Dawson Jonathan I, Wahl Denys A, Lanham Stuart A, Kanczler Janos M, Czernuszka Jan T, Oreffo Richard O C
Institute of Developmental Sciences, Mailpoint 887, Southampton General Hospital, Southampton SO16 6YD, UK.
Biomaterials. 2008 Jul;29(21):3105-16. doi: 10.1016/j.biomaterials.2008.03.040. Epub 2008 Apr 28.
Type I Collagen matrices of defined porosity, incorporating carbonate substituted hydroxyapatite (HA) crystals, were assessed for their ability to support osteo- and chondrogenic differentiation of human bone marrow stromal cells (HBMSCs). Collagen-HA composite scaffolds supported the osteogenic differentiation of HBMSCs both in vitro and in vivo as demonstrated by histological and micro-CT analyses indicating the extensive penetration of alkaline phosphatase expressing cells and new matrix synthesis with localised areas immunologically positive for osteocalcin. In vivo, extensive new osteoid formation of implant origin was observed in the areas of vasculature. Chondrogenic matrix synthesis was evidenced in the peripheral regions of pure collagen systems by an abundance of Sox9 expressing chondrocytes embedded within a proteoglycan and collagen II rich ECM. The introduction of microchannels to the scaffold architecture was seen to enhance chondrogenesis. Tissue specific gene expression and corresponding matrix synthesis indicate that collagen matrices support the growth and differentiation of HBMSCs and suggest the potential of this platform for understanding the ECM cues necessary for osteogenesis and chondrogenesis.
对具有特定孔隙率并包含碳酸盐取代羟基磷灰石(HA)晶体的I型胶原蛋白基质,评估其支持人骨髓基质细胞(HBMSC)成骨和软骨分化的能力。组织学和显微CT分析表明,表达碱性磷酸酶的细胞广泛渗透,且有新的基质合成,局部区域骨钙素免疫呈阳性,这证明胶原蛋白-HA复合支架在体外和体内均支持HBMSC的成骨分化。在体内,在血管区域观察到大量源自植入物的新类骨质形成。在纯胶原蛋白系统的周边区域,大量表达Sox9的软骨细胞嵌入富含蛋白聚糖和胶原蛋白II的细胞外基质中,证明了软骨基质的合成。在支架结构中引入微通道可增强软骨形成。组织特异性基因表达和相应的基质合成表明,胶原蛋白基质支持HBMSC的生长和分化,并表明该平台在理解成骨和软骨形成所需的细胞外基质信号方面具有潜力。