自愈水凝胶
骨骼肌
纤维化
透明质酸
肌肉组织
化学
炎症
生物医学工程
肿胀 的
再生(生物学)
生物相容性
外科
医学
解剖
病理
内科学
细胞生物学
生物
有机化学
作者
Emily J. Su,Christopher Kennedy,Emmanuel Enrique Vega-Soto,Brooke Pallas,Samantha N Lukpat,Do-Yon Hwang,David William Bosek,Celeste Elise Forester,Claudia Loebel,Lisa M. Larkin
出处
期刊:Tissue Engineering Part A
[Mary Ann Liebert]
日期:2023-12-20
标识
DOI:10.1089/ten.tea.2023.0240
摘要
Volumetric Muscle Loss (VML) is the loss of skeletal muscle that exceeds the muscle’s self-repair mechanism and leads to permanent functional deficits. In a previous study, we demonstrated the ability of our scaffold free, multi-phasic, tissue-engineered skeletal muscle units (SMUs) to restore muscle mass and force production. However, it was observed that the full recovery of muscle structure was inhibited due to increased fibrosis in the repair site. As such, novel biomaterials such as hydrogels (HG) may have significant potential for decreasing the acute inflammation and subsequent fibrosis, as well as enhancing skeletal muscle regeneration following VML injury and repair. The goal of the current study was to assess the biocompatibility of commercially available poly(ethylene glycol) (PEG), methacrylated gelatin (GelMA), and hyaluronic acid (HA) hydrogels in combination with our SMUs to treat VML in a clinically relevant large animal model. An acute 30% VML injury created in the sheep peroneus tertius (PT) muscle was repaired with or without hydrogels and assessed for acute inflammation (incision swelling) and WBC counts in blood for 7 days. At the 7-day time point, HA was selected as the HG to use for the combined HG/SMU repair, as it exhibited a reduced inflammation response compared to the other hydrogels. Six weeks after implantation, all groups were assessed for gross and histological structural recovery. The results showed that the groups repaired with an SMU (SMU-Only and SMU+HA) restored muscle mass to greater degree than the groups with only hydrogel and that the SMU groups had PT muscle masses that were statistically indistinguishable from its uninjured contralateral PT muscle. Furthermore, the HA hydrogel, SMU-Only, and SMU+HA groups displayed notable efficacy in diminishing pro-inflammatory markers and showed an increased number of regenerating muscle fibers in the repair site. Taken together, the data demonstrates the efficacy of HA hydrogel in decreasing acute inflammation and fibrotic response. The combination of HA and our SMUs also holds promise to decrease acute inflammation and fibrosis and increase muscle regeneration, advancing this combination therapy towards clinically relevant interventions for VML injuries in humans.
科研通智能强力驱动
Strongly Powered by AbleSci AI