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

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‐µl IT injection was administered. Treatments included: saline; 3 µg rhPDGF‐BB; 10 µg rhPDGF‐BB; PRP; and 300 µg 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 µg 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 µg rhPDGF‐BB group relative to saline, PRP, and TCA (p < 0.025). On day 21, maximum load‐to‐rupture was increased in the 10 µg rhPDGF‐BB group relative to saline, PRP, and TCA (p < 0.035) and in the 3 µg rhPDGF‐BB group compared to saline and TCA (p < 0.027). Stiffness in the 10 µg 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 load‐to‐failure (3 and 10 µg) and stiffness (10 µg) relative to controls and commonly used treatments. © 2013 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:145–150, 2014.     

Recombinant human platelet‐derived growth factor BB (rhPDGF‐BB) and beta‐tricalcium phosphate/collagen matrix enhance fracture healing in a diabetic rat model

Diabetes mellitus is a common systemic disease that has been associated with poor fracture healing outcomes. The mechanism through which diabetes impairs bone regeneration is unknown. One possible mechanism may be related to either decreased or uncoordinated release of local growth factors at the fracture site. Indeed, previous studies have found reduced platelet‐derived growth factor (PDGF) levels in the fracture callus of diabetic rats, suggesting that local application of PDGF may overcome the negative effects of diabetes and promote fracture healing. To test this hypothesis, low (22 µg) and high (75 ug) doses of recombinant human PDGF‐BB (rhPDGF‐BB) were applied directly to femur fracture sites in BB Wistar diabetic rats that were then compared to untreated or vehicle‐treated animals. rhPDGF‐BB treatment significantly increased early callus cell proliferation compared to that in control specimens. Low dose rhPDGF‐BB treatment significantly increased callus peak torque values (p < 0.05) at 8 weeks after fracture as compared to controls. High dose rhPDGF‐BB treatment increased callus bone area at 12 weeks postfracture. These data indicate that rhPDGF‐BB treatment ameliorates the effects of diabetes on fracture healing by promoting early cellular proliferation that ultimately leads to more bone formation. Local application of rhPDGF‐BB may be a new therapeutic approach to treat diabetes‐impaired fracture healing. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27: 1074–1081, 2009     

PDGF‐BB inhibits intervertebral disc cell apoptosis in vitro

Degeneration of the intervertebral disc (IVD) results in deterioration of the spinal motion segment and can lead to debilitating back pain. Given the established mitotic and anti‐apoptotic effects of recombinant human platelet‐derived growth factor‐BB (rhPDGF‐BB) in a variety of cell types we postulated that rhPDGF‐BB might delay disc cell degeneration through inhibition of apoptosis. To address this hypothesis, we treated human IVD cells isolated from five independent patients with rhPDGF‐BB in monolayer and 3D pellet cultures. The anti‐apoptotic potential, cell proliferative capacity, morphology/pellet differentiation, and gene expression of PDGF‐treated IVD cells were evaluated via flow cytometry/immunohistochemistry, MTT assays, histology, and quantitative RT‐PCR, respectively. We found that rhPDGF‐BB treatment significantly inhibited cell apoptosis, increased cell proliferation and matrix production, and maintained mRNA expression of critical extracellular matrix genes. This study suggests two possible mechanisms for the anti‐degenerative effects of rhPDGF‐BB on human IVD cells. First, PDGF treatment strongly inhibited IVD cell apoptosis in 3D cultures. Second, rhPDGF‐BB acts as an anabolic agent, promoting maintenance of IVD cell phenotype in 3D culture, based on the molecular and protein expression analysis. We speculate that rhPDGF‐BB may be used as a biologic treatment to target early degenerative IVD disease in the future. © 2014 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 32:1181–1188, 2014.     

