Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR, USA.
Knight Campus for Accelerating Scientific Impact, University of Oregon, Eugene, OR, USA.
Biomater Sci. 2024 Oct 8;12(20):5186-5202. doi: 10.1039/d4bm00616j.
Traumatic musculoskeletal injuries that lead to volumetric muscle loss (VML) are challenged by irreparable soft tissue damage, impaired regenerative ability, and reduced muscle function. Regenerative rehabilitation strategies involving the pairing of engineered therapeutics with exercise have guided considerable advances in the functional repair of skeletal muscle following VML. However, few studies evaluate the efficacy of regenerative rehabilitation across the lifespan. In the current study, young and aged mice are treated with an engineered muscle, consisting of nanofibrillar-aligned collagen laden with myogenic cells, in combination with voluntary running activity following a VML injury. Overall, young mice perform at higher running volumes and intensities compared to aged mice but exhibit similar volumes relative to age-matched baselines. Additionally, young mice are highly responsive to the dual treatment showing enhanced force production ( < 0.001), muscle mass ( < 0.05), and vascular density ( < 0.01) compared to age-matched controls. Aged mice display upregulation of circulating inflammatory cytokines and show no significant regenerative response to treatment, suggesting a diminished efficacy of regenerative rehabilitation in aged populations. These findings highlight the restorative potential of regenerative engineering and rehabilitation for the treatment of traumatic musculoskeletal injuries in young populations and the complimentary need for age-specific interventions and studies to serve broader patient demographics.
导致容积性肌肉损失（VML）的创伤性肌肉骨骼损伤，受到不可修复的软组织损伤、受损的再生能力和肌肉功能降低的挑战。涉及将工程治疗方法与运动相结合的再生康复策略，极大地促进了 VML 后骨骼肌的功能修复。然而，很少有研究评估再生康复在整个生命周期中的疗效。在本研究中，年轻和老年小鼠在 VML 损伤后接受一种工程肌肉的治疗，该肌肉由富含成肌细胞的纳米纤维对齐胶原组成，并结合自愿跑步活动。总的来说，年轻小鼠的跑步量和强度比老年小鼠高，但与年龄匹配的基线相比，跑步量相似。此外，年轻小鼠对双重治疗反应非常敏感，与年龄匹配的对照组相比，表现出增强的力量产生（<0.001）、肌肉质量（<0.05）和血管密度（<0.01）。老年小鼠表现出循环炎症细胞因子的上调，并且对治疗没有明显的再生反应，这表明再生康复在老年人群中的疗效降低。这些发现强调了再生工程和康复对于治疗年轻人群创伤性肌肉骨骼损伤的恢复潜力，以及针对特定年龄的干预措施和研究以满足更广泛的患者群体的互补需求。
