PRP and Regenerative Injection Therapy

The Body as Its Own Pharmacy

When a tissue tears, the first responders are platelets. Within minutes, they aggregate at the wound site and release a cascade of growth factors — PDGF, TGF-beta, VEGF, EGF, IGF-1 — that orchestrate every phase of healing: inflammation, proliferation, and remodeling. Fibroblasts migrate in. New collagen is laid down. Blood vessels sprout. The tissue rebuilds.

Regenerative injection therapy takes this natural healing cascade and concentrates it. Instead of waiting for the body’s dilute circulating repair factors to find a chronically degenerated tendon or arthritic joint, we draw blood, concentrate the healing fraction, and inject it precisely where the damage lives. We are not introducing a foreign drug — we are delivering the patient’s own repair signals, amplified and targeted.

Within the IFM framework, this represents the structural/biomechanical node of the matrix — musculoskeletal integrity, connective tissue health, and the physical architecture that underlies function. Chronic pain, joint degeneration, and tissue failure are not peripheral complaints. They drive sympathetic overdrive, cortisol dysregulation, sleep disruption, and systemic inflammation. Repairing the structure repairs the system.

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Platelet-Rich Plasma (PRP)

Preparation

PRP is autologous — the patient’s own blood, processed chairside.

Procedure:

1. Draw 30-60mL of venous blood into tubes containing anticoagulant
2. Centrifuge to separate components by density: red blood cells (bottom), buffy coat (middle — platelets and white blood cells), platelet-poor plasma (top)
3. Extract the platelet-rich fraction — concentrated platelets suspended in plasma
4. Inject into the target tissue under ultrasound or fluoroscopic guidance for accuracy

Single spin vs. double spin: Single centrifugation is simpler but yields lower platelet concentration and more red blood cell contamination. Double spin (first spin separates RBC; second spin concentrates platelets from plasma) produces higher platelet concentration (4-7x above baseline) and purer product. The evidence increasingly favors higher concentrations for better clinical outcomes.

Leukocyte-rich PRP (LR-PRP) vs. Leukocyte-poor PRP (LP-PRP): This distinction matters clinically. LR-PRP contains neutrophils and monocytes — more inflammatory, more catabolic enzymes (MMPs). Better for chronic tendinopathy (which needs an inflammatory kick to restart healing). LP-PRP has fewer white cells — less inflammatory, better for intra-articular use (joints — where excess inflammation causes damage and pain). The PRP is not one product; it is a spectrum, and preparation method should match the clinical target.

Activation: Platelets can be activated before injection (calcium chloride, thrombin) to trigger immediate growth factor release, or injected without activation — the platelets activate naturally upon contact with exposed collagen in damaged tissue. Most current practice favors non-activated injection, letting the tissue environment control the timing of growth factor release.

Evidence by Indication

Knee Osteoarthritis: The strongest evidence base in regenerative injection medicine. Dai 2017 meta-analysis of 14 RCTs (1,423 patients): PRP was superior to both hyaluronic acid and corticosteroid injection at 12-month follow-up for pain and function in knee OA. The effect was dose-dependent — higher platelet concentrations yielded better outcomes. Filardo 2015 confirmed durability out to 24 months. A 2021 Cochrane review acknowledged moderate evidence for benefit.

Protocol: 1-3 injections, 2-4 weeks apart. LP-PRP preferred for intra-articular injection. Ultrasound-guided for accuracy. Avoid NSAIDs for 2 weeks pre- and post-injection (they suppress the inflammatory healing response that PRP requires). Avoid corticosteroid injection for 6-8 weeks before PRP (corticosteroids are catabolic and blunt the regenerative signal).

Tendinopathy:

• Lateral epicondylitis (tennis elbow): Mishra 2014 RCT — LR-PRP was significantly superior to corticosteroid at 24 weeks and maintained superiority at 2-year follow-up. Corticosteroid provided short-term relief but long-term worsening (corticosteroids weaken tendons). PRP provided sustained healing.
• Achilles tendinopathy: de Vos 2010 — modest benefit; subsequent studies with higher platelet concentrations showed stronger results.
• Patellar tendinopathy (jumper’s knee): Positive case series and emerging RCT data.
• Rotator cuff tendinopathy and partial tears: Growing evidence for pain reduction and functional improvement, potentially reducing need for surgery.

Single injection, can repeat in 6-8 weeks if response incomplete. LR-PRP preferred for tendons. Ultrasound guidance for accuracy. Eccentric loading rehabilitation should accompany PRP — the mechanical stimulus complements the biological signal.

Plantar Fasciitis: Mahindra 2016: PRP superior to corticosteroid at 3 and 12 months. This stubborn condition, where chronic degeneration of the plantar fascia resists conventional treatment, responds to the regenerative stimulus. Single injection under ultrasound guidance into the area of maximum fascial thickening.

Ligament Injuries: ACL partial tears (non-surgical management with PRP showing promising results), chronic ankle instability (lateral ligament complex), sacroiliac ligament laxity.

Muscle Injuries: Hamstring tears, quadriceps strains — PRP at the injury site accelerates return to sport. Emerging evidence in professional athletic settings.

