is a video showing the amazing abilities of adipose derived stem cell therapy to regenerate a broken finger joint. There was a loss of motion and chronic pain with his finger after a fracture. Stem cells along with PRP where injected into the finger joint under ultrasound guidance. Results where great! (941) 330-8553.

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Bone marrow mesenchymal stem cells and platelet-rich plasma for ligament and cartilage regeneration.

How does PRP enhance stem cell treatments?

Platelet Rich Plasma (PRP) has the ability to both increase stem cells and guide them in healing. In initial findings, PRP assisted stem cells in “figuring out” what they needed to be – whether a cartilage cell, or a bone cell, or a collagen cell for ligaments and tendons. Here is what the science says: “Platelet-rich plasma has recently emerged as a potential biologic tool to treat acute and chronic tendon disorders. The regenerative potential of PRP is based on the release of growth factors that occurs with platelet rupture. Its autologous nature [the recipient and donor are one and the same person] gives it a significant advantage in tissue engineering applications.”5 So the platelets are already attuned to provide a healing environment or “scaffold” to build on. In the research cited, results confirmed that PRP enhances MSC stem cell proliferation and suggested that PRP causes chondrogenic differentiation of MSC in vitro – the platelets told the stem cells what to do.

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Lin BN, Whu SW, Chen CH, Hsu FY, Chen JC, Liu HW, Chen CH, Liou HM. Bone marrow mesenchymal stem cells, platelet-rich plasma and nanohydroxyapatite-type I collagen beads were integral parts of biomimetic bone substitutes for bone regeneration. J Tissue Eng Regen Med. 2012 Jun 28. doi: 10.1002/term.1472. [Epub ahead of print]

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Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial.

Platelet-rich plasma vs hyaluronic acid to treat knee degenerative pathology: study design and preliminary results of a randomized controlled trial.

Filardo G, Kon E, Di Martino A, Di Matteo B, Merli ML, Cenacchi A, Fornasari PM, Marcacci M.

Source

Nano-Biotechnology Laboratory, Rizzoli Orthopaedic Institute, Via di Barbiano n. 1/10, Bologna 40136, Italy.

Abstract

BACKGROUND:

Platelet rich plasma (PRP), a blood-derived product rich in growth factors, is a promising treatment for cartilage defects but there is still a lack of clinical evidence. The aim of this study is to show, through a randomized double blind prospective trial, the efficacy of this procedure, by comparing PRP to Hyaluronic Acid (HA) injections for the treatment of knee chondropathy or osteoarthritis (OA).

METHODS:

109 patients (55 treated with HA and 54 with PRP) were treated and evaluated at 12 months of follow-up. The patients were enrolled according to the following inclusion criteria: age > 18 years, history of chronic (at least 4 months) pain or swelling of the knee and imaging findings of degenerative changes of the joint (Kellgren-Lawrence Score up to 3). A cycle of 3 weekly injections was administered blindly. All patients were prospectively evaluated before and at 2, 6, and 12 months after the treatment by: IKDC, EQ-VAS, TEGNER, and KOOS scores. Range of motion and knee circumference changes were measured over time. Adverse events and patient satisfaction were also recorded.

RESULTS:

Only minor adverse events were detected in some patients, such as mild pain and effusion after the injections, in particular in the PRP group, where a significantly higher post-injective pain reaction was observed (p=0.039). At the follow-up evaluations, both groups presented a clinical improvement but the comparison between the two groups showed a not statistically significant difference in all scores evaluated. A trend favorable for the PRP group was only found in patients with low grade articular degeneration (Kellgren-Lawrence score up to 2).

CONCLUSIONS:

Results suggest that PRP injections offer a significant clinical improvement up to one year of follow-up. However, conversely to what was shown by the current literature, for middle-aged patients with moderate signs of OA, PRP results were not better than those obtained with HA injections, and thus it should not be considered as first line treatment. More promising results are shown for its use in low grade degeneration, but they still have to be confirmed.

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Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid.

Treatment of knee joint osteoarthritis with autologous platelet-rich plasma in comparison with hyaluronic acid.

Spaková T, Rosocha J, Lacko M, Harvanová D, Gharaibeh A.

Source

Associated Tissue Bank of Faculty of Medicine UPJS, Kosice, Slovakia.

Abstract

OBJECTIVE:

This study aimed to find a simple, cost-effective, and time-efficient method for the preparation of platelet-rich plasma (PRP), so the acquired benefits will be readily available for multiple procedures in smaller outpatient clinics and to explore the safety and efficacy of the application of PRP in the treatment of degenerative lesions of articular cartilage of the knee.

DESIGN:

The study was designed as a prospective, cohort study with a control group. A total of 120 patients with Grade 1, 2, or 3 osteoarthritis according to the Kellgren and Lawrence grading scale were enrolled in the study. One group of patients was treated using three intra-articular applications of PRP, and the second group of patients was given three injections of hyaluronic acid. Outcome measures included the Western Ontario and McMaster Universities Osteoarthritis Index and the 11-point pain intensity Numeric Rating Scale.

RESULTS:

On average, a 4.5-fold increase in platelet concentration was obtained in the PRP group. No severe adverse events were observed. Statistically significantly better results in the Western Ontario and McMaster Universities Osteoarthritis Index and Numeric Rating Scale scores were recorded in a group of patients who received PRP injections after a 3- and 6-mo follow-up.

CONCLUSIONS:

Our preliminary findings support the application of autologous PRP as an effective and safe method in the treatment of the initial stages of knee osteoarthritis. Further studies are needed to confirm these results and to investigate the persistence of the beneficial effects observed.

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Temporomandibular Dysfunction and Migraine in Sarasota Florida

TMD often coexists with daily or near-daily headache syndromes but is overlooked by many physicians in the history and physical examination.

Headaches typically begin as episodic disorders but certain causative factors influence the progression from episodic to daily or near-daily head-ache disorders. Over the last five years, multiple epidemiological studies have identified common risk factors for transformation of episodic to chronic migraine. The most common risk factors include: obesity, socioeconomic status, medication overuse, and previous head trauma.1 Under-recognized and easily treatable patients are those who have developed myofascial pain syndromes of the head and neck with subsequent dramatic worsening of previously benign headache syndromes. These patients will not typically respond to traditional headache preventatives until the myofascial pain syndrome is addressed. This article discusses such a case and presents an approach to these patients.

Case Report

A 40 year-old white female with 8 years of menstrual-associated migraine is referred to the author for “worsening migraines” of three months duration which occurred after a “hard fall.” During the fall, she landed on her right arm and shoulder without head injury. She has seen her family physician, dentist, a rheumatologist, and at least one other neurologist for this condition. Her main complaint is one of headaches with a Headache Impact Test-6 (HIT-6) score of 69 (previously 40). The pain was primarily on the right side and was associated with nausea, photophobia, phonophobia, osmophobia, and visual aura on most days. Gabapentin, topiramate, and extended release divalproex prophylaxis were not helpful and she was requiring near-daily short acting narcotics. The initial exam revealed myofascial trigger points in the right masseter and medial pterygoid and an otherwise normal neurological examination. She was given a two-week detailed headache diary and pain location chart. At her two week follow-up visit, the diary and pain charts revealed right jaw and facial pain in addition to her right hemicranial migraines. The jaw and facial pain was dull and aggravated by chewing. The patient’s husband confirmed nocturnal bruxism. The headache met ICDH-II criteria (see Table 1) for medication overuse headache.2

Discussion

Temporomandibular dysfunction (TMD) encompasses problems involving the temporomandibular joint or associated structures, as well as the masticatory musculature. Primary headache disorders have been shown to occur significantly more often in TMD patients and vice-versa.3,4,5 One small trial has demonstrated a significant decrease in headache frequency compared to placebo with TMD treatment.6 To the author’s knowledge, no larger studies have been published.

Increasingly over the last decade, scientific data have strengthened the author’s belief that noxious stimuli in the head and neck regions can lead to secondary sensitization of the trigeminal system. From a clinical perspective, this sensitization may, in turn, lower the migraine ‘threshold’ in susceptible patients. Pain models relating central sensitization and myofascial trigger points have already been developed for tension-type headaches.7

The author’s history evaluation in these patients includes HIT-6 score, detailed headache questionnaire, and pain location charts and diaries. The HIT-6 was developed to evaluate a patient’s headache-associated disability over the previous four weeks. A score between 60 and 78 indicates severe impairment. The author prefers the HIT-6 over the more popular Migraine Disability Assessment (MIDAS) questionnaire that evaluates headache disability over the previous 12 weeks.

For examination of a patient similar to the case presented, the author includes a thorough evaluation of the head and neck musculoskeletal system in addition to a routine neurological examination. This includes palpation of the extra-oral masticatory musculature of the face and jaw, the temporal tendon, and medial pterygoid intra-orally. While examination of the medial pterygoid can be performed intraorally or extraorally, the author prefers an intraoral technique. Placing a gloved index finger (right hand to examine the left medial pterygoid) posterior and buccal to the last upper molar, use the thumb to oppose the index finger with the muscle and ramus of the mandible between. Try this on yourself to refine the technique.

Examination of jaw function, such as opening measurements and temporomandibular joint articular palpation, are also included in the examination.