Histological and molecular analysis of the biceps tendon long head post‐tenotomy

Tendinopathy is a vexing clinical problem as its onset and development is often asymptomatic and unrecognized until tendon rupture. While extensively studied in the rotator cuff, Achilles, and patellar tendons, no study to date has examined the histological and molecular characteristics of the tendinopathic biceps long‐head (LHB). The anatomy of the LHB is unique in that it comprises intra‐ and extra‐articular portions, each exposed to differing loading patterns. Eleven LHBs post‐tenotomy were sectioned, fixed in formalin, and stained (H&E; Alcian Blue), and gross structural organization of collagen measured using polarized light microscopy. Protein expression of intra‐ and extra‐articular portions of the tenotomized biceps for IGF‐I, collagen III, and MMP‐1, ‐2, ‐3, and ‐13 was determined with Western blot analyses. The intra‐articular LHB exhibited significantly greater histological evidence of tendinopathy inclusive of increased proteoglycan (p < 0.05) and decreased organization as measured by polarized light microscopy (p < 0.01). The intra‐articular LHB also had significantly increased expression of collagen type III (p < 0.01) and of MMP‐1 and 3 (p < 0.01, p < 0.05 respectively). No significant differences were found for IGF‐I or for MMP‐2 and ‐13. The intra‐articular LHB exhibited histological characteristics of tendinopathy. Protein expression of the intra‐articular LHB did not universally display signs of tendinopathy in comparison to the extra‐articular portion of the tendon. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 27:1379–1385, 2009     

Low‐level laser therapy in collagenase‐induced Achilles tendinitis in rats: Analyses of biochemical and biomechanical aspects

NSAIDs are widely prescribed and used over the years to treat tendon injuries despite its well‐known long‐term side effects. In the last years several animal and human trials have shown that low‐level laser therapy (LLLT) presents modulatory effects on inflammatory markers, however the mechanisms involved are not fully understood. The aim of this study was to evaluate the short‐term effects of LLLT or sodium diclofenac treatments on biochemical markers and biomechanical properties of inflamed Achilles tendons. Wistar rats Achilles tendons (n = 6/group) were injected with saline (control) or collagenase at peritendinous area of Achilles tendons. After 1 h animals were treated with two different doses of LLLT (810 nm, 1 and 3 J) at the sites of the injections, or with intramuscular sodium diclofenac. Regarding biochemical analyses, LLLT significantly decreased (p < 0.05) COX‐2, TNF‐α, MMP‐3, MMP‐9, and MMP‐13 gene expression, as well as prostaglandin E₂ (PGE₂) production when compared to collagenase group. Interestingly, diclofenac treatment only decreased PGE₂ levels. Biomechanical properties were preserved in the laser‐treated groups when compared to collagenase and diclofenac groups. We conclude that LLLT was able to reduce tendon inflammation and to preserve tendon resistance and elasticity. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1945–1951, 2012     

Tendon‐derived progenitor cells improve healing of collagenase‐induced flexor tendinitis

Tendinitis is a common and a performance‐limiting injury in athletes. This study describes the value of intralesional tendon‐derived progenitor cell (TDPC) injections in equine flexor tendinitis. Collagenase‐induced tendinitis was created in both front superficial digital flexor (SDF) tendons. Four weeks later, the forelimb tendon lesions were treated with 1 × 10⁷ autogenous TDPCs or saline. Tendinitis was also induced by collagenase in one hind SDF tendon, to study the survival and distribution of DiI‐labeled TDPCs 1, 2, 4, and 6 weeks after injection. The remaining normal tendon was used as a “control.” Twelve weeks after forelimb TDPC injections, tendons were harvested for assessment of matrix gene expression, biochemical, biomechanical, and histological characteristics. DiI‐labeled TDPCs were abundant 1 week after injection but gradually declined over time and were undetectable after 6 weeks. Twelve weeks after TDPC injection, collagens I and III, COMP and tenomodulin mRNA levels were similar (p = 0.3) in both TDPC and saline groups and higher (p < 0.05) than normal tendon. Yield and maximal stresses of the TDPC group were significantly greater (p = 0.005) than the saline group's and similar (p = 0.6) to normal tendon. However, the elastic modulus of the TDPC and saline groups were not significantly different (p = 0.32). Histological assessment of the repair tissues with Fourier transform‐second harmonic generation imaging demonstrated that collagen alignment was significantly better (p = 0.02) in TDPC group than in the saline controls. In summary, treating collagenase‐induced flexor tendon lesions with TDPCs improved the tensile strength and collagen fiber alignment of the repair tissue. Study Design © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:2162–2171, 2016.     