Meniscal Tears: Degenerative partial tears (not bucket handle or locked knee) — intra-articular PRP can reduce symptoms and potentially avoid surgery. LP-PRP injected into the joint bathes the meniscal tear. Not a structural repair but functional improvement sufficient for many patients.

Hair Restoration: Gentile 2015 RCT: PRP scalp injections produced significant increase in hair count, hair density, and terminal hair ratio compared to placebo. Mechanism: growth factors stimulate hair follicle stem cells, prolong anagen phase, improve perifollicular blood supply. Protocol: 3-4 sessions, 4-6 weeks apart, then maintenance every 6-12 months. Comparable results to topical minoxidil in some studies, without daily application.

Skin Rejuvenation (Vampire Facial): PRP combined with microneedling — the microneedles create controlled micro-injuries, PRP delivers concentrated growth factors into the channels. Result: collagen induction, improved skin texture, scar reduction, wrinkle reduction. Evidence: multiple controlled trials show improvement over microneedling alone.

Sexual Health:

• Priapus Shot (P-Shot): PRP injected into the corpus cavernosum for erectile dysfunction (especially mild-moderate, vascular insufficiency) and Peyronie’s disease (scar/plaque reduction). Multiple case series showing improvement. Not FDA-approved but widely performed.
• O-Shot: PRP injected periurethrally and into the anterior vaginal wall for female sexual dysfunction (arousal, orgasm) and stress urinary incontinence. Runels 2014 reported significant improvements. Mechanism: tissue revitalization, nerve regeneration, improved vascularity.

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Prolotherapy: The Foundation of Regenerative Injection

Prolotherapy (proliferative therapy) predates PRP. George Hackett MD developed the technique in the 1950s based on the observation that ligament laxity — loose, stretched-out ligaments — was the unrecognized cause of much chronic musculoskeletal pain.

Mechanism: Injection of an irritant solution (most commonly dextrose at 12.5-25% concentration) into damaged ligament or tendon attachments (entheses). The dextrose provokes a controlled inflammatory response — attracting growth factors, fibroblasts, and initiating collagen deposition. Over weeks, the tissue strengthens. The ligament tightens. The joint stabilizes.

Solutions:

• Dextrose (12.5-25%): The most common and most studied proliferant. Safe, inexpensive, effective.
• P2G (phenol-glucose-glycerin): Stronger irritant for more severely damaged tissue.
• Sodium morrhuate: Fish oil-derived, strong proliferant, less commonly used today.

Best Evidence:

• Sacroiliac and low back pain: Yelland 2004 — dextrose prolotherapy for chronic low back pain showed significant improvement in pain and disability sustained at 24 months.
• Knee osteoarthritis: Rabago 2013 — remarkable study showing that dextrose prolotherapy not only improved knee OA symptoms but INCREASED cartilage thickness on ultrasound at 52-week follow-up. This challenges the dogma that cartilage cannot regenerate.
• Lateral epicondylitis: Multiple positive studies. Scarpone 2008 showed dextrose prolotherapy superior to wait-and-see at 16 weeks.
• Anterior cruciate ligament laxity: Reeves 2003 — prolotherapy decreased anterior-posterior knee laxity measured by KT-1000 arthrometer.

Protocol: Series of 3-6 treatments, spaced 2-4 weeks apart. Multiple injection points targeting the entheses (bone-ligament/tendon junctions) where the tissue is most damaged and where regeneration is needed. Ultrasound guidance increasingly used for accuracy.

Post-injection: Expect 2-5 days of increased soreness (the inflammatory response is the treatment). Avoid NSAIDs and ice (they suppress the desired inflammation). Acetaminophen permitted. Gradual return to activity. The healing response builds cumulatively over the treatment series.

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Prolozone: Prolotherapy Meets Ozone

Frank Shallenberger MD combined prolotherapy principles with ozone therapy and created something that, in many practitioners’ hands, produces faster and more dramatic results than either alone.

Procedure:

1. Inject procaine (local anesthetic) into and around the joint or damaged tissue — provides immediate pain relief and anti-inflammatory effect
2. Inject a nutrient cocktail: hydroxocobalamin (B12), dextrose, and in some protocols, homeopathic anti-inflammatory preparations
3. Inject 10-20mL of O3/O2 gas mixture directly into the joint space or periarticular tissue

Mechanism: The procaine provides immediate analgesia. The ozone increases local oxygen utilization, stimulates fibroblast activity, enhances mitochondrial function in damaged tissue, and modulates local inflammation. The combination restores metabolic function to tissue that has been stuck in a degenerative cycle.

Indications: Osteoarthritis (all joints), chronic joint pain unresponsive to other treatments, disc herniation (intradiscal prolozone — ozone injected directly into the disc), tendinopathy, TMJ dysfunction, chronic low back pain.

Protocol: 3-6 sessions, 2-4 weeks apart. Many patients experience dramatic improvement within 1-3 sessions. Prolozone often works when prolotherapy alone has been insufficient.

