Nathan R M, Bentz H, Armstrong R M, Piez K A, Smestad T L, Ellingsworth L R, McPherson J M, Seyedin S M
Connective Tissue Research Laboratories, Collagen Corporation, Palo Alto, California 94303.
J Orthop Res. 1988;6(3):324-34. doi: 10.1002/jor.1100060304.
Subcutaneous (S.C.) implantation of allogeneic demineralized bone matrix in rats results in endochondral bone formation. In contrast, implants of bovine demineralized bone matrix in rat S.C. tissue show inconsistent cartilage and bone formation, presumably due to an intense inflammatory reaction at the implant site. To overcome this response, a partially purified bone inducing extract was prepared from bovine bone by a series of steps that included demineralization, guanidine/HCl extraction, gel filtration, and cation exchange chromatography. To develop a carrier, the inactive guanidine/HCl-extracted matrix was then trypsinized to remove the inflammatory and immunogenic components, thus yielding a predominantly collagenous matrix. Bovine composites were prepared by combining different amounts of the bone inducing extract with a carrier that consisted of the trypsinized bone matrix and purified soluble bovine dermal collagen. Subcutaneous implantation of the composite preparation resulted in dose-dependent endochondral bone formation in rats. The inductive activity and the low-level inflammatory response were comparable to allogeneic implants.
在大鼠皮下(S.C.)植入同种异体脱矿骨基质会导致软骨内成骨。相比之下,将牛脱矿骨基质植入大鼠皮下组织时,软骨和骨形成情况不一致,推测这是由于植入部位发生强烈的炎症反应所致。为克服这种反应,通过一系列步骤从牛骨中制备了一种部分纯化的骨诱导提取物,这些步骤包括脱矿、胍/盐酸提取、凝胶过滤和阳离子交换色谱法。为开发一种载体,将无活性的胍/盐酸提取的基质用胰蛋白酶处理以去除炎症和免疫原性成分,从而得到主要为胶原质的基质。通过将不同量的骨诱导提取物与由经胰蛋白酶处理的骨基质和纯化的可溶性牛真皮胶原组成的载体相结合,制备了牛复合材料。将该复合制剂皮下植入大鼠后,会导致大鼠软骨内成骨呈剂量依赖性。其诱导活性和低水平炎症反应与同种异体植入物相当。