Fischer Eliana O, Tsukerman Anna, Machour Majd, Shuhmaher Margarita, Silverstein Asaf, Yaakov Maya, Bar-Am Orit, Debbi Lior, Levenberg Shulamit
Faculty of Biomedical Engineering, Technion-Israel Institute of Technology, Haifa, 3200003, Israel.
Interdisciplinary Program for Biotechnology Technion-Israel Institute of Technology, Haifa, 3200003, Israel.
Adv Healthc Mater. 2025 May;14(13):e2404542. doi: 10.1002/adhm.202404542. Epub 2025 Jan 31.
Volumetric muscle loss (VML) refers to muscle tissue loss exceeding 20% within a functional area due to trauma or surgery, often leading to physical disabilities. VML treatment relies on the transplantation of autologous flaps harvested from a healthy-donor site while minimizing the probability of immune rejection. However, this approach often leads to donor-site morbidity and relies on a restricted supply of muscle tissue. Current solutions in tissue engineering focus on engineered grafts lacking hierarchical vasculature with a feeding vessel, thus limited by diffusion. This study expanded upon a new approach of multimodal bioprinting which enabled the fabrication of thick hierarchical vascular muscle flaps composed of bioprinted and vascularized skeletal muscle tissue, and a 3D-printed engineered macrovessel, which successfully repaired VML injury in-vivo. The flaps are implanted by anastomosing the macrovessel via microsurgery to the femoral artery in proximity to an induced VML injury in Sprague-Dawley rat hindlimbs. Immediate perfusion of the flaps is demonstrated, as is flap endurance to physiological blood pressure, flow, and shear stress. Flap implantation enhanced myocyte differentiation, and vascular ingrowth and facilitated tissue viability and integration. These results obtained by utilizing human-origin cells provide a foundation for fabricating patient-specific flaps for the treatment of extensive soft tissue defects.
容积性肌肉损失(VML)是指由于创伤或手术导致功能区域内肌肉组织损失超过20%,常导致身体残疾。VML的治疗依赖于从健康供体部位采集的自体皮瓣移植,同时将免疫排斥的可能性降至最低。然而,这种方法常常导致供体部位发病,并且依赖于有限的肌肉组织供应。组织工程中的当前解决方案侧重于缺乏带有供血血管的分层血管系统的工程移植物,因此受到扩散的限制。本研究扩展了一种多模态生物打印的新方法,该方法能够制造由生物打印和血管化骨骼肌组织以及3D打印的工程大血管组成的厚分层血管肌肉皮瓣,其在体内成功修复了VML损伤。通过显微手术将大血管与接近Sprague-Dawley大鼠后肢诱导的VML损伤处的股动脉吻合来植入皮瓣。证明了皮瓣的即时灌注,以及皮瓣对生理血压、血流和剪切应力的耐受性。皮瓣植入增强了肌细胞分化和血管长入,并促进了组织活力和整合。利用人源细胞获得的这些结果为制造用于治疗广泛软组织缺损的患者特异性皮瓣奠定了基础。