Yang Jiqiao, Zhou Chen, Fu Jingyang, Yang Qianru, He Tao, Tan Qiuwen, Lv Qing
Department of Breast Surgery, West China Hospital, Sichuan University, Chengdu, China.
Laboratory of Tumor Targeted and Immune Therapy, Clinical Research Center for Breast Disease, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University, Chengdu, China.
Front Cell Dev Biol. 2021 Mar 8;9:647149. doi: 10.3389/fcell.2021.647149. eCollection 2021.
For cosmetic and reconstructive purposes in the setting of small-volume adipose tissue damage due to aging, traumatic defects, oncological resections, and degenerative diseases, the current strategies for soft tissue replacement involve autologous fat grafts and tissue fillers with synthetic, bioactive, or tissue-engineered materials. However, they all have drawbacks such as volume shrinkage and foreign-body responses. Aiming to regenerate bioactive vascularized adipose tissue on biomaterial scaffolds, adipose tissue engineering (ATE) has emerged as a suitable substitute for soft tissue repair. The essential components of ATE include scaffolds as support, cells as raw materials for fat formation, and a tolerant local environment to allow regeneration to occur. The commonly loaded seeding cells are adipose-derived stem cells (ASCs), which are expected to induce stable and predictable adipose tissue formation. However, defects in stem cell enrichment, such as donor-site sacrifice, limit their wide application. As a promising alternative approach, cell-free bioactive scaffolds recruit endogenous cells for adipogenesis. In biomaterials without cell seeds, the key to sufficient adipogenesis relies on the recruitment of endogenous host cells and continuous induction of cell homing to scaffolds. Regeneration, rather than repair, is the fundamental dominance of an optimal mature product. To induce adipogenesis, many researchers have focused on the mechanical and biochemical properties of scaffolds. In addition, efforts to regulate an angiogenic and adipogenic microenvironment in cell-free settings involve integrating growth factors or extracellular matrix (ECM) proteins onto bioactive scaffolds. Despite the theoretical feasibility and encouraging results in animal models, few of the reported cell-free biomaterials have been tested in humans, and failures of decellularized adipose tissues in adipogenesis have also been reported. In these cases, the most likely reason was the lack of supporting vasculature. This review summarizes the current status of biomaterials without cell seeds. Related mechanisms and influencing factors of adipogenesis in cell-free biomaterials, dilemma in the development of biomaterials, and future perspectives are also addressed.
对于因衰老、创伤性缺损、肿瘤切除和退行性疾病导致的小体积脂肪组织损伤的美容和重建目的，目前软组织替代的策略包括自体脂肪移植以及使用合成材料、生物活性材料或组织工程材料的组织填充剂。然而，它们都有诸如体积收缩和异物反应等缺点。旨在在生物材料支架上再生具有生物活性的血管化脂肪组织，脂肪组织工程（ATE）已成为软组织修复的合适替代方法。ATE的基本组成部分包括作为支撑的支架、作为脂肪形成原料的细胞以及允许再生发生的宽容局部环境。常用的接种细胞是脂肪来源干细胞（ASC），期望其能诱导稳定且可预测的脂肪组织形成。然而，干细胞富集方面的缺陷，如供体部位牺牲，限制了它们的广泛应用。作为一种有前景的替代方法，无细胞生物活性支架招募内源性细胞进行脂肪生成。在没有细胞种子的生物材料中，充分脂肪生成的关键在于招募内源性宿主细胞并持续诱导细胞归巢到支架上。再生而非修复是最佳成熟产品的根本优势。为了诱导脂肪生成，许多研究人员专注于支架的机械和生化特性。此外，在无细胞环境中调节血管生成和脂肪生成微环境的努力包括将生长因子或细胞外基质（ECM）蛋白整合到生物活性支架上。尽管在动物模型中有理论可行性和令人鼓舞的结果，但报道的无细胞生物材料中很少有在人体中进行测试的，并且脱细胞脂肪组织在脂肪生成方面的失败也有报道。在这些情况下，最可能的原因是缺乏支持性脉管系统。本综述总结了无细胞种子生物材料的现状。还讨论了无细胞生物材料中脂肪生成的相关机制和影响因素、生物材料开发中的困境以及未来展望。
