Savarino L, Baldini N, Greco M, Capitani O, Pinna S, Valentini S, Lombardo B, Esposito M T, Pastore L, Ambrosio L, Battista S, Causa F, Zeppetelli S, Guarino V, Netti P A
Laboratory for Pathophysiology of Orthopaedic Implants, Istituti Ortopedici Rizzoli, Via di Barbiano 1/10, 40136, Bologna, Italy.
Biomaterials. 2007 Jul;28(20):3101-9. doi: 10.1016/j.biomaterials.2007.03.011. Epub 2007 Mar 18.
The ability of a cellular construct to guide and promote tissue repair strongly relies on three components, namely, cell, scaffold and growth factors. We aimed to investigate the osteopromotive properties of cellular constructs composed of poly-epsilon-caprolactone (PCL) and rabbit bone marrow stromal cells (BMSCs), or BMSCs engineered to express bone morphogenetic protein 4 (BMP4). Highly porous biodegradable PCL scaffolds were obtained via phase inversion/salt leaching technique. BMSCs and transfected BMSCs were seeded within the scaffolds by using an alternate flow perfusion system and implanted into non-critical size defects in New Zealand rabbit femurs. In vivo biocompatibility, osteogenic and angiogenic effects induced by the presence of scaffolds were assessed by histology and histomorphometry of the femurs, retrieved 4 and 8 weeks after surgery. PCL without cells showed scarce bone formation at the scaffold-bone interface (29% bone/implant contact and 62% fibrous tissue/implant contact) and scarce PCL resorption (16%). Conversely, PCL seeded with autologous BMSCs stimulated new tissue formation into the macropores of the implant (20%) and neo-tissue vascularization. Finally, the BMP4-expressing BMSCs strongly favoured osteoinductivity of cellular constructs, as demonstrated by a more extensive bone/scaffold contact.
细胞构建体引导和促进组织修复的能力在很大程度上依赖于三个组成部分，即细胞、支架和生长因子。我们旨在研究由聚ε-己内酯（PCL）和兔骨髓基质细胞（BMSC）组成的细胞构建体，或经工程改造表达骨形态发生蛋白4（BMP4）的BMSC的骨促进特性。通过相转化/盐析技术获得了高度多孔的可生物降解PCL支架。使用交替流灌注系统将BMSC和转染的BMSC接种到支架内，并植入新西兰兔股骨的非临界尺寸缺损处。通过对术后4周和8周取出的股骨进行组织学和组织形态计量学评估支架存在所诱导的体内生物相容性、成骨和血管生成作用。不含细胞的PCL在支架-骨界面处显示出稀少的骨形成（29%骨/植入物接触和62%纤维组织/植入物接触）以及稀少的PCL吸收（16%）。相反，接种自体BMSC的PCL刺激新组织长入植入物的大孔（20%）并实现新组织血管化。最后，表达BMP4的BMSC强烈促进细胞构建体的骨诱导性，这通过更广泛的骨/支架接触得以证明。