Cessation of bruxism with an oral appliance is an appropriate goal but may not be enough to achieve the desired clinical effect. The author prefers trigger point injections in combination with tricyclic antidepressants—such as amitriptyline or nortriptyline—or the muscle relaxer, tizanidine, along with an appropriate oral appliance. Others have used spray and stretch techniques in place of trigger point injections.8 With any headache syndrome, if medication overuse is present it must be addressed. Strategies for medication-overuse treatment are beyond the scope of this article. Most patients do not respond to pharmacological migraine prevention only and so the myofascial pain syndrome and the headache syndrome must be simultaneously addressed.

Outcome

The patient was counseled about medication overuse and withdrawn from daily narcotics. The patient did not tolerate multiple nighttime oral appliances fabricated by her dentist. She was also concerned about weight gain associated with the tricyclic antidepressants. She was given trigger point injections in the masseter and medial pterygoid and oral bedtime tizanidine. This resulted in complete resolution of her jaw pain and a return to her previous episodic migraine pattern. Interestingly, no specific methods were used to treat her medication-overuse problem other than education about the condition. Periodically, she requires “booster” trigger-point injections, but her need for this is becoming less frequent.

Conclusion

This article describes a patient who had a stable, episodic migraine pattern that was aggravated by temporomandibular dysfunction. Diagnosis and treatment of the TMD led to a return of her previous migraine pattern after traditional migraine preventatives failed. Myofascial pain of the head and neck, including TMD, must be adequately addressed to return refractive headache syndromes to a more stable and manageable episodic level.Screen Shot 2013-07-13 at 8.31.20 AM

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Platelet Rich Plasma (PRP) Matrix Grafts in Sarasota Florida

PRP application techniques in musculoskeletal medicine utilize the concentrated healing components of a patient’s own blood—reintroduced into a specific site—to regenerate tissue and speed the healing process.

Platelet Rich Plasma (PRP) grafting techniques are now being utilized in musculoskeletal medicine with increasing frequency and effectiveness. Soft tissue injuries treated with PRP include tendonopathy, tendonosis, acute and chronic muscle strain, muscle fibrosis, ligamentous sprains, and joint capsular laxity. PRP has also been utilized to treat intra-articular injuries. Examples include arthritis, arthrofibrosis, articular cartilage defects, meniscal injury, and chronic synovitis or joint inflammation.

Platelet Rich Plasma was first used in cardiac surgery by Ferrari et al. in 1987 as an autologous transfusion component after an open heart operation to avoid homologous blood product transfusion.1 It is now being utilized by musculoskeletal (MSK) providers following the effective use in multiple specialties. PRP has also been successfully used in various specialties such as maxillofacial, cosmetic, spine, orthopedic, podiatric and for general wound healing.2,3

MSK practitioners began using PRP for tendonosis and tendonitis in the early 1990s.4 PRP techniques have most commonly been applied by MSK practitioners previously trained in the use of—and on the knowledge backbone of—prolotherapy. Although there is a paucity of well designed, randomized trials for its use in MSK medicine, animal studies, case reports, and anecdotal evidence suggests that this technique will continue to develop as a way to regenerate tissue that has lost its inherent homeostasis and thereby relieve associated pain and dysfunction.

Standardizing the Nomenclature for PRP

The authors define a PRP Matrix Graft as follows:

A tissue graft incorporating autologous growth factors and/ or autologous undifferentiated cells in a cellular matrix whose design depends on the receptor site and tissue of regeneration.

In reading the literature, different verbiage will arise, such as platelet leukocyte gel, platelet rich plasma gel, platelet concentrate, blood plasma therapy, etc. When examining the literature, one must evaluate whether concentrations of platelets, nucleated cells, growth factors, fibrin, and platelet activation is measured. These factors— along with skillful percutaneous injection and surgical techniques—all contribute to the effectiveness of therapy.5 Everts, on reviewing 28 human studies, found that seven showed either no benefit or negative effects of PRP.3 However, when these studies were reviewed, many had very small sample sizes (as few as three patients) and several had platelet portions that had been activated prior to use via differing means. Hopefully, in the near future, the nomenclature will benefit from some form of standardization. It is the authors’ experience, however, that the wording of ‘graft’ is required in the nomenclature for third party reimbursement reasons, as well as to accurately describe how this modality is actually utilized at present in the clinic and surgical settings.

For our purposes, we will consider PRP gel as PRP that is activated with either autologous thrombin and calcium, bovine thrombin and calcium, or thrombin alone. Autologous PRP gel stipulates the use of autologous thrombin. The author considers a PRP Matrix Graft to include gel or no gel. This must be stipulated at the time of treatment. Again, the tissue of treatment will demand what matrix, if any, is added or utilized.

Constituents and Properties of an Effective Regenerative Graft

Normal tissue homeostasis is maintained in a prescribed physiologic manner. These stages will be reviewed from a hypothetical time of injury through the healing phase to understand how to maximize PRP graft matrix preparation. Platelets contain two unique types of granules—the alpha-granules and dense granules.

Alpha-granules contain a variety of hemostatic proteins (coagulation proteins), as well as growth factors, cytokines, chemokines (pro-inflammatory activation-inducible cytokines) and other proteins such as adhesion proteins.6 Of primary interest to the clinician are the three adhesion molecules and seven growth factors present in the alpha granule.7

Dense granules contain factors that promote platelet aggregation (ADP, calcium, serotonin). Cell activation of platelets causes the discharge of granule contents. In other words, platelets require activation in order to begin the cascade of events that lead to collagen restoration and growth. This activation must occur at the tissue level (where the platelets aggregate and adhere to collagen at the site of grafting).5

A synopsis of the various growth factors in PRP, together with their source and function, is presented in Table 1.

A PRP Matrix Graft is made in a clinical or operative setting by using one of the several available table-top machines on the market. Several authors offer reviews of available graft preparation centrifuges and their ability to concentrate growth factors.2,3,8 Each machine has a separate, disposable unit that concentrates platelets in a small amount of plasma. A thin layer of platelets is found immediately above the leukocytes in the buffy coat of centrifuged blood. When a concentrated platelet portion is made, the buffy coat containing elevated levels of leukocytes—along with concentrated platelets—are suspended in a small amount of plasma for subsequent grafting. The clinician hopes that the platelets are not activated and remain suspended until grafting and contact with thrombin or collagen occurs.

Necessary Stages of Healing

Normal platelet activation leads to three necessary stages of healing: Inflammation, Proliferation, and Remodeling.9 The cellular components involved in the three phases of healing are depicted in Figure 1. If any of these stages are incomplete—or if they proceed unabated—tissue homeostasis is lost and pain and loss of function may result. Most reviews on this topic focus on only the growth factors contained within the alpha granule of the platelet which is released upon platelet activation. It is important to understand, however, that if the platelets aren’t suspended with biologic levels of other constituents of plasma—such as leukocytes, cytokines, and fibrin (the matrix)—the graft is either not effective or less effective.3 If fibrin levels are too high, or platelet activation occurs prior to collagen binding, the graft is also inhibited. Other functions of platelet activation and the subsequent cascade of events that occur include cytokine signaling, chemokine release, and mitogenesis.9

 

Table 1. Synopsis of growth factors present in PRP
Growth Factor Source Function
Transforming Growth Factor-beta,TGF-ß Platelets, extracellular matrix of bone, cartilage matrix, activated TH1 cells and natural killer cells, macrophages/ monocytes and neutrophils Stimulates undifferentiated mesenchymal cell proliferation; regulates endothelial, fibroblastic and osteoblastic mitogenesis; regulates collagen synthesis and collagenase secretion; regulates mitogenic effects of other growth factors; stimulates endothelial chemotaxis and angiogenesis; inhibits macrophage and lymphocyte proliferation
Basic Fibroblast Growth Factor,bFGF Platelets, macrophages, mesenchymal cells, chondrocytes, osteoblasts Promotes growth and differentiation of chondrocytes and osteoblasts; mitogenetic for mesenchymal cells, chondrocytes and osteoblasts
Platelet Derived Growth Factor,PDGFa-b Platelets, osteoblasts, endothelial cells, macrophages, monocytes, smooth muscle cells Mitogenetic for mesenchymal cells and osteoblasts; stimulates chemotaxis and mitogenesis in fibroblast/glial/smooth muscle cells; regulates collagenase secretion and collagen synthesis; stimulates macrophage and neutrophil chemotaxis
Epidermal Growth Factor,EGF Platelets, macrophages, monocytes Stimulates endothelial chemotaxis/angiogenesis; regulates collagenase secretion; stimulates epithelial/mesenchymal mitogenesis
Vascular endothelial growth factor,VEGF Platelets, endothelial cells Increases angiogenesis and vessel permeability, stimulates mitogenesis for endothelial cells
Connective tissue growth factor,CTGF Platelets through endocytosis from extracellular environment in bone marrow. Promotes angiogenesis, cartilage regeneration, fibrosis and platelet adhesion
Table 1. Synopsis of growth factors present in PRP From Peter A.M. Everts et al. Platelet-Rich Plasma and Platelet Gel: A Review3

Figure 2. Relationship of differing platelet concentrations and human mesenchymal stem cell (hMSC) migration and proliferation. From: Haynesworth, Stephen et al. Mitogenic Stimulation of Human Mesenchymal Stem Cells by Platelet Releasate.11 Used with permission.Figure 3. Cell Proliferation Triangle.