Low‐level laser irradiation promotes cell proliferation and mRNA expression of type I collagen and decorin in porcine achilles tendon fibroblasts In Vitro

Achilles tendon problems are commonly encountered in sports medicine and low‐level laser therapy (LLLT) is widely used in rehabilitative applications to decrease pain, reduce inflammatory processes, and promote tissue healing. This study examined the effects on the proliferation of porcine Achilles tendon fibroblasts and gene expression, using different doses of low‐level laser irradiation (LLLI). Four groups of identically cultured fibroblasts were exposed to LLLI and harvested after 24 h. The control group (Group 1) was subjected to no LLLI. Other groups received 1 J/cm² (Group 2), 2 J/cm² (Group 3), and 3 J/cm² (Group 4), respectively. Cell proliferation and mRNA expressions of type I collagen and decorin were then measured. When compared to the control group, the cell proliferation of irradiated Achilles tendon fibroblasts in the other three groups increased significantly by 13% ± 0.8% (Group 2), 30% ± 0.4% (Group 3), and 12% ± 0.6% (Group 4) respectively. But progressively higher laser intensity did not achieve a correspondingly higher cell proliferation effect in Achilles tendon fibroblasts. The mRNA expressions of decorin and type I collagen in fibroblasts with LLLI were significantly higher (p < 0.05). Therefore, suitable dosages of LLLI may result in more effective tissue healing by promoting type I collagen and decorin synthesis. However, these positive effects of LLLI on the repair of the Achilles tendon in humans should be further investigated in clinic. Published by Wiley Periodicals, Inc. J Orthop Res 27: 646–650, 2009     

Genome‐wide analysis identifies differential promoter methylation of Leprel2, Foxf1, Mmp25, Igfbp6, and Peg12 in murine tendinopathy

We have used a murine Achilles tendinopathy model to investigate whether tissue changes (such as collagen disorganization, chondroid metaplasia, and loss of tensile properties) which are broadly characteristic of human tendinopathies, are accompanied by changes in the expression of chromatin‐modifying enzymes and the methylation status of promoter regions of tendon cell DNA. Tendinopathy was induced by two intra‐tendinous TGF‐β1 injections followed by cage activity or treadmill running for up to 28 days. Activation of DNA methyltransferases occurred at 3 days after the TGF‐β1 injections and also at 14 days, but only with treadmill activity. Genome‐wide Methyl Mini‐Seq™ analysis identified 19 genes with differentially methylated promoters, five of which perform functions with an apparent direct relevance to tendinopathy (Leprel2 , Foxf1 , Mmp25, Igfbp6 , and Peg12) . The functions of the genes identified included collagen fiber assembly and pericellular interactions, therefore their perturbation could play a role in the characteristic disorganization of fibers in affected tendons. We postulate that a study of the functional genomics of these genes in animal and human tendon could further delineate the pathogenesis of this multi‐factorial complex disease. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:947–955, 2017.

     

Use of an IL1‐receptor antagonist to prevent the progression of tendinopathy in a rat model

This study evaluated if inhibiting IL1‐β activity with an IL1‐receptor antagonist (IL1‐RA) will prevent pathologic changes commonly seen in tendinopathy. Thirty‐six Sprague–Dawley retired‐breeder rats were divided into three groups having weekly bilateral patellar tendon injections: CON (0.1 ml Saline), CAR (0.1 ml 2% carrageenan), IL1‐RA (0.1 ml 2% CAR plus 0.94 mg of the IL1‐RA, 2.5 mg/kg). Carrageenan was used to establish tendinopathy in two groups due to its ability to develop tendinopathy in prior studies. Animals were euthanized 3 weeks after initial injection. The CAR group demonstrated significantly (p < 0.05) shorter tendon lengths (8.61 ± 0.38 mm) relative to CON (8.94 ± 0.38 mm) that was prevented in the IL1‐RA (9.02 ± 0.30 mm) as well as significantly increased collagenase activity in the CAR (0.061 ± 0.043) compared to CON (0.027 ± 0.015) (p< 0.05). By histological evaluation, the CAR group demonstrated significantly greater inflammation than IL1‐RA, and CON (p < 0.05). CAR showed a trend for increased cross‐sectional area relative to CON that was absent in the IL1‐RA. IL1‐RA can effectively inhibit the development of mechanical, chemical, and histologic changes seen with carrageenan‐induced tendonitis. © 2015 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 34:616–622, 2016.     

