Gombotz W R, Pankey S C, Bouchard L S, Phan D H, Puolakkainen P A
Biological Process Research, Bristol-Myers Squibb, Pharmaceutical Research Institute, Seattle, Washington.
J Appl Biomater. 1994 Summer;5(2):141-50. doi: 10.1002/jab.770050207.
The ability to transforming growth factor-beta 1 (TGF-beta 1), to stimulate bone healing was evaluated in a rat critical calvarial defect model. Both a low dose and a high dose of TGF-beta 1 were incorporated into two different types of implants: one made from a composite of poly(lactic-co-glycolic acid) (PLPG) (50:50) and demineralized bone matrix (DBM), and the other from calcium sulfate (CaSO 4). Scanning electron microscopy showed that the CaSO 4 implants were more porous than the PLPG/DBM samples. Both types of implants released biologically active TGF-beta 1 for over 300 h in vitro. The samples were implanted in a 9-mm diameter rat calvarial defect for 6 weeks along with contralateral control implants containing no TGF-beta 1. Microradiography and histological analysis were used to assess the bone healing in the defects. Microradiography revealed that the greatest amount of calcified bone (67.5%) was present in in the CaSO 4 implants containing a high dose of TGF-beta 1 while minimal new bone formation occurred in the PLPG/DBM implants. Histologically, the PLPG/DBM implants exhibited an inflammatory response with little mineralization or bone formation. The defects containing the PLPG/DBM implants consisted of a connective tissue stroma with large void spaces. Giant cells and numerous polymorphonuclear leukocytes were present throughout the implants. In contrast, the CaSO 4 implants had only a few inflammatory cells and the presence of mineralization and true bone was a more consistent feature. These preliminary studies show that TGF-beta 1 is capable of inducing new bone formation. Furthermore, the materials used to deliver the growth factor can play a significant role in the bone healing process.
在大鼠颅骨临界缺损模型中评估了转化生长因子β1（TGF-β1）刺激骨愈合的能力。将低剂量和高剂量的TGF-β1分别掺入两种不同类型的植入物中：一种由聚（乳酸-共-乙醇酸）（PLPG）（50:50）与脱矿骨基质（DBM）的复合材料制成，另一种由硫酸钙（CaSO₄）制成。扫描电子显微镜显示，CaSO₄植入物比PLPG/DBM样品的孔隙更多。两种类型的植入物在体外均能释放生物活性TGF-β1超过300小时。将这些样品与不含TGF-β1的对侧对照植入物一起植入直径9毫米的大鼠颅骨缺损处6周。使用显微放射摄影和组织学分析来评估缺损处的骨愈合情况。显微放射摄影显示，在含有高剂量TGF-β1的CaSO₄植入物中存在最多的钙化骨（67.5%），而PLPG/DBM植入物中几乎没有新骨形成。组织学上，PLPG/DBM植入物表现出炎症反应，矿化或骨形成很少。含有PLPG/DBM植入物的缺损由具有大空隙的结缔组织基质组成。整个植入物中都有巨细胞和大量多形核白细胞。相比之下，CaSO₄植入物只有少量炎症细胞，矿化和真骨的存在是更一致的特征。这些初步研究表明，TGF-β1能够诱导新骨形成。此外，用于递送生长因子的材料在骨愈合过程中可以发挥重要作用。