Inflammatory Phase

During the inflammatory phase, the functions of activated platelets include:

  • Anti-microbial
  • Adhesion
  • Aggregation
  • Clot retraction
  • Pro-coagulation
  • Cytokine signaling
  • Chemokine release
  • Growth factor release

There is now evidence to suggest that at certain concentrations, or dose response curves, platelet rich plasma grafts may be anti-inflammatory or pro-inflammatory in certain tissues.10 A dose response relationship exists to a currently unknown level of PRP concentration and ensuing migration and proliferation of progenitor stem cells at the tissue injury site11 (see Figure 2)

There is emerging evidence to suggest that PRP grafts in the four- to six-fold range (106 platelets) have more anti-inflammatory mediators and effects and are clinically relevant and useful for most situations. PRP grafts in the eight- to thirteen-fold range may be pro-inflammatory in nature.10 Further elucidation of this effect is required, however, as some studies showed beneficial effects of higher concentrations of PRP.12

Hesham El-Sharkawy et al. evaluated this effect in periodontal tissue. The conclusions were that PRP is a rich source of growth factors and promoted significant changes in monocyte-mediated proinflammatory cytokine/chemokine release. LXA4 was increased in PRP, suggesting that PRP may suppress cytokine release, limit inflammation, and thereby promote tissue regeneration.10

Weibrich et al. observed an advantageous effect with platelet concentrations of approximately 106/µL. Further, they state that higher concentrations might have a paradoxically inhibitory effect.13

Following the initial inflammatory phase, which typically lasts for two to three days, fibroblasts enter the site and begin the proliferative phase.9 Low pH and low oxygen levels stimulate fibroblast proliferation in the injury site.14 Fibroblasts become the most abundant cell by the seventh day. The fibroblasts are then responsible for deposition of collagen and ground substance. This phase lasts from two to four weeks. As these are primarily the deficient cells with chronic injury (lack of normal collagen in extracellular matrix), this stage is mandatory for MSK repair.

The Proliferative Phase

During the proliferative phase—peaking anywhere from day 5 to 15 and which can last for weeks—fibroblasts differentiate into myofibroblasts and actin contracts to make the wound smaller. Low pH and hypoxemia also stimulates neovascularization. Neovessels begin to form at approximately day 5 to 7 and this process proceeds until the neovessels disappear near completion of the remodeling phase.

The Remodeling Phase

During the remodeling phase, collagen matures and strengthens. Tissue repair starts when the production and break down of collagen equalizes. This phase can last over one year. During this period, type III collagen is replaced by type I collagen, reorganization occurs, and the blood neovessels disappear.9

Cell Proliferation Triangle

It has become apparent, then, that PRP grafts function via a triad of interactions, known as the cell proliferation triangle16,17 (see Figure 3). Each element of this triangle must be present for effective tissue repair and pain relief.

When preparing a graft for clinical use, the constituents of each of these three must be considered—i.e. is there an inherent matrix to place the graft in, or will the graft be washed away with motion, synovial fluid, or repeated graft compression or distraction? Does the patient have an adequate response for inflammation and is there an adequate quantity of platelets to concentrate for progenitor cell mitogenesis and proliferation?

Biotensegrity—A Construct for Regeneration of Tissue

Biotensegrity refers to a dynamic construct of compressive and tensional forces acting on, and through, multiple levels of organization to maintain or repair tissue homeostasis. Biotensegrity, then, is a repeated pattern of structural and functional architecture of all living tissue.19,20

Endothelial cells line the lumen of all blood vessels as a single squamous epithelial cell layer. They are derived from angioblasts and hemangioblasts. Weibel-Palade bodies are specialized secretory granules found in endothelial cells. These vesicles store preformed hormones, cytokines, and growth factors; as well as enzymes, receptors, and adhesion molecules; which can be released and/or expressed on the cell surface without de novo protein syntheses by regulated exocytosis in response to stimulation of cell activation.6

Thus, the authors believe there is sufficient evidence to suggest that the vascular endothelial system links all of the biotensegrity levels together as the various factors are at work up and down the scale.

Contraindications to the Use of PRP Matrix Grafts3,21,

Absolute Contraindications include:

Relative Contraindications include:

Risks Involved with the Use of PRP Matrix Grafts

While there have been no reports of worsened pain or function following tissue maturation that the authors could find, few randomized, placebo controlled trials exist regarding the utilization of these grafts. In the primary author’s experience of performing approximately 20 to 30 cases of percutaneous PRP Matrix Grafts per week for the last two years, no patients reported worsened pain or function. It is felt by the authors—and often expressed in the available literature— that this procedure technique is safe and effective.

Pain at the treatment site is common for a short period following injection. One of the primary author’s patients reported worsened pain for six months at a treated lateral epicondyle. This subsequently resolved and has been absent for over one year. This stresses the fact that remodeling of the tissue is necessary to see the effects of therapy. No tendon rupture or partial rupture was noted and the authors can find no reports of tendon or ligament rupture following PRP. In fact, Olena Virchenko and Per Aspenberg noted, in a rat achilles tendon transection model, that one postoperative injection resulted in increased strength after four weeks. This effect was obliterated with the use of botox at the site.18

Other risks that may occur at time of injection include injury from pain-induced syncope. Indeed, the main complaint received from patients is the injection pain of the PRP. There is also the risk of limb injury following the graft procedure since local or regional anesthesia is used at the time of procedure. The primary author had a patient who stepped from a ladder about four hours following an achilles and peroneal tendon injection, with subsequent inversion and fracture of the ankle—most likely due to proprioceptive and sensory loss from anesthesia.

As with any percutaneous needle technique, there is a slight risk of puncturing a hollow organ or infection, but this risk is not expected to be above or below that of other needle techniques employed in clinical medicine. The accepted risk of introduction of infection with percutaneous techniques has been reported as 1:50,000 injections. Since PRP is an autologous preparation, the risk of introducing foreign material and the risk of transmissible infection or allergic reaction is effectively eliminated—although the entire procedure must be carried out in sterile conditions. PRP—with its initial inflammatory phase—is also bacteriocidal, particularly against Stapholococcus aureus and Escherichia coli as shown by Bielecki et al.22 The temporary formation of platelet and fibrin plugs at the wound site has also been noted to prevent the entry of microorganisms.3,22 However, PRP gel seems to induce the in vitro growth of Ps. aeruginosa, suggesting that it may cause an exacerbation of infections with this organism. There was no activity against Klebsiella pneumoniae or Enterococcus faecalis.

Other considerations come into play if the procedure is not performed with completely autologous preparations. PRP gel techniques that rely upon the use of bovine thrombin, which may contain contaminants like bovine Factor Va as a platelet activation source, may result in antibodies to Factors V and VI, with potentially life threatening coagulopathies resulting.5 Other concerns with bovine thrombin include prion disease, although none are reported in the literature. The authors have neither seen nor heard of any infections occurring with the percutaneous use of PRP or biocellular therapeutic grafts.

Regarding the question of carcinogenesis, growth factors act on cell surface receptors only, do not enter the cell, and do not cause DNA mutation. There is no plausible mechanism by which growth factors would result in neoplastic development, and there have been no reports of this in the literature.3,21Furthermore, Scott and Pawson showed that growth factors (PGF) activate normal, rather than abnormal, gene expression.23

Typical Treatment Regimen with PRP

Consent

Risks

Technique for Myotendinous or Teno-Osseous Sites

Technique For Intra-Osseous Sites

“Eight weeks after the treatment, the platelet-rich plasma patients noted 60% improvement in their visual analog pain scores versus 16% improvement in control patients… At 6 months, the patients treated with platelet-rich plasma noted 81% improvement in their visual analog pain scores…”

It should be noted that Kevy and Jacobson have evaluated the mixture of common local anesthetics with PRP and find no significant platelet activation or diminution of graft growth factor functions.7,24

Tendonosis and the Use of PRP

Anitua showed—from in vitro studies of collagen and tendon—that autologous preparations rich in growth factors promote proliferation and induce VEGF and HGF production by human tendon cells in culture.25 Mishra performed an in vitro study which determined the effect of a platelet concentrate medium on the proliferation of human skin fibroblasts—the cells responsible for deposition of collagen. Buffered PRP was shown to augment human fibroblast proliferation when compared to control.26

Schnabel evaluated gene expression patterns, DNA, and collagen content of equine flexor digitorum tendons cultured in a media consisting of PRP and other blood products. PRP at 100% concentration stimulated the greatest number of collagen type I, collagen type III, and cartilage oligomeric protein (COMP) molecule genes without increasing expression of the pro-inflammatory matrix metalloproteinases. ELISA detected higher levels of PDGF and TGF-B in the PRP group.27

Hesham El-Sharkawy et al.10 measured platelet derived growth factor (PDGF)-AB, PDGF-BB, transforming growth factor-b1, insulin-like growth factor-I, fibroblast growth factor-basic (FGF-b), epidermal growth factor (EGF), vascular endothelial growth factor, interleukin-12 (p40/70) and, regulated on activation, normal T-cell expressed and secreted (RANTES) levels by enzyme-linked immunosorbent assay. Cytokine, chemokine, and LXA4 levels, as well as monocyte chemotactic migration, were analyzed. PRP led to significantly increased levels of growth factors and significantly suppressed inflammation by promoting secretion of LXA4.

