Scholp Austin J, Jensen Jordan A, Fowler Timothy P, Petersen Emily, Fredericks Douglas, Salem Aliasger K, Seol Dongrim, Coleman Mitchell, Lake Spencer P, Martin James A, Sander Edward A
Roy J. Carver Department of Biomedical Engineering, University of Iowa, Iowa City, Iowa, USA.
Department of Orthopedics and Rehabilitation, University of Iowa, Iowa City, Iowa, USA.
J Orthop Res. 2025 Jan;43(1):23-36. doi: 10.1002/jor.25967. Epub 2024 Sep 15.
Elbow trauma can lead to joint contracture and reduced range of motion (ROM). Nonsurgical interventions can improve ROM, but in some cases capsule release surgery is required. Although surgery can improve ROM, it often does not restore full ROM. Thus, alternatives are needed. One approach is to target activated myofibroblasts, which are commonly associated with fibrotic tissue. Mechanical and biochemical cues drive a feedback loop that can result in normal or pathological healing. We hypothesize that this feedback loop exists in joint contracture and can be manipulated so that myofibroblast activity is reduced, normal healing is achieved, and ROM is improved. We previously demonstrated that blebbistatin can inhibit myofibroblast contractile forces and reduce collagen synthesis in vitro. Thus, the purpose of this study was to assess the use of blebbistatin in an animal model of elbow contracture, which was induced in 7 groups of 4 rats each (n = 28). All elbows were mechanically and histologically tested. The uninjured contralateral elbows of each rat were used as a control group. Capsule release surgery significantly improved (p < 0.01) outcomes 1 week after surgery compared to injury alone and was not significantly different from uninjured elbows. Three weeks after surgery, outcomes worsened, indicating joint stiffening consistent with what is observed clinically. The addition of blebbistatin did not significantly improve outcomes. Future work will investigate relationships among treatment, fibrotic tissue deposition, myofibroblast activity, and biomechanics to determine if blebbistatin is a useful adjunctive therapy for treating joint contracture.
肘部创伤可导致关节挛缩和活动范围(ROM)减小。非手术干预可改善ROM,但在某些情况下需要进行关节囊松解手术。尽管手术可改善ROM,但通常无法恢复完全的ROM。因此,需要其他替代方法。一种方法是针对活化的肌成纤维细胞,其通常与纤维化组织相关。机械和生化信号驱动一个反馈回路,可导致正常或病理性愈合。我们假设这种反馈回路存在于关节挛缩中,并且可以进行调控,从而降低肌成纤维细胞活性,实现正常愈合并改善ROM。我们之前证明,blebbistatin可在体外抑制肌成纤维细胞的收缩力并减少胶原蛋白合成。因此,本研究的目的是评估blebbistatin在肘部挛缩动物模型中的应用,该模型在7组大鼠中诱导建立,每组4只大鼠(n = 28)。对所有肘部进行了力学和组织学测试。将每只大鼠未受伤的对侧肘部用作对照组。与单纯损伤相比,关节囊松解手术在术后1周显著改善了结果(p < 0.01),且与未受伤的肘部无显著差异。术后3周,结果恶化,表明关节僵硬,这与临床观察结果一致。添加blebbistatin并未显著改善结果。未来的工作将研究治疗、纤维化组织沉积、肌成纤维细胞活性和生物力学之间的关系,以确定blebbistatin是否是治疗关节挛缩的有用辅助疗法。