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Stem Cell Therapy: Bone Marrow Aspirate Concentrate (BMAC)

The most potent autologous regenerative injection. Bone marrow contains mesenchymal stem cells (MSCs), hematopoietic stem cells, growth factors, and cytokines — the complete repair toolkit.

Procedure:

1. Under local anesthesia and fluoroscopic or ultrasound guidance, aspirate 30-60mL of bone marrow from the posterior iliac crest (hip bone)
2. Process through a centrifuge to concentrate the cellular fraction (BMAC)
3. Inject concentrated BMAC into the target tissue — usually same-day, single procedure

The concentrate contains MSCs that can differentiate into cartilage (chondrogenesis), bone (osteogenesis), tendon, and other connective tissue. But MSCs also exert powerful paracrine effects — they secrete anti-inflammatory cytokines, growth factors, and extracellular vesicles that modulate the local tissue environment even without differentiating.

Indications: Severe osteoarthritis (alternative to joint replacement), avascular necrosis (femoral head — Hernigou 2009 showed BMAC injection delayed or prevented hip replacement), large tendon tears, non-union fractures, cartilage defects.

Regulatory Status (United States): Autologous, same-day, minimally manipulated BMAC is FDA-compliant under 21 CFR 1271 (the “same surgical procedure” exemption). This is different from cultured or expanded stem cells, which require an IND (Investigational New Drug) application. The distinction matters legally and practically.

Combination approach: Many practitioners combine BMAC with PRP — the PRP provides concentrated growth factors that support MSC survival and differentiation. Some add prolotherapy-style dextrose or prolozone to the adjacent ligaments and tendons that stabilize the treated joint. The multimodal approach addresses the joint as an organ, not just the cartilage in isolation.

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Exosome Therapy: The Emerging Frontier

Exosomes are nanoscale extracellular vesicles (30-150nm) secreted by cells — particularly mesenchymal stem cells. They carry a cargo of growth factors, cytokines, mRNA, and microRNA that reprogram recipient cells. Think of them as the emails that stem cells send — the messages that direct repair without the stem cell needing to be physically present.

Sources: Most therapeutic exosomes are derived from Wharton’s jelly (umbilical cord) MSCs or amniotic fluid. They are allogeneic (from donor tissue), not autologous. This eliminates the need for bone marrow harvest.

Administration: IV infusion (systemic) or local injection (into joints, skin, scalp).

Proposed applications: Joint regeneration, neurodegeneration, autoimmune modulation, skin rejuvenation, hair restoration, anti-aging, post-surgical recovery.

Important caveats: Exosome therapy is in its infancy clinically. Product quality varies enormously between manufacturers — particle counts, cargo analysis, sterility testing, and potency assays are not standardized. The FDA has issued warning letters to companies making unsubstantiated claims. Some products marketed as “exosomes” contain minimal actual exosome content.

When the science matures and regulation catches up, exosome therapy may represent the next generation of regenerative medicine — delivering the repair signals without the complexity of living cell transplantation. For now, patients should work with practitioners who source from reputable manufacturers, understand the product they are using, and set realistic expectations.

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Clinical Integration: The Functional Medicine Approach to Musculoskeletal Repair

In the IFM model, a degenerative knee is not just a mechanical failure. It exists within a systemic context. The practitioner asks: What is the inflammatory milieu? Is insulin resistance driving AGE (advanced glycation end-product) accumulation in cartilage? Is the gut leaking endotoxin that feeds systemic inflammation reaching every joint? Are hormonal deficiencies (testosterone, growth hormone, DHEA) depriving tissues of anabolic signals? Is nutritional status adequate — vitamin C for collagen, vitamin D for immune modulation, omega-3s for inflammation resolution?

Regenerative injections work best when the systemic terrain supports healing. A PRP injection into a knee will struggle to repair cartilage if the patient has uncontrolled blood sugar, chronic systemic inflammation, and deficiencies in the cofactors required for tissue repair.

Optimizing outcomes — the pre-injection protocol:

• Resolve insulin resistance (the single most destructive metabolic process for joint health)
• Optimize vitamin D (50-80 ng/mL), vitamin C (2-4g daily), collagen peptides (10-15g daily)
• Address omega-3:omega-6 ratio (anti-inflammatory diet, fish oil 2-4g EPA+DHA)
• Ensure adequate protein intake (1.2-1.6g/kg body weight for tissue repair substrate)
• Discontinue NSAIDs 2 weeks before injection (they suppress the healing response)
• Discontinue corticosteroid injections 6-8 weeks before (catabolic, suppress tissue regeneration)
• Consider BPC-157 peptide therapy (250-500mcg SubQ daily) starting 1-2 weeks before injection to prime the healing environment

Post-injection rehabilitation:

• Protect the treated area for 48-72 hours (no aggressive loading)
• Progressive loading protocol guided by physical therapy starting day 3-7
• Continue collagen, vitamin C, and anti-inflammatory nutrition
• Avoid NSAIDs for 4-6 weeks post-injection
• PBM (red light/NIR therapy) over the treated area enhances regenerative response

The injection is the spark. The systemic environment determines whether that spark catches fire or fizzles. Treat the whole patient, not just the joint.