These growth factors stimulated the proliferation of fibroblasts and periodontal ligament cells, as well as extracellular matrix formation, and promoted collagen and total protein synthesis while stimulating the synthesis of hyaluronate from gingival fibroblasts. IGF-I levels in PRP in this study were not significantly different from the cyclolignan picropodophyllin (PPP), suggesting that other cell types could be responsible for the release of this growth factor.10

Tissue culture studies performed by du Toit et al. for use in dermal regeneration confirmed the potent mitogenic stimulation of human fibroblasts, keratinocytes, chondroc

In Vivo Human Studies: Reviews and Case Examples

Tendon and Ligament Use of PRP

Mishra evaluated 20 patients that failed non-operative treatment for chronic epicondylar pain. These 20 patients were randomized to a single PRP injection or injection with bupivicaine. Mishra comments that the IRB would not allow a blood draw from the control patients to blind the study. All PRP patients had lower pain and greater ROM than control (bupivicaine). Eight weeks after the treatment, the platelet-rich plasma patients noted 60% improvement in their visual analog pain scores versus 16% improvement in control patients. Sixty percent (three of five) of the control subjects withdrew or sought other treatments after the 8-week period, preventing further direct analysis. Therefore, only the patients treated with platelet-rich plasma were available for continued evaluation. At six months, the patients treated with platelet-rich plasma noted 81% improvement in their visual analog pain scores (P=.0001). At final follow-up (mean, 25.6 months; range, 12-38 months), the platelet-rich plasma patients reported 93% reduction in pain compared with before treatment (P29

Barrett et al. demonstrated, in a series of nine plantar fascia patients, that PRP—with ultrasound guidance—could be safely injected into the medial and central bands of the most affected plantar fascia with promising results. Seven out of nine patients had complete resolution of their plantar fascial pain at one year and all the patients in the study had improvement that was noted on diagnostic ultrasound. One of the patients was considered a failure because of a subsequent steroid injection even though all pain had resolved.30

Scarpone reported on a prospective study carried out in 14 patients with shoulder pain. The patients all had rotator cuff tears with no significant AC joint thickness with impingement and no other significant symptomatic pathology such as labral tears, glenohumeral arthrosis, or gross instability. All of the patients failed non-operative treatments such as NSAIDs, physical therapy, and corticosteroid injections and all were considering surgical options. Of the 14 patients, 12 had statistically significant improvements in their pain scale and their strength and endurance at eight weeks. Of the 12 patients, six had radiographic evidence of healing of their tendinopathy on MRI at eight weeks. Of the four patients who were considering surgery because of persistent pain, only two went on to have rotator cuff surgery. No significant complications were noted.31

Ventura et al. evaluated PRP in ACL repair. A total of 20 patients with anterior cruciate ligament (ACL) injuries were treated by quadrupled hamstring tendon graft (QHTG)—with or without PRP gel growth factor (GF) application. CT highlighted a significant difference (P32

Sanchez reported on a case-control study of twelve athletes with complete achilles rupture. All twelve had open achilles repair; six had PRGF. The treatment group had no wound complications and experienced earlier functional restoration: ROM (7 vs. 11 wks), jogging (11 vs. 18 wks), and training (14 vs. 21 wks). The authors of this study measured IGF-1, TGF-B1, PDGF-AB, EDF, VEGF, and HGF and noted that the number of platelets held direct correlation to the level of growth factors.33

Case Example: Chronic Tendonopathy

A 63-year-old male ironman distance triathlete presented with a history of left achilles pain longer than three months. The patient had no relief with physical therapy or ultrasound (U/S) therapy for a six week duration. The patient was diagnosed by MRI with stress fracture of the fibula with no discrete cortical line or fracture in addition to an achilles tendonopathy. Diagnostic U/S in our office showed an 8cm segment of tendon collagen change consistent with a tendonopathy with associated peritenon fibrosis (see Figure 4).

The patient undergoes three separate series of PRP at four-week intervals to the achilles tendon and fibula along with the peroneal tendon sheath at the myotendinous junction. Subsequent ultrasounds show improved fibrosis and less scarring along with collagen pattern reorganization consistent with improved vascularity and tendon structure (see Figure 5).

The patient has greater than 90% pain reduction after the three PRP matrix grafts and returns to ironman distance racing after the three months of restricted training. Supportive compression sleeves are utilized for three months to allow for load distribution until strength in the peroneal muscles and achilles is 90% of the unaffected right side.

Muscle Strain and the Use of PRP

Sanchez reported a 20 patient prospective muscle injury pilot study with six-month follow-up. Ultrasound guided injection of PRP within the injured muscle enhanced healing (echo-graphic images) and functional capacities 50% faster than the control group.34

Case Example: Quadriceps VMO Muscle Strain

A 56-year-old male presented with right thigh pain occurring for approximately one year. The pain is worse on the bike and, in fact, is more prevalent when seated and pushing large gears or uphill climbing. The patient has no significant pain with running. The patient is an ironman distance triathlete and remembers no injury of significance one year ago at onset. Ultrasound shows a vastus medialis injury/strain pattern with associated fiber tearing and fibrosis. This is near the VMO myotendinous junction at the right knee (see Figure 6). No evidence of knee pathology is noted on physical exam or on ultrasound. Palpable tenderness exists at the strain site on the medial thigh. Pain is also reproduced on eccentric loading of the VMO muscle group. No improvement had been obtained previously with three weeks of NSAID use, physical therapy, or myofascial therapy work.

The patient undergoes a single injection of PRP (4cc) along with 1cc of injectable collagen for matrix stabilization at two discrete sites in the VMO muscle with ultrasound guidance (see Figure 7).

The patient’s pain after one month is more than 80% resolved and the patient has no pain on the bike or with activity as previously noted. Resumption of training occurred one week following injection with swimming, running, and protected cycling.

 

Articular Cartilage and the Intra-Articular Use of PRP

Everts, Devilee, et al. reported that autologous platelet gel and fibrin sealant enhance the efficacy of total knee arthroplasty by improved range of motion, decreased length of stay, and a reduced incidence of arthrofibrosis. Everts’ team also investigated whether the use of autologous derived platelet gel and fibrin sealant would reduce postoperative blood loss, decrease the impaired range of motion, and reduce the incidence of arthrofibrosis. Study group patients (n=85) were treated with the application of autologous platelet gel and fibrin sealant at the end of surgery. Eighty patients were operated without the use of platelet gel and fibrin sealant and served as the control group. During a five-month postoperative period, patients were followed to observe the incidence of arthrofibrosis. In patients in the treatment group, the hemoglobin concentration in blood decreased significantly less when compared to the control group. They also showed a superior postoperative range of motion when compared to those of the control group (P35

Case Example: Severe Hip Osteoarthritis With a History of Congenital Hip Dysplasia

A 56-year-old female presented with increasing left hip pain greater than one year duration. The patient has a history of bilateral hip dislocations at birth (birth country Poland — no x-rays available) with evidence of shallow acetabular deformity noted on x-ray (see Figure 8).

The patient is active in dance and is of normal weight and BMI. Some relief is obtained with NSAID therapy but pain is now affecting sleep and is interfering with activities of daily living and her dance regimen. The patient undergoes one PRP injection to the left hip using an anterior approach. 8cc PRP is placed with ultrasound guidance as noted (see Figure 9).

After 3 months, the patient reports 75% pain improvement and some improvement in ROM is also reported. The night pain has resolved and the patient’s pain is controlled with acetaminophen. She is able to resume dance and activities for fitness and health.

Bone and Periosteal Use of PRP

Gandhi et al. observed normalized cellular proliferation and chondrogenesis with an improved mechanical strength when PRP was injected percutaneously in a diabetic experimental femur fracture model.36

Sanchez et al. utilized PRP after reattachment of a large (2 cm) loose chondral body in its crater in the medial femoral condyle. Autologous plasma (PRP) was injected into the area between the crater and the fixed fragment. They state that complete articular cartilage healing was considerably accelerated, and the functional outcome was excellent, allowing a rapid resumption of symptom-free athletic activity.37

PRP has been used successfully in maxillofacial surgery in several studies including a randomized trial of 88 patients with mandibular defects treated with cancellous cellular marrow grafts with, or without, PRP. Grafts with PRP showed twice the radiographic maturity at six months follow up.2

Another case report describes a fifty-year old woman with nonunion of humerus who had undergone two unsuccessful operations. Union was obtained by the use of autologous platelet-rich gel (PRG). At the 8th week, over 75% of the circumference of the bone at the defect site had resolved and, during later visits, remodeling of the union was observed on X-ray films and DEXA examinations. Maximum healing was reached at the 18th week. Twelve months after PRG injection, the intramedullary nail that had previously been placed was removed.38

Case Example: Bilateral Pars Interarticularis Stress Fractures (Spondylolysis)

A 14-year-old softball player presented with a history of developing back pain over a period of six weeks, made worse following a minor motor vehicle crash four weeks prior to visit. The patient had initial pain and localized tenderness on the right low back L4-5 area with a positive stork test. X-ray and MRI confirm spondylolysis (see Figure 10).

