Fascicular elastin within tendon contributes to the magnitude and modulus gradient of the elastic stress response across tendon type and species.

Elastin, the main component of elastic fibers, has been demonstrated to significantly influence tendon mechanics using both elastin degradation studies and elastinopathic mouse models. However, it remains unclear how prior results differ between species and functionally distinct tendons and, in particular, how results translate to human tendon. Differences in function between fascicular and interfascicular elastin are also yet to be fully elucidated. Therefore, this study evaluated the quantity, structure, and mechanical contribution of elastin in functionally distinct tendons across species. Tendons with an energy-storing function had slightly more elastin content than tendons with a positional function, and human tendon had at least twice the elastin content of other species. While distinctions in the organization of elastic fibers between fascicles and the interfascicular matrix were observed, differences in structural arrangement of the elastin network between species and tendon type were limited. Mechanical testing paired with enzyme-induced elastin degradation was used to evaluate the contribution of elastin to tendon mechanics. Across all tendons, elastin degradation affected the elastic stress response by decreasing stress values while increasing the modulus gradient of the stress-strain curve. Only the contributions of elastin to viscoelastic properties varied between tendon type and species, with human tendon and energy-storing tendon being more affected. These data suggest that fascicular elastic fibers contribute to the tensile mechanical response of tendon, likely by regulating collagen engagement under load. Results add to prior findings and provide evidence for a more mechanistic understanding of the role of elastic fibers in tendon. STATEMENT OF SIGNIFICANCE: Elastin has previously been shown to influence the mechanical properties of tendon, and degraded or abnormal elastin networks caused by aging or disease may contribute to pain and an increased risk of injury. However, prior work has not fully determined how elastin contributes differently to tendons with varying functional demands, as well as within distinct regions of tendon. This study determined the effects of elastin degradation on the tensile elastic and viscoelastic responses of tendons with varying functional demands, hierarchical structures, and elastin content. Moreover, volumetric imaging and protein quantification were used to thoroughly characterize the elastin network in each distinct tendon. The results presented herein can inform tendon-specific strategies to maintain or restore native properties in elastin-degraded tissue.

Pleiotropic Effects of Simvastatin and Losartan in Preclinical Models of Post-Traumatic Elbow Contracture.

Elbow trauma can lead to post-traumatic joint contracture (PTJC), which is characterized by loss of motion associated with capsule/ligament fibrosis and cartilage damage. Unfortunately, current therapies are often unsuccessful or cause complications. This study aimed to determine the effects of prophylactically administered simvastatin (SV) and losartan (LS) in two preclinical models of elbow PTJC: an in vivo elbow-specific rat injury model and an in vitro collagen gel contraction assay. The in vivo elbow rat (n = 3-10/group) injury model evaluated the effects of orally administered SV and LS at two dosing strategies [i.e., low dose/high frequency/short duration (D1) vs. high dose/low frequency/long duration (D2)] on post-mortem elbow range of motion (via biomechanical testing) as well as capsule fibrosis and cartilage damage (via histopathology). The in vitro gel contraction assay coupled with live/dead staining (n = 3-19/group) evaluated the effects of SV and LS at various concentrations (i.e., 1, 10, 100 µM) and durations (i.e., continuous, short, or delayed) on the contractibility and viability of fibroblasts/myofibroblasts [i.e., NIH3T3 fibroblasts with endogenous transforming growth factor-beta 1 (TGFß1)]. In vivo, no drug strategy prevented elbow contracture biomechanically. Histologically, only SV-D2 modestly reduced capsule fibrosis but maintained elevated cellularity and tissue hypertrophy, and both SV strategies lessened cartilage damage. SV modest benefits were localized to the anterior region, not the posterior, of the joint. Neither LS strategy had meaningful benefits in capsule nor cartilage. In vitro, irrespective of the presence of TGFß1, SV (≥10 µM) prevented gel contraction partly by decreasing cell viability (100 µM). In contrast, LS did not prevent gel contraction or affect cell viability. This study demonstrates that SV, but not LS, might be suitable prophylactic drug therapy in two preclinical models of elbow PTJC. Results provide initial insight to guide future preclinical studies aimed at preventing or mitigating elbow PTJC.