Achilles Impingement Tendinopathy on Magnetic Resonance Imaging

Haglund's syndrome is impingement of the retrocalcaneal bursa and Achilles tendon caused by a prominence of the posterosuperior calcaneus. Radiographic measurements are not sensitive or specific for diagnosing Haglund's deformity. Localization of a bone deformity and tendinopathy in the same sagittal section of a magnetic resonance imaging scan can assist with the diagnosis in equivocal cases. The aim of the present cross-sectional study was to determine the prevalence of Haglund's syndrome in patients presenting with Achilles tendinopathy and note any associated findings to determine the criteria for a diagnosis of Haglund's syndrome. We reviewed 40 magnetic resonance imaging scans with Achilles tendinopathy and 19 magnetic resonance imaging scans with Achilles high-grade tears and/or ruptures. Achilles tendinopathy was often in close proximity to the superior aspect of the calcaneal tuberosity, consistent with impingement (67.5%). Patients with Achilles impingement tendinopathy were more often female (p < .04) and were significantly heavier than patients presenting with noninsertional Achilles tendinopathy (p = .014) or Achilles tendon rupture (p = .010). Impingement tendinopathy occurred medially (8 of 20) and centrally (10 of 20) more often than laterally (2 of 20) and was associated with a posterior prominence or hyperconvexity with a loss of calcaneal recess more often than a superior projection (22 of 27 versus 8 of 27; p < .001). Haglund's deformity should be reserved for defining a posterior prominence or hyperconvexity with loss of calcaneal recess because this corresponds with impingement. Achilles impingement tendinopathy might be more appropriate terminology for Haglund's syndrome, because the bone deformity is often subtle. Of the 27 images with Achilles impingement tendinopathy, 10 (37.0%) extended to a location prone to Achilles tendon rupture. Given these findings, insertional and noninsertional Achilles tendinopathy are not mutually exclusive and impingement might be a subtle, unrecognized cause of Achilles tendinopathy and subsequent rupture.     

ACL reconstruction using bone‐tendon‐bone graft engineered from the semitendinosus tendon by injection of recombinant BMP‐2 in a rabbit model

We attempted to generate a bone‐tendon‐bone structure by injecting human‐type recombinant human bone morphogenetic protein‐2 (rhBMP‐2) into the semitendinosus tendon, and an anterior cruciate ligament (ACL) defect was reconstructed by grafting the engineered bone‐tendon‐bone graft. Two ossicles with a separation distance of 1 cm were generated within the left semitendinosus tendon of a rabbit 6 weeks after the injection of rhBMP‐2 (15 µg at each site). The engineered bone‐tendon‐bone graft was transplanted in order to reconstruct the ACL by passing the graft through the bone tunnels. In the control group, the ACL was reconstructed with the semitendinosus tendon without BMP‐2 using the same methods as those used in the experimental group. The animals were harvested at 4 or 8 weeks after surgery and examined by radiographic, histological, and biomechanical methods. In the experimental group, ossicles in the bone‐tendon‐bone graft were successfully integrated into the host bone of the femur and tibia. Histological analysis revealed that characteristic features identical to the normal direct insertion morphology had been restored. Biomechanical pull‐out testing showed that the ultimate failure load and stiffness of the reconstructed ACL in the experimental group were significantly higher than those in the control group at both 4 and 8 weeks (p < 0.05). These results indicate the potential of regenerative reconstruction of the ACL, and the reconstruction resulted in the restoration of morphology and function equivalent to those of the normal ACL. © 2011 Orthopaedic Research Society Published by Wiley Periodicals, Inc. J Orthop Res 29:1923–1930, 2011     