The patient undergoes extensive physical therapy for approximately 8 months with subsequent relief. The patient then returns to sport specific activity but redevelops pain. After appropriate discussion of the benefits and risks, a PRP matrix graft is placed on the right L5-S1 facet joint and the L5 pars with ultrasound guidance. On return to activity, the patient notes the absence of pain on the right pars or low back area. The patient is allowed to slowly return to activity. Two months following the initial PRP graft, the patient develops pain in the opposite, left lumbar area after repeated throwing drills. A repeat MRI shows a left sided spondylosis. No listhesis is appreciated. Evidence of healing is noted on the right pars stress fracture to a small degree (see Figure 11).

A PRP matrix graft—with a total 8cc PRP at a six-fold concentration and mixed with 2 cc 50:50 lidocaine 1% with marcaine 0.5%—is then placed an additional X3 on the right and X3 on the left, with approximately 5cc placed at the levels of the L5 pars as well as the accompanying facet joints. The patient is started on physical therapy at two weeks into the graft injection series with progression at 6 weeks to pilates therapy and then sport specific activity with heavy focus on the mechanics of core stabilization and kinetic chain reintegration. A repeat MRI is obtained two months following PRP (see Figure 12).

Figure 12 shows interval slight healing of the fracture sites. The patient has not developed any reoccurrence of pain and is back to softball activities with no bracing. No tenderness remains at the prior fracture sites on physical exam.

In Vivo Studies: Skin Healing, Range of Motion, and Pain with the Use of PRP

A prospective, single-blind pilot study comprising 80 full-thickness skin punch wounds (4mm diameter) was conducted on the thighs of eight healthy volunteers. With each subject serving as his or her own control (five punch sites per leg), PRP was applied topically on one thigh, while an antibiotic ointment and/or a semi-occlusive dressing was applied on the other thigh. On day 17, the percentage of closure was 81.1% for the PRP-treated sites and 57.2% for the control sites. Also, the PRP wound closure velocities were significantly faster than those of the controls (P=.001). When the platelet count in the gel was more than six times the baseline intravascular platelet count in some subjects, epithelialization and granulation formation appeared three days earlier in the PRP-treated group.39

Everts et al. noted improved wound healing when platelet leukocyte gel was applied during wound closure after total knee arthroplasty.5

In a study examining PRP gel for diabetic foot ulcers, Driver et al. noted that 13 of 19 patients in the study group (68.4%) had complete healing, compared with only 9 of 21 (42.1%) of the control group (saline gel). This study was a prospective, randomized, controlled trial with both groups receiving a blood draw for blinding purposes. The treating providers and patients were blinded to the gel applied. It should be noted that no treatment serious adverse events were reported and bovine thrombin used for PRP gel did not cause any Factor V inhibition.

In another study from Everts et al., platelet leukocyte gel (PLG) was injected in the subacromial space during wound closure in patients who underwent an open subacromial decompression.41 In the PLG-treated patients, a decrease in the VAS pain score was observed (P

A significant reduction in pain was also observed after PRP use by Fanning et al. after applications in gynecologic surgery42; Gardner and co-workers following total knee replacement surgery43; and Crovetti and associates in patients with chronic wounds.44

Conclusion

PRP matrix grafts along with other biologic grafting techniques are becoming more prevalent in the treatment paradigms of musculoskeletal medicine. These PRP matrix grafts provide effective, safe, relatively low-cost treatment options to patients who have the time and wherewithal to allow collagen synthesis and maturation at the graft site. PRP matrix grafts appear to restore tissue homeostasis and biotensegrity of collagen. Other pain inhibiting effects are also present in PRP matrix grafts which allow earlier resumption of pain free activity. It is the authors’ experiences that these grafts, along with other regenerative grafting options, are at times the only viable treatment option for a select group of patients with degenerative myofascial tissue injuries. The authors recommend appropriate first line therapies such as relative rest, appropriate bracing and kinesiotaping, evaluation of kinetic chain mechanics, and physical therapy—with or without eccentric loading protocols—prior to the utilization of these PRP matrix grafting protocols.

Reduction in pain after PRP applications has been observed by several authors. However, an explanation of this phenomena has not always been given. The authors believe that serotonin released from activated platelets might be responsible for decreased pain, as described by Everts41 and Fanning.42 Except for the growth factors in the Alpha-granules, large amounts of serotonin45 are contained within the dense platelet granules. Since platelet counts of the PRP are generally almost six-fold higher when compared to whole blood levels, it stands to reason that serotonin levels are therefore also significantly increased at the wound site. This phenomena has been explained in detail by Sprott et al.46 who reported on pain reduction following acupuncture and measured a decrease in serotonin concentration in platelets from these patients and an increase in serotonin levels in plasma—suggesting normalization of plasma serotonin levels due to the mobilization of platelet serotonin.

Other grafting tools such as the use of autologous bone marrow aspirate stem cells (BMAC) with PRP matrices have not been explored in this article but may be found in further detail by the authors. These stem cell/growth factor grafts are being utilized for severe degenerative states with associated tissue hypoxemia. Hence, PRP and other regenerative biocellur therapeutic matrices deserve further study to determine their effects in animal and human models.

  • Platelet dysfunction syndrome
  • Critical thrombocytopenia
  • Hypofibrinogenemia
  • Hemodynamic instability
  • Septicemia
  • Sensitivity to bovine thrombin (if using bovine thrombin with calcium to make platelet gel)
    • Consistent use (anti-inflammatory use) of NSAID’s within 48 hours of procedure
    • Corticosteroid injection at treatment site or systemic use of corticosteroids within 2 weeks of graft procedure
    • Recent fever or illness
    • Rash at graft donor site or at receptor site
    • Cancer — especially hematopoetic or of bone
    • Active history or history of Pseudomonas, Enterococcus or Klebsiella infection, as PRP has been shown in one study to potentially stimulate these pathogens.22
    • HGB
    • Platelet count less than 105/µL
    • Average series of injections is two to three at four- to six-week intervals
    • Different sites or areas of treatment may expand or contract with further treatment
    • You must functionally retrain the kinetic chain once the tissue has undergone some degree of healing
    • 1:50,000 chance of introducing infection with injection procedure
    • Allergy to local anesthetic(s)
    • Syncope with pain/blood at the time of injection
    • Injury occurence with numbness or pain following procedure. i.e. falling, ankle sprain with inversion, etc.
    • Though extremely rare, pain or function may worsen
    • Puncture of tissue outside of intended graft site. i.e. vascular, neural, lung, or other tissue placements
    • • Alcohol or Betadyne prep (we prefer Betadyne gel when using an ultrasound probe for ‘live’ injection guidance)
    • +/- Ethyl Chloride spray
    • Inject PRP with approximately 1cc PRP per cm3 of tissue/interface
    • Important to touch bone and ‘pepper’ the area of teno-osseous junction to stimulate the greatest number of fibroblast colonies
    • For myotendinous sites use ultrasound to ensure layered treatment throughout the tendon
    • Sterile band-aid applied post injection
    • Kinesiotape to protect motion if needed
    • Alcohol or Betadyne prep (we prefer Betadyne gel when using an ultrasound probe for ‘live’ injection guidance)
    • +/- Ethyl Chloride spray
    • Local anesthetic either mixed with the PRP graft or to sites of tenderness to ‘road test’ the area prior to using the graft. This ensures that the PRP matrix graft is placed in the proper areas.
    • Aspirate degenerative joint fluid prior to PRP matrix graft placement
    • Gel the PRP or utilize other stabilizing matrix for intra-articular sites. Ligaments, tendons, and inherent matrix sites do not require gel in the authors’ experience
    • 8-10cc PRP matrix graft is the typical amount used for a knee or shoulder joint in our clinic
    • “Treat regionally, not locally”(D. Crane, MD; e.g. treat all of the capsule that is tender along with tendinous and ligamentous sites of tenderness in addition to the intra-articular capsule)

The probable link though all levels of biotensegrity is the vascular endothelial system with its regenerative and neuroendocrine functions as subsequently described.

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Advances in Regenerative Medicine: Pure Platelet-rich Plasma and Stem Cell Prolotherapy For Musculoskeletal Pain

Prolotherapy is a method of regenerative injection treatment designed to stimulate healing.1 Prolotherapy is used for the treatment of chronic musculoskeletal pain, inclucing ligament, tendon and joint injuries, as well as osteoarthritis. The termprolotherapy is short for proliferation therapy, as it stimulates the proliferation and repair of injured tissue.

Traditional dextrose prolotherapy originated in the 1930s and continues to be used successfully. In the 2000s, in-office platelet-rich plasma (PRP) prolotherapy was introduced. This method uses a patient’s own blood, centrifuged to concentrate growth factor–rich platelets as the proliferation formula. In the past few years, physicians have began using adult stem cells, harvested from an individual’s fat tissue or bone marrow during an in-office procedure, then combined with the individual’s PRP as the proliferation formula for injection into injured musculoskeletal tissue.

