皮肤组织工程进化与三维组织打印技术的机遇及挑战

Skin tissue engineering evolution and emerging 3D bioprinting technologies: opportunities and challenges

烧伤和慢性伤口的快速覆盖与愈合仍然是临床待解决的难题,当前主要的治疗方法是皮肤移植及组织工程皮肤替代品覆盖。尽管过去组织工程皮肤的研究已经有很多成果,但许多难题仍未得到解决:比如缺乏血管网络、毛囊、汗腺、皮肤色素细胞等必要的皮肤功能单元。近年来,三维组织打印技术迅速发展,为解决上述难题提供了新思路。但在充分利用该技术之前,相应的种子细胞、生物打印墨水等问题亟待解决,并且要满足医药监管法规的要求,目前该领域中国及国际标准尚未建立。今后的研究应侧重于发掘新型细胞来源、创新生物墨水开发及发展规模化三维打印技术工艺。综述了皮肤组织工程产品的发展,总结现有的种子细胞来源和生物打印墨水材料。重点介绍了三维组织打印工艺的应用,干细胞衍生的种子细胞等用于再塑皮肤功能,支持伤口快速愈合及血管化,推进传统的组织工程制造工艺进入智能机器制造时代。最终利用三维组织打印技术,实现在体外打印与天然皮肤结构和功能相接近的高仿真皮肤。

Burns care and chronic wound healing are two of the most disabling conditions and one major global health burdens.Tissue engineering skin substitutes and skin surgery are the main treatments.Despite the extensive research and development of skin tissue engineering over the last century,challenges remain unsolved,such as delayed vascularization,absence of essential sweat gland units and impaired skin pigmentation.The emerging 3D bioprinting technology is a promise enabling technology to build complex skin constructs.but before this technology can be fully utilized,issues such as seed cells,bio-ink formulations need to be optimized,bioprinting process and 3D printers must satisfy the regulatory requirements,though the national and international standards have yet to be established.Future studies should focus on the development of scalable printable technology,the exploration of novel cell sources and the exploitation of innovative bio-inks.The aim of this review is to provide an update of skin substitute development and application,summarize the available novel cell sources and bio-ink biomaterial with emphasis on their application with 3D printing technology.Especially,the induced pluripotent stem cells and skin progenitor cells in restoring of functions of hair follicles,receptors,sebaceous and sweat glands of skin,supporting rapid vascularization and nerve regeneration,Harness the power of the new emerging 3D printing techniques in skin tissue engineering and move traditional tissue engineering manufacturing process directly into the era of smart manufacturing.Utilizing 3D printing technology to print biologically,structurally and functionally native like artificial skin witch includes all essential cellular components in the near future.