Enhanced flexor tendon healing through controlled delivery of PDGF‐BB

A fibrin/heparin‐based delivery system was used to provide controlled delivery of platelet derived growth factor BB (PDGF‐BB) in an animal model of intrasynovial flexor tendon repair. We hypothesized that PDGF‐BB, administered in this manner, would stimulate cell proliferation and matrix remodeling, leading to improvements in the sutured tendon's functional and structural properties. Fifty‐six flexor digitorum profundus tendons were injured and repaired in 28 dogs. Three groups were compared: (1) controlled delivery of PDGF‐BB using a fibrin/heparin‐based delivery system; (2) delivery system carrier control; and (3) repair‐ only control. The operated forelimbs were treated with controlled passive motion rehabilitation. The animals were euthanized at 7, 14, and 42 days, at which time the tendons were assessed using histologic (hyaluronic acid content, cellularity, and inflammation), biochemical (total DNA and reducible collagen crosslink levels), and biomechanical (gliding and tensile properties) assays. We found that cell activity (as determined by total DNA, collagen crosslink analyses, and hyaluronic acid content) was accelerated due to PDGF‐BB at 14 days. Proximal interphalangeal joint rotation and tendon excursion (i.e., tendon gliding properties) were significantly higher for the PDGF‐BB‐treated tendons compared to the repair‐alone tendons at 42 days. Improvements in tensile properties were not achieved, possibly due to suboptimal release kinetics or other factors. In conclusion, PDGF‐BB treatment consistently improved the functional but not the structural properties of sutured intrasynovial tendons through 42 days following repair. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res     

Analysis of hereditary and medical risk factors in Achilles tendinopathy and Achilles tendon ruptures: a matched pair analysis

Objective

In Achilles tendon injuries, it is suggested that a pathological continuum might be evident from the healthy Achilles tendon to Achilles tendinopathy to Achilles tendon rupture. As such, risk factors for both tendinopathy and rupture should be the same.

Hypothesis

Hereditary and medical risk factors for Achilles tendinopathy and Achilles tendon rupture are the same to a similar extent in a matched pair analysis.

Design

Matched pair study; level of evidence: 3.

Setting

Recreational sportsmen as well as athletes on national level.

Patients

566 questionnaires were analysed. 310 subjects were allocated to 3 groups (A, B, C) after matching the pairs for age, weight, height and gender: (A) healthy Achilles tendons (n?=?89, age 39?±?11?years, BMI 25.1?±?3.9, females 36%), (B) chronic Achilles tendinopathy (n?=?161, age 41?±?11?years, BMI 24.4?±?3.7, females 34%), (C) acute Achilles tendon rupture (n?=?60, age 40?±?9?years, BMI 25.2?±?3.2, females 27%).

Results

We found a positive family history of Achilles tendinopathy as a risk factor for Achilles tendinopathy (OR: 4.8, 95% CI: 1.1–21.4; p?=?0.023), but not for Achilles tendon rupture (OR: 4.0, 95% CI 0.7–21.1, p?=?0.118). Smoking and cardiac diseases had a lower incidence in Achilles tendinopathy than in healthy subjects (both p?=?0.001), while cardiovascular medication did not change the risk profile.

Conclusion

Identifying risk factors associated with Achilles tendon disorders has a high clinical relevance regarding the development and implementation of prevention strategies and programs. This cross-sectional study identified a positive family history as a significant solitary risk factor for Achilles tendinopathy, increasing the risk fivefold. However, in this matched pair analysis excluding age, weight, height and gender as risk factors no further factor necessarily increases the risk for either Achilles tendinopathy or Achilles tendon rupture.     

Sex matters in the establishment of murine tendon composition and material properties during growth

The existence of sex‐based differences in tendon and ligament injury rates has led investigators to test the hypothesis that sex plays a significant role in modulating tendon and ligament composition and material properties. To date, no studies have attempted to characterize how such differences develop during the course of normal tissue maturation and growth. Thus, the primary aim of the present study was to use a murine model to test the hypothesis that sex‐based differences in the normal age‐related development of tendon composition and material properties exist by assessing these parameters in the Achilles and tail tendons from 4‐, 6‐, 9‐, 12‐, and 15‐week‐old male and female C57Bl/6J mice. Despite significantly lower levels of total collagen content in females subsequent to sexual maturity (p < 0.0001), as well as a significant effect of sex on glycosaminoglycan content (p < 0.0001), Achilles tendon elastic modulus was not compromised in females. Female Achilles tendons did exhibit a significantly higher failure strain (p = 0.0201) and strain energy density (p = 0.0004) than did males, as well as a trend toward higher ultimate strength (p = 0.0556). In contrast to the high load‐bearing environment of the Achilles tendon site, sex did not have a statistically significant effect on any compositional or material property in the low load‐bearing tendon fascicles of the tail. These data support recent studies by others, which suggest that male and female tendons have a differential adaptational response to their local mechanical loading environment. © 2009 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 28:631–638, 2010     