This newest form of prolotherapy, known as stem cell prolotherapy, is used in difficult cases or where accelerated musculoskeletal healing is desired. Popular media reports have been emerging that cite the use of stem cell prolotherapy in professional athletes such as Bartolo Colon, starting pitcher for the New York Yankees, who had the procedure successfully done for a rotator cuff injury earlier this year.Our article will review the history, science, methodology, and evidence for these types of prolotherapy, and offer a treatment algorithm.

Prolotherapy: The Original Regenerative Medicine
Prolotherapy was “discovered” in the 1930s by Dr. Earl Gedney, an osteopathic surgeon, before the term regenerative medicine existed. However, prolotherapy is a true regenerative medicine, working by locally raising growth factor levels to promote tissue repair and regeneration.3-5

Multiple studies confirm the effectiveness of prolotherapy in the resolution of musculoskeletal pain, including low back pain,6,7 neck pain, and whiplash injuries8; chronic sprains and/or strains; tennis and golfer’s elbow9; plantar fasciitis10; knee,11 ankle, shoulder pain, coccyxdynia12; chronic tendonitis/tendonosis,13 including Achilles tendonitis/tendonosis14; and other joint pain or musculoskeletal pain related to osteoarthritis.4

How Prolotherapy Works
Prolotherapy is based on the premise that chronic musculoskeletal pain is caused by an inadequate repair of fibrous connective tissue, resulting in ligament or tendon weakness and relaxation (laxity),also known as connective tissue insufficiency.15 Weak connective tissue results in insufficient tensile strength or tightness,16 causing excessive “loading” of the tissues that stimulates pain mechanoreceptors.15 As long as connective tissue remains functionally insufficient or ineffective, these pain mechanoreceptors continue to fire with use, causing significant pain and limitation of function.17 If the laxity or tensile strength deficit is not corrected sufficiently to stop pain mechanoreceptor stimulation, chronic sprain/strain, and pain results.3

Prolotherapy works by stimulating a temporary, low-grade inflammation at the site of ligament or tendon weakness, “tricking” the body into initiating a new healing cycle cascade.3 A common formula used in classic prolotherapy is dextrose, however, the choice of solution varies depending on practitioner preference and may contain sarapin, morruate, zinc, or other natural ingredients, combined with a local anesthetic.

Platelet-rich Plasma Prolotherapy
In the 1990s, the use of PRP to accelerate healing gained acceptance in surgical circles. However, the machines were large, expensive, and only used in hospital operating rooms. By the 2000s, the machines were smaller and available for use in an office setting.

Prolotherapists, and other physicians in the orthopedic and sports medicine fields, began using PRP injections to stimulate musculoskeletal connective tissue repair.18-20 PRP prolotherapy is based on the same theory as traditional dextrose prolotherapy, however, the formula used is a high-density concentration of the patient’s circulating platelet levels isolated and concentrated by bidirectional centrifugation. Enhanced healing capability is possible when platelet concentrations are increased within injured or damaged tissue.21

High-density PRP (HD-PRP) is defined as autologous blood with concentrations of platelets at no less than four times the circulating baseline levels,22 and which increases the important bioactive protein load (growth factors) in a direct correlative fashion.23 Cell ratios in average circulating whole blood contain only 6% platelets. In true HD-PRP preparations, the concentration achieved is 94%.22 An average patient platelet count is 250,000 platelets/dL. Four times this is 1 million platelets/dL, which is considered the desired benchmark for therapeutic PRP (Figure 1).24

Circulating platelets, when activated, begin a degranulation process that secretes a variety of important growth factors and cytokines/chemokines, such as platelet-derived growth factor (PDGF; stimulates cell replication, angiogenesis), transforming growth factor β-1 (TGF-β1; angiogenesis), vascular endothelial growth factor (VEGF; angiogenesis), fibroblast growth factor (FGF; proliferation of myoblasts and angiogenesis), and insulin-like growth factor-1 (ILGF-1; mediates growth and repair of skeletal muscle), among others.25 Activated platelets also secrete stromal cell–derived factor 1-α (SDF-1α), which supports primary adhesion and migration of mesenchymal stem/stromal cells (Table, page 58).22

Platelets contain a significant number of key signal proteins, growth factors, chemokines, cytokines, and other proinflammatory bioactive factors that initiate and regulate basic aspects of the inflammatory cascade resulting in natural wound healing.26 Elevated platelet concentrations are known to stimulate the proliferation, differentiation, and migration of needed mesenchymal and stromal repair cells to an injury site.27

Similar to dextrose prolotherapy, the addition of HD-PRP concentrates results in an inflammatory and proliferative response that enhances healing and promotes tissue regeneration.28 The use of clinically proven devices to obtain this degree of concentration is considered essential. Various portable commercial centrifugation units exist that can process blood samples, resulting in PRP concentrates, however only a few have been shown to concentrate platelets to therapeutic levels as does the FDA cleared Harvest Technologies’ SmartPrep2 system.

Stem Cell Types
It is believed that there are really only two kinds of stem cells: the embryonic (prenatal) stem cell and the adult (postnatal) stem cell.29 Embyronic stem cells are, in theory, able to transform into any type of tissue; they are totipotent or omnipotent when an egg is fertilized. After several divisions, the stem cell is considered pluripotent, and able to differentiate into any of the three germ layers.30

Postnatal stem cells are those cells present that remain in an individual after birth, in an undifferentiated state, and available to maintain tissue homeostasis and regeneration in a tissue or organ system. Attention to the important potentials of adult stem cells has been discussed in the medical literature since 1963, when Becker et al reported on the regenerative nature of bone marrow.31 These adult stem cells can be activated to proliferate and differentiate to yield some or all of the major specialized cell types of their tissue type when required for maintenance or repair.32 Because they typically differentiate into a variety of cellular phenotypes from one germ layer, they are recognized as multipotent, with some cells demonstrating transdifferentiation capabilities in tissue culture. Multipotent stem cells facilitate tissue maintenance, regeneration, growth, and wound healing throughout life.33 Adult stem cells can be found in all tissues in the body in various quantities.34

Adult Mesenchymal Stem Cells
In the early 1990s, existence of adult mesenchymal stem cells (MSCs), described as “non-committed progenitor cells of musculoskeletal tissues,” were discovered to have an active role in connective tissue repair.35 These cells were first labeled by Caplan as mesenchymal stem cells36 because of their ability to differentiate to lineages of mesenchymal tissue, and were recognized to be an essential component of the tissue repair process.27 An interesting observation made about MSCs is their ability to “home in” and help repair areas of tissue injury.35

Although bone marrow historically has been used as a source of MSCs, adipose-derived MSCs have been shown to have nearly identical fibroblast-like morphology and colonization (CFU-F),
immune phenotype, successful rate of isolation, and differentiation capabilities.37The healing potential of adipose-derived MSCs was demonstrated in early clinical use for cranial defect and chronic fistula repair, without side effects.38 MSCs, along with other cells within the adipose stroma, react to cellular and chemical signals, and have been shown in vitro to differentiate and assist in healing for a wide variety of cellular types. This includes cartilage repair,39 angiogenesis in osteoarthritis,40,41tendon defects,42-44 ligament tissue,45 intervertebral disc repair,46,47 muscle,48nerve tissue,49 bone,50 and hematopoietic-supporting stroma.51 MSCs also actively participate in tissue homestasis, regeneration, and wound healing52; ischemic heart tissue53,54; graft-vs-host disease55; and osteogenesis imperfecta (Figure 2).56

In degenerative diseases, such as osteoarthritis, an individual’s adult stem cell frequency and potency may be depleted, with reduced proliferative capacity and ability to differentiate.57,58 It has been suggested that addition of these missing MSC elements might help these conditions. A number of studies have demonstrated such improvement with adult stem cell therapy by the successful regeneration of osteoarthritic damage and articular cartilage defects.59,60 In 2003, Murphy et al reported significant improvement in medial meniscus and cartilage regeneration with autologous stem cell therapy in an animal model.61 Not only was there evidence of marked regeneration of meniscal tissue, but the usual progressive destruction of articular cartilage, osteophytic remodeling, and subchondral sclerosis commonly seen in osteoarthritic disease was reduced in MSC-treated joints compared with controls.61 In 2008, Centeno et al reported significant knee cartilage growth and symptom improvement in a case report using culture expanded autologous MSCs from bone marrow.62

Multiple studies support the effectiveness of adipose-derived MSCs for use in connective tissue repair, among other potential clinical uses, with more than 40 institutional review board clinical trials ongoing at this time.63 Current FDA restrictions prevent the manipulation or culture expansion of cells, however, they do allow removing cells from an individual and returning them to the same individual during the same procedure.

