Chen David C, Avansino Jeffrey R, Agopian Vatche G, Hoagland Vicki D, Woolman Jacob D, Pan Sheng, Ratner Buddy D, Stelzner Matthias
Department of Surgery, VA Greater Los Angeles Health Care System, University of California at Los Angeles, Los Angeles, Calif 90024, USA.
Cells Tissues Organs. 2006;184(3-4):154-65. doi: 10.1159/000099622.
Biodegradable polyester scaffolds have proven useful for growing neointestinal tissue equivalents both in vitro and in vivo. These scaffolds allow cells to attach and grow in a 3-dimensional space while nutrient flow is maintained throughout the matrix. The purpose of this study was to evaluate different biopolymer constructs and to determine mucosal engraftment rates and mucosal morphology.
We hypothesized that different biopolymer constructs may vary in their ability to provide a good scaffolding onto which intestinal stem cell organoids may be engrafted.
Eight different microporous biodegradable polymer tubes composed of polyglycolic acid (PGA), polylactic acid, or a combination of both, using different fabrication techniques were seeded with intestinal stem cell clusters obtained from neonatal rats. Three different seeded polymer constructs were subsequently placed into the omentum of syngeneic adult recipient rats (n = 8). Neointestinal grafts were harvested 4 weeks after implantation. Polymers were microscopically evaluated for the presence of mucosal growth, morphology, scar formation and residual polymer.
Mucosal engraftment was observed in 7 out of 8 of the polymer constructs. A maximal surface area engraftment of 36% (range 5-36%) was seen on nonwoven, randomly entangled, small fiber PGA mesh coated with aerosolized 5% poly-L-lactic acid. Villous and crypt development, morphology and created surface area were best on PGA nonwoven mesh constructs treated with poly-L-lactic acid. Electrospun microfiber PGA had poor overall engraftment with little or no crypt or villous formation.
Intestinal organoids can be engrafted onto biodegradable polyester scaffoldings with restitution of an intestinal mucosal layer. Variability in polymer composition, processing techniques and material properties (fiber size, luminal dimensions and pore size) affect engraftment success. Future material refinements should lead to improvements in the development of a tissue-engineered intestine.
可生物降解的聚酯支架已被证明在体外和体内培养新肠组织等效物方面很有用。这些支架允许细胞在三维空间中附着和生长，同时在整个基质中维持营养物质流动。本研究的目的是评估不同的生物聚合物构建体，并确定黏膜植入率和黏膜形态。
我们假设不同的生物聚合物构建体在为肠道干细胞类器官提供良好支架以供植入的能力方面可能存在差异。
使用不同制造技术，由聚乙醇酸（PGA）、聚乳酸或两者组合制成的八种不同的微孔可生物降解聚合物管，接种从新生大鼠获得的肠道干细胞簇。随后将三种不同的接种聚合物构建体植入同基因成年受体大鼠（n = 8）的大网膜中。植入后4周收获新肠移植物。通过显微镜评估聚合物中黏膜生长、形态、瘢痕形成和残留聚合物的情况。
在8种聚合物构建体中的7种中观察到黏膜植入。在涂有5%聚-L-乳酸气雾剂的非织造、随机缠结的小纤维PGA网片上，最大表面积植入率为36%（范围为5%-36%）。用聚-L-乳酸处理的PGA非织造网片构建体上的绒毛和隐窝发育、形态及形成的表面积最佳。静电纺丝微纤维PGA总体植入效果差，几乎没有或没有隐窝或绒毛形成。
肠道类器官可以植入可生物降解的聚酯支架上，并恢复肠道黏膜层。聚合物组成、加工技术和材料特性（纤维尺寸、管腔尺寸和孔径）的变化会影响植入成功率。未来材料的改进应会促进组织工程肠道的发展。