BMP‐2 but not VEGF or PDGF in fibrin matrix supports bone healing in a delayed‐union rat model

Treatment of delayed bone healing and non‐unions after fractures, osteotomies or arthrodesis still is a relevant clinical challenge. Artificially applied growth factors can increase bone healing and progressively gain importance in clinical routine. The aim of this study was to determine the effects of rhPDGF‐BB, rhVEGF‐165, and rhBMP‐2 in fibrin matrix on bone healing in a delayed‐union rat model. Thirty‐seven rats underwent a first operation where a standardized femoral critical size defect was created. A silicone spacer was implanted to impair vascularization within the defect. At 4 weeks the spacer was removed in a second operation and rhPDGF‐BB, rhVEGF‐165, or rhBMP‐2 were applied in a fibrin clot. Animals in a fourth group received a fibrin clot without growth factors. At 8 weeks fibrin bound rhBMP‐2 treated animals showed a significantly increased union rate and bone volume within the defect compared to the other groups. Single application of fibrin bound rhPDGF‐BB and rhVEGF‐165 failed to increase bone healing in our atrophic non‐union model. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 30:1563–1569, 2012     

Accelerated fracture healing in the geriatric,osteoporotic rat with recombinant human platelet‐derived growth factor‐bb and an injectable beta‐tricalcium phosphate/collagen matrix

Aging and osteoporosis contribute to decreased bone mass and bone mineral density as well as compromised fracture healing rates and bone repair quality. Consequently, the purpose of this study was to determine if recombinant human platelet‐derived growth factor‐BB (rhPDGF‐BB) delivered in an injectable beta‐tricalcium phosphate/collagen matrix would enhance tibial fracture healing in geriatric (>2 years of age), osteoporotic rats. A total of 80 rats were divided equally among four groups: Fracture alone; Fracture plus matrix; Fracture plus matrix and either 0.3 mg/mL or 1.0 mg/mL rhPDGF‐BB. At 3 and 5 weeks, rats were euthanized and treatment outcome was assessed histologically, radiographically, biomechanically, and by micro‐CT. Results indicated rhPDGF‐BB‐treated fractures in osteoporotic, geriatric rats caused a statistically significant time‐dependent increase in torsional strength 5 weeks after treatment. The healed fractures were equivalent in torsional strength to the contralateral, unoperated tibiae. Data from the study are the first, to our knowledge, to underscore rhPDGF‐BB efficacy in an injectable beta‐tricalcium phosphate/collagen matrix accelerated fracture repair in a geriatric, osteoporotic rat model. © 2007 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J. Orthop Res 26:83–90, 2008     

Multi‐Scale Loading and Damage Mechanisms of Plantaris and Rat Tail Tendons

Tendinopathy, degeneration of the tendon that leads to pain and dysfunction, is common in both sports and occupational settings, but multi‐scale mechanisms for tendinopathy are still unknown. We recently showed that micro‐scale sliding (shear) is responsible for both load transfer and damage mechanisms in the rat tail tendon; however, the rat tail tendon is a specialized non‐load‐bearing tendon, and thus the load transfer and damage mechanisms are still unknown for load‐bearing tendons. The objective of this study was to investigate the load transfer and damage mechanisms of load‐bearing tendons using the rat plantaris tendon. We demonstrated that micro‐scale sliding is a key component for both mechanisms in the plantaris tendon, similar to the tail tendon. Namely, the micro‐scale sliding was correlated with applied strain, demonstrating that load was transferred via micro‐scale sliding in the plantaris and tail tendons. In addition, while the micro‐scale strain fully recovered, the micro‐scale sliding was non‐recoverable and strain‐dependent, and correlated with tissue‐scale mechanical parameters. When the applied strain was normalized, the % magnitudes of non‐recoverable sliding was similar between the plantaris and tail tendons. Statement of clinical significance: Understanding the mechanisms responsible for the pathogenesis and progression of tendinopathy can improve prevention and rehabilitation strategies and guide therapies and the design of engineered constructs. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:1827–1837, 2019