Historically, MSCs have been studied from bone marrow aspiration. However, bone marrow possesses very few true MSCs, and is gradually being replaced with adipose(fat)-derived stem/stromal cells (AD-SCs) as a primary tissue source.64 Like bone marrow, adipose (fat) tissue is derived from embryonic mesodermal tissue. Fat is a complex tissue that is not only easier to harvest, but offers markedly higher nucleated, undifferentiated stem cell counts65 than bone marrow. Research has shown as much as 500 to 1,000 times as many mesenchymal and stromal vascular stem-like cells exist in adipose as compared with bone marrow (Figure 3, page 60).66-68

In 2001 and 2002, Zuk et al confirmed that adipose stroma contains relatively large numbers of undifferentiated cells capable of producing cartilage, ligament, tendon, muscle, and bone.64,69 AD-SCs also appear to have an increased angiogenic capability versus bone marrow,70 and have been shown to promote neovascularization in skin flaps,71 as well as safely treat depressed scars.72

AD-SCs meet the criteria suggested by Gimble et al that an ideal stem/stromal cell for regenerative medicinal applications should:

• Be found in abundant quanitites;

• Be harvested with a minimally invasive procedure;

• Be differentiated along multiple cell lineage pathways in a regulatable and reproducible manner;

• Be safely and effectively trans-
planted.73,74

Addition of HD-PRP to AD-SC
During the 1990s, further understanding and enhancements to improve the success of fat grafts in cosmetic plastic surgery led to the effective addition of HD-PRP concentrates to these autologous fat grafts (AFG).75-77 It is believed that these effects are largely a result of PRP’s ability to improve active angiogenesis, stimulate and promote undifferentiated cell adherence, proliferation, and differentiation activities of precursor cells in the grafts. Studies have determined the safety and efficacy of implanted/administered AD-SCs and suggest that AD-SC in combination with HD-PRP also can regenerate articular cartilage78 and reverse hip osteonecrosis.79 With high levels of PDGF and cytokines, this combination provides both a living bioscaffold and a multipotent cell replenishment source useful for enhanced musculoskeletal healing.80

Theory of Stem Cell Prolotherapy
The ability of AD-SCs to support and serve as a cell reservoir for connective tissue and joint repair is the basic theory of stem cell prolotherapy. With stem cell prolotherapy, a stem cell niche (microenvironment that favors healing) is moved from one tissue in which these niches are abundant (adipose) into another where they are scarce (a nonrepairing connective tissue).81 Multiple studies have shown that AD-SCs improve wound healing and stimulate fibroblast proliferation, migration, and collagen secretion—thereby increasing connective tissue tensile strength and healing.82

As discussed, AD-SCs have the potential to differentiate to become cartilage, tendon, ligament, bone, and skeletal or smooth muscle. They also are capable of expressing multiple growth factors that influence, control, and manage damaged neighboring cells.83 Additionally, AD-SCs have been reported to be helpful in intervertebral disc regeneration,84 tendon and ligament regeneration,85 and in accelerating tendon repair and strength.86 It is reasonable to hypothesize, therefore, that when traditional dextrose prolotherapy and/or PRP prolotherapy have not resulted in complete resolution of musculoskeletal pain and injury, stem cell prolotherapy would be the logical next step.

In veterinary medicine, AD-SCs have been used effectively for more than 10 years in the treatment of osteoarthritic joints87 and connective tissue injuries in dogs. In fact, in double-blind placebo-controlled trials, AD-SC prolotherapy has be shown to be successful in more than 80% of cases.88

HD-PRP Creates Favorable Growth Factor Environment
A concentrated growth factor environment, coupled with a living bioscaffolding, has been found to be important for AD-SC use in orthopedic applications.89 HD-PRP has shown the ability to enhance musculoskeletal healing and stimulate local microenvironmental regenerative capabilities,80 especially during the early phase of tendon healing.90 Proliferation of AD-SCs and their differentiation also is believed to be directly related to platelet concentration.27 HD-PRP releases large quantities of PDGF, TGF-B1, and many other growth factors that, when activated, significantly enhance stem/stromal cell proliferation and angiogenesis,91-92 as well as enhancing the survival of the fat scaffolding.93

Stem Cell Fate Dependent on
Microenvironment
It is clear that control of cellular fate and extracellular environment is critical in tissue regeneration and cell-based therapies.94 Stem cell fate is controlled by a complex set of physical and chemical signals dictated by the cellular and chemical microenvironment (niche).95 Therefore, if AD-SCs are placed within, and adherent to, damaged connective tissue, uncommitted progenitor and stem/stromal elements within the AD-SC graft should be stimulated toward that specific connective tissue lineage for growth and repair. For example, if placed within osteoarthritic degenerated cartilage, chondrogenic differentiation is believed to be encouraged.96-99

In the 1990s, Young et al showed repair of an Achilles tendon tear when AD-SC was placed in a collagen matrix, then placed in a tendon defect.100 In 2010, Little et al demonstrated the successful differentiation of human AD-SCs to ligament when adipose lipoaspirate was placed in a simulated ligament matrix composed of native ligamentous material combined with collagen fibrin gel. Cells placed in this manner showed changes in gene expression consistent with ligament growth and expression of a ligament phenotype.101 Albano and Alexander successfully reported an autologous fat graft as a mesenchymal stem source and living bioscaffold (termed “Autologous Regenerative Matrix”) to repair a persistent patellar tendon tear.102

Protocol for Stem Cell Prolotherapy
A detailed protocol for stem cell prolotherapy was discussed in the August 2011 issue of the Journal of Prolotherapy.103 A simple means for harvesting adipose tissue is detailed using the patented Tulip MedicalTM microcannula system, which harvests cells and stroma in a safe and nontraumatic manner, preserving the mesenchymal stem/stromal cell elements.104 Lipoaspirates are decanted by gravity, or low g-centrifugation (<1,000×g for 3 minutes), and combined with highly concentrated PRP obtained via Harvest Technologies’ SmartPrep2 system. The combination of PRP and AD-SC in a fat graft matrix is then accurately injected into injured musculoskeletal and connective tissue via ultrasound-guided injection.103

In a trial series of patients, favorable outcomes were noted (reduced pain, improved function) with regenerative repair of ligament and tendon tears and defects in those patients, documented by musculoskeletal ultrasound. The determination of whether to start a patient with dextrose prolotherapy versus PRP versus stem cell prolotherapy is based on the severity of the physical findings in combination with patient preference. This is addressed in the treatment algorithm (Figure 4. page 61).

Conclusion
Prolotherapy has come a long way since those early days in the 1930s when Dr. Gedney injected his own injured and painful thumb, searching for a way to get his body to do what all bodies are programmed to do: heal and regenerate. Prolotherapy is, in fact, the original musculoskeletal “regenerative medicine.” Traditional dextrose prolotherapy is still used with a high success rate in various musculoskeletal complaints. However, should dextrose prolotherapy fail or plateau, HD-PRP prolotherapy can be used to further enhance the healing process. Should HD-PRP prolotherapy fail or plateau, autologous AD-SCs combined with HD-PRP concentrates have proven very effective in the several thousand successful injections in preclinical use by physicians in the United States and elsewhere. HD-PRP prolotherapy and/ or stem cell prolotherapy also can be used as a starting point treatment in more difficult cases.

 

Adipose tissue effectively delivers a living bioscaffold of adult mesenchymal-directed stem and stromal cells to devitalized tissue. The addition of HD-PRP concentrates to the adipose cells enhances healing capabilities and cellular repair. Although multiple articles have shown the benefit of mesenchymal and stromal stem cells in cosmetic plastic surgery and orthopedic surgery, there has not been a standardized, effective protocol addressing an outpatient, bedside procedure for the prololotherapist, sports medicine, regenerative medicine, or orthopedic physician until recently. However, now these protocols are available and being used to obtain documented successful patient outcomes. Recent protocols can be completed at the point of care within the outpatient office setting and do not violate current FDA guidelines.

Outcomes and evidence so far is encouraging and positive, however, as this science continues to grow, more research needs to be done to refine these techniques and provide larger patient trials and longer term outcomes.

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Platelet-Rich Plasma Prolotherapy for Low Back Pain Caused by Sacroiliac Joint Laxity

Past medical history included previous mild scoliosis documented at the T3 level, premenstrual syndrome, and fractures of the left first and second toes. She was a non-smoker, drank alcohol occasionally and ate a mostly vegetarian diet. Her NRS pain 7/10; SFMcGill 23/45; and Oswestry 36/50. Pain was in the midline lower lumbar and parasacral region with radiation into both groins and down the left lateral thigh. Sitting and standing tolerance was limited to 5 to 15 minutes. Physical exam revealed a height of 5’1” and weight 148 lbs. BP 101/67mm Hg. Pulse 84bpm. Straight leg raising was limited to 75 degrees on the left with back pain (no sciatica). Maneuvers of the SI joints provoked pain (including Patrick’s, Faber, Gaenslen, Gillett, Yeomen and shear tests), primarily on the left side. Stability testing revealed 2+ instability in the left SI joint.

