Comparison of the effect of intra‐tendon applications of recombinant human platelet‐derived growth factor‐BB, platelet‐rich plasma, steroids in a rat achilles tendon collagenase model

Abstract

This study compared the effect of intra-tendon (IT) delivery of recombinant human platelet-derived growth factor-BB (rhPDGF-BB), platelet-rich plasma (PRP) and corticosteroids in a rat tendinopathy model. Seven days after collagenase induction of tendinopathy, a 30-ml IT injection was administered. Treatments included: saline; 3 mg rhPDGF-BB; 10 mg rhPDGF-BB; PRP; and 300 mg triamcinolone acetonide (TCA). Outcomes were assessed 7 and 21 days after treatment. All groups exhibited good to excellent repair. Relative to saline, cell proliferation increased 65% in the 10 mg rhPDGF-BB group and decreased 74% in the TCA group; inflammation decreased 65% in the TCA group. At 7 days, maximum load-to-failure was increased in the 3 mg rhPDGF-BB group relative to saline, PRP, and TCA (p < 0.025). On day 21, maximum load-to-rupture was increased in the 10 mg rhPDGF-BB group relative to saline, PRP, and TCA (p < 0.035) and in the 3 mg rhPDGF-BB group compared to saline and TCA (p < 0.027). Stiffness in the 10 mg rhPDGF-BB group was increased compared to saline, PRP, and TCA (p < 0.038). Histology demonstrated similar repair in all groups. PRP and TCA did not improve mechanical properties compared to saline. Injections of rhPDGF-BB increased maximum loadto-failure (3 and 10 mg) and stiffness (10 mg) relative to controls and commonly used treatments. Keywords: tendinopathy; platelet-derived growth factor-BB; platelet-rich plasma; corticosteroid; biomechanics Tendinopathy is a painful condition that develops as result of tendon degeneration 1,2 and can affect tendons throughout the body (e.g., rotator cuff, Achilles). Tendinopathy leads to collagen degeneration, disorganization, increased mucoid ground substance, proliferation of capillaries and arterioles, loss of mechanical properties, and concomitant pain. These degenerative changes occur without macroscopic tearing of the tendon and may result from a failed healing response to sub-failure injuries. [1][2][3] Current treatment options for tendinopathy including, but not limited to, exercise-based physical therapy, corticosteroid injections, non-steroidal antiinflammatory drugs, extracorporeal shock wave therapy and surgical interventions 4-11 have met varying degrees of success. These therapies often treat the symptoms associated with the condition, but do not address the underlying cause resulting in persistence of the degeneration. While not considered a goldstandard treatment, corticosteroid injections are often administered for chronic tendinopathies. However, there are concerns about the long-term safety and efficacy of this therapy 8-10 due to adverse changes within the tendon. 12 Growth factors have also been assessed to promote tendon healing. Autologous growth factors in the form of platelet-rich plasma (PRP) have been studied; however variability in the preparation and composition of PRP makes it difficult to compare results across studies. 13 Additionally, variable clinical outcomes following PRP treatment for tendinopathy have been reported. 14,15 As an ...

PDGFB-based stem cell gene therapy increases bone strength in the mouse

“…PDGF-BB is a major growth factor found in bone matrix (10) and has also been shown to increase bone formation after intravenous administration (11). In addition, there have been considerable successful applications of PDGF-BB-based therapies on various types of maladies, including tendon, periodontal ligament, and bone fracture repairs (12,13). The safety of PDGF-BB has been demonstrated in several clinical trials (14,15), and it has been approved by the Food and Drug Administration for treatment of patients with oral and maxillofacial bony defects (15).…”

Biologic and Tissue Engineering Strategies for Tendon Repair

“…In a rat model of Achilles tendinopathy, rhPDGF injections significantly increased maximal strength of augmented tendons compared with those treated with saline or PRP. The 3-μg dose increased maximal load to 24.5 ± 4.3 N after 7 days, whereas maximal load of saline-injected controls was 12.5 ± 2.9 N. After 21 days, maximal load for tendons receiving 10 μg PDGF-BB was 30.1 ± 5.5 N compared to 15.7 ± 4.4 N for controls [68]. In an ovine model of rotator cuff repair, bovine collagen matrix scaffolds seeded with rhPDGF at dosages of 75 and 150 μg s i g n i f i c a n t l y i m p r o v e d u l t i m a t e f a i l u r e l o a d s (1490.5 ± 224.5 N and 1486.6 ± 229.0 N respectively vs. 910.4 ± 156.1 N for suture-only controls) [69].…”

“…PRP did not affect the biomechanical properties of Achilles repair in a rat model [68], and PRP-treated flexor-tendon lesions in sheep were found to have elevated Col-1II expression, poorly aligned ECM, and extensive, pathological hypervascularization [85]. Beck et al surgically repaired defects of the supraspinatus tendon-bone interface using transosseus repair methods in a rat model.…”

Biologics in Achilles tendon healing and repair: a review

“…However, the evidence for use in human chronic Achilles tendinopathy remains insufficient [60,50,74,56]. In humans, the use of PRP for Achilles tendinopathy is no more beneficial than the use of placebo treatment or control [67,16,62] Several studies suggesting an improvement of clinical symptoms provide weak evidence with a lack of control groups [20,23,49,51].…”