Biomimetic injectable HUVEC-adipocytes/collagen/alginate microsphere co-cultures for adipose tissue engineering

• Published in: Biotechnology and bioengineering Vol. 110; no. 5; pp. 1430 - 1443
• Main Authors: Yao, Rui, Zhang, Renji, Lin, Feng, Luan, Jie
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 01.05.2013; Wiley Subscription Services, Inc
• Subjects: Adipocytes - cytology; adipose tissue engineering; Alginates - chemistry; Alginates - pharmacology; Analysis of Variance; Animals; biomimetic; Biomimetic Materials - chemistry; Biomimetic Materials - pharmacology; Blood vessels; Cell Proliferation - drug effects; Cells; Cells, Cultured; Coculture Techniques - methods; Collagen; Collagen - chemistry; Collagen - pharmacology; collagen/alginate; Glucuronic Acid - chemistry; Glucuronic Acid - pharmacology; Hexuronic Acids - chemistry; Hexuronic Acids - pharmacology; Human Umbilical Vein Endothelial Cells - cytology; Humans; Mice; Mice, Inbred BALB C; Mice, Nude; Microspheres; Neovascularization, Physiologic - physiology; Rats; Rodents; Surface Properties; Tissue engineering; Tissue Engineering - methods; vascularization
• ISSN: 0006-3592; 1097-0290
• DOI: 10.1002/bit.24784

Engineering adipose tissue that has the ability to engraft and establish a vascular supply is a laudable goal that has broad clinical relevance, particularly for tissue reconstruction. In this article, we developed novel microtissues from surface‐coated adipocyte/collagen/alginate microspheres and human umbilical vein endothelial cells (HUVECs) co‐cultures that resembled the components and structure of natural adipose tissue. Firstly, collagen/alginate hydrogel microspheres embedded with viable adipocytes were obtained to mimic fat lobules. Secondly, collagen fibrils were allowed to self‐assemble on the surface of the microspheres to mimic collagen fibrils surrounding the fat lobules in the natural adipose tissue and facilitate HUVEC attachment and co‐cultures formation. Thirdly, the channels formed by the gap among the microspheres served as the room for in vitro prevascularization and in vivo blood vessel development. The endothelial cell layer outside the microspheres was a starting point of rapid vascular ingrowth. Adipose tissue formation was analyzed for 12 weeks at 4‐week intervals by subcutaneous injection into the head of node mice. The vasculature in the regenerated tissue showed functional anastomosis with host blood vessels. Long‐term stability of volume and weight of the injection was observed, indicating that the vasculature formed within the constructs benefited the formation, maturity, and maintenance of adipose tissue. This study provides a microsurgical method for adipose regeneration and construction of biomimetic model for drug screening studies. Biotechnol. Bioeng. 2013; 110: 1430–1443. © 2012 Wiley Periodicals, Inc. Biomimetic microtissues composed of surface‐coated adipocyte/collagen/alginate microspheres and HUVECs co‐cultures were developed in this paper. These co‐cultures contained both a tissue element and a vascularization element and highly resembled the components, distribution and structure of natural adipose tissue. Subcutaneous injection into the node mice suggested vascularized adipose tissue formation with functional anastomosis and long‐term stability of volume and weight, indicating that the vasculature formed within the constructs benefited the formation, maturity and maintenance of adipose tissue.