She underwent PRPP injections to the left SI joint (Hackett’s B and C points) with 15% dextrose (July 29, 2008—complicated by increased pain which was treated with traumeel-marcaine injections into the piriformis muscles) and then with sodium morrhuate (Hackett’s A,B,C and L4-5 facets, interspinous ligaments for five sessions on Aug. 19, Oct. 14, Nov. 4, Dec. 9, 2008, Feb. 10, 2009) with good results and improved stability. NRS was down to 3/10 and she felt 80% improved. Unfortunately, this was all set back when she was rear-ended in a car accident on April 25, 2009 with NRS pain back up to 7/10. Her right SI joint (foot on brake side) was 3+ unstable. Whitmore-Gordons score 41/60. She received approval from the insurer for PRPP and this was administered on July 14, 2009 (Rt. Hackett’s A, B, C points and L4-5 interspinous and facet ligaments) and repeated on the left side Sept. 18, 2009 (in which additional PRPP to the C6-7 facets also helped to resolve the post-MVA neck pain). Her low back pain measures on March 2010 (6 months post-PRPP) were NRS 1.5/10; SFMcGill 2/45; and Oswestry 4/50. She successfully got married, graduated from naturopathic college and returned back to full activity and sport (pool and weight exercises, cross country skiing).

Appendix A.
Whitmore-Gordons Sacroiliac Instability Tool
Please circle ONE number corresponding to the statement in EACH question that BEST describes your low back pain.
Never Rarely Sometimes Occasional Often Always
1. I have pain in my buttock.
0 1 2 3 4 5
2. My back feels unstable.
0 1 2 3 4 5
3. I get pain (in the low back-buttock area) when I turn in bed.
0 1 2 3 4 5
4. I get pain (same area) when I get out of a low chair.
0 1 2 3 4 5
5. I get pains (same area) when I bend the leg up (such as to put on my sock).
0 1 2 3 4 5
6. I get pain (same area) when going up or down stairs.
0 1 2 3 4 5
7. I feel clicking/ clunking/ popping (same area) when I move.
0 1 2 3 4 5
8. I have had the following injuries to my low back:
___ a) motor vehicle accident with foot on brake at time of impact (score as 5)
___ b) fall on the same buttock or hip (score as 5)
___ c) women: pregnancy-related pelvic pain (score as 5)
___ c) men: unexplained pain (normal urology studies) referred into the testicle (score as5)
___ d) temporary relief with spinal manipulation or sacroiliac belt (score as 5)
___ e) sports or work-related twisting-lifting injury—e.g., bowling, figure skating, etc. (score as 3)
___ f) history of hypermobile “loose” joints (score as 2)
Total Score ____/60


Scoring: Preliminary data on consecutive patients suggests a score over 30 has a sensitivity of 85% and specificity close to 100% (with exclusion of fibromyalgia patients) in correlating with an unstable sacroiliac joint that would respond to the PRP prolotherapy treatment.43 (This is to be further studied with multivariate logistic stepwise regression analysis on a larger number of patients.)

Conclusion

These case studies suggest a role for PRP prolotherapy in the management of chronic low back pain—particularly in those with sacroiliac joint pain and instability. Such cases studies and the newly-described screening tool need to be validated with more research, including double-blind randomized controlled trials.

Acknowledgements

Special thanks to the multidisciplinary team at the Canadian Centre for Integrative Medicine: Scott Whitmore, BScPT, FCAMT; Gordon Lawson, MSc, DC; Mark Tsai, MScPT, FCAMT; Thomas Hein, BScPT, FCAMT; Rob McDonald, BSc, RMT DiplOsteo; Kevin Ho, RN, DC; Leigh Arseneau, BSc, ND; Melanie Eitel, RMA; and Rebecca Chau, RNA.

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Platelet-Rich Plasma Prolotherapy for Low Back Pain Caused by Sacroiliac Joint Laxity in Sarasota Florida

A relatively new treatment modality, PRP prolotherapy demonstrates effectiveness in case studies of patients with sacroiliac joint ligament laxity and painful dysfunction.

The sacroiliac joints are subject to con-siderable stresses in weight-bearing and back-twisting movements. Trauma to the SI ligaments can occur with falls on the buttocks, car accidents, twisting and lifting injuries, and repetitive impact loading from excessive running (marathoners). Predisposing factors include hypermobile joint syndromes (such as Ehlers-Danlos syndrome; see Figure 1) and pregnancy resulting in hormonally induced laxity (relaxin). With an injury to the SI joint, pain tends to be unilateral and can refer to the posterior thigh, iliac fossa and buttocks. Sprains of the iliolumbar ligaments can also result in referred pain into the groin and genitalia. Non-traumatic causes of SI joint pain also include seronegative arthritides such as ankylosing spondylitis, reiter’s syndrome, and psoriatic arthritis.

SI joint ligament instability pain is aggravated with prolonged immobility—e.g., pain from the “cocktail party”-prolonged standing; “theatre”-prolonged sitting. Pain is often worse with turning in bed, getting out of bed, standing up from a seated position or stepping up with the affected leg. Clinical signs include contranutation (anterior torsion of the ilium relative to the sacrum) as reflected by the anterior superior iliac spine (ASIS) being lower and the posterior superior iliac spine (PSIS) being higher. Nutation is the opposite (as when doing the “pelvic tilt”). Provocative tests can be done supine (gapping test, femoral shear test, Laguere’s sign, Gaenslen’s test); prone (sacral apex pressure test, yeoman’s test, posterior iliac glide test); sitting (piedallu sign, supine-to-sit test); and standing (gillet’s knee-to-chest test). Clinical exam for diagnosis is, however, quite unreliable.1,2

A new scale to diagnose SI joint instability that responds to prolotherapy has been recently co-developed by the author and is undergoing validity/reliability testing (Whitmore-Gordons Sacroiliac Instability Tool; see Appendix A). SI joint dysfunction diagnosed by intra-articular blocks accounts for about 20% of chronic low back pain.3,4 Treatment options for SI joint pain include medication (anti-inflammatories, analgesics, cortisone injections), physiotherapy, psychological counseling, surgery (radiofrequency den-ervation, surgical fusion), cortisone and botulinum toxin-A injections,5 and prolotherapy.6 Prolotherapy injections with Platelet-rich Plasma (PRP) is a relatively new treatment. This paper documents its effective application in patients with SI joint ligament laxity and painful dysfunction.

Figures 1A-1C. Signs of Ehlers-Danlos Syndrome. Figures 1a and 1b demonstrate hypermobile joints, and figure 1c demonstrates elastic skin.

It used to be thought (and sometimes is still taught) that there is no movement in the sacroiliac joints. Over 100 years ago, clinical observations documented SI joint movement in pregnant women with low back pain.8 Subsequent in-vivo studies using implanted metal markers and stereoradiography have shown small move-ments in normal individuals in prone hyperextension (2 degrees of backward rotation of the sacrum relative to the ileum; 0.2 degrees of inward rotation of the iliac crests; and translation gliding of 0.6mm between the sacrum and ilium).9Movements were 30-40% smaller in men and tended to increase slightly with age. Larger angular rotations (6-8 degrees) and translations (2.5mm) were reported in one subject with recurrent SI problems.10 In-vitro cadaver studies using embedded lead spheres and CT scan analysis have also documented movement.11Application of eccentric forces (up to 60% of body weight) to cadaver pelvises resulted in rotational and translation movement. Rotational movement was increased by 10% when the posterior or anterior ligaments were cut and by 30% when both were cut.12 Anteriorly, the symphysis pubis is a cartilaginous joint with an interpubic fibrocartilaginous disc between the two joint surfaces. The sacrococcygeal joint is another symphysis that is united by a fibrocartilaginous disc. Occasionally this joint is synovial and movable. With advanced age, this and the SI joint may fuse and become obliterated.

Prolotherapy Background

Prolotherapy is a medical procedure that involves the injection of proliferating agents such as 12.5% dextrose mixed with local anesthetic. The injections are di-rected into ligaments, particularly at their insertion into bone/joints. Stronger customized solutions to promote faster healing include P2G (phenol-glycerine-glucose), sodium morrhuate (cod liver oil extract) and a patient’s own blood (platelet enriched plasma). The goal of prolotherapy is to stimulate collagen formation and deposition. By doing so, ligaments are strengthened and joint stability is enhanced. Such strengthening has been supported by both animal and human studies.13-15

The first physician to report on prolotherapy was Earl Gedney, DO, in 1937, who reported on this type of joint-injection after using it successfully on his own thumb.16At a later date, while performing a hernia operation, general surgeon George Hackett, MD, discovered by chance that injections given “(usually in error) at the junction of ligament and bone resulted in profuse proliferation of new tissue at this union.” He then spent the rest of his career developing and refining the injection techniques leading to the publication of his text Ligament and Tendon Relaxation Treated by Prolotherapy in 1956. He treated 543 chronic low back pain patients (ages 15 to 88 with pain duration of 4 to 56 years) and reported an 82% success rate with such patients considering themselves cured over periods ranging up to 12 years at follow-up. Subsequent supportive clinical studies include case series for chronic groin pain,17 whiplash,18 fibromyalgia19 and randomized controlled trials (RCTs) for knee osteoarthritis,20 finger-thumb osteoarthritis,21 and chronic low back pain.22,23 One two-year RCT for low back pain found improvement in both the active (dextrose) and placebo (saline) prolotherapy groups suggesting that even the needle itself has an effect.

Platelet-Rich Plasma Prolotherapy

Platelet-rich plasma prolotherapy (PRPP) involves the injections of autologous blood—in particular, the portion concentrated with platelets—back into the donor’s body at the site of concern.

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