Department of Biology, University of Rome "Tor Vergata", Rome, 00133, Italy.
PhD Program in Cellular and Molecular Biology, Department of Biology, University of Rome "Tor Vergata", Rome, Italy.
Biol Direct. 2023 Jul 31;18(1):42. doi: 10.1186/s13062-023-00399-1.
Volumetric Muscle Loss (VML), resulting from severe trauma or surgical ablation, is a pathological condition preventing myofibers regeneration, since skeletal muscle owns the remarkable ability to restore tissue damage, but only when limited in size. The current surgical therapies employed in the treatment of this pathology, which particularly affects military personnel, do not yet provide satisfactory results. For this reason, more innovative approaches must be sought, specifically skeletal muscle tissue engineering seems to highlight promising results obtained from preclinical studies in VML mouse model. Despite the great results obtained in rodents, translation into human needs a comparable animal model in terms of size, in order to validate the efficacy of the tissue engineering approach reconstructing larger muscle mass (human-like). In this work we aim to demonstrate the validity of a porcine model, that has underwent a surgical ablation of a large muscle area, as a VML damage model.
For this purpose, morphological, ultrasound, histological and fluorescence analyses were carried out on the scar tissue formed following the surgical ablation of the peroneus tertius muscle of Sus scrofa domesticus commonly called mini-pig. In particular, the replenishment of the damaged area, the macrophage infiltration and the vascularization at different time-points were evaluated up to the harvesting of the scar upon six months.
Here we demonstrated that following VML damage, there is an extremely poor regenerative process in the swine muscle tissue, while the formation of fibrotic, scar tissue occurs. The analyses performed up to 180 days after the injury revealed the development of a stable, structured and cellularized tissue, provided with vessels and extracellular matrix acquiring the status of granulation tissue like in human.
严重创伤或外科消融导致的容积性肌肉损失（VML）是一种阻止肌纤维再生的病理状态，因为骨骼肌具有恢复组织损伤的显著能力，但仅限于一定的大小。目前用于治疗这种特别影响军事人员的病理的外科疗法尚未提供令人满意的结果。因此，必须寻求更具创新性的方法，特别是骨骼肌组织工程似乎从 VML 小鼠模型的临床前研究中获得了有前途的结果。尽管在啮齿动物中取得了巨大的成果，但转化为人类需要在大小方面具有类似的动物模型，以验证组织工程方法在重建更大肌肉质量（类人）方面的疗效。在这项工作中，我们旨在证明经过外科消融较大肌肉区域的猪模型作为 VML 损伤模型的有效性。
为此，对Sus scrofa domesticus（通常称为小型猪）的腓骨第三肌外科消融后形成的瘢痕组织进行了形态学、超声、组织学和荧光分析。特别是，在六个月时收获瘢痕之前，评估了不同时间点受损区域的补充、巨噬细胞浸润和血管化情况。
在这里，我们证明了在 VML 损伤后，猪肌肉组织的再生过程极差，而纤维化、瘢痕组织形成。在损伤后 180 天进行的分析显示，形成了一种稳定、结构和细胞化的组织，具有血管和细胞外基质，获得了类似于人类的肉芽组织状态。
