CRANIOFACIAL BONE REGENERATION IN PRIMATES BY BMPS

描述（改编自研究者摘要）：最近 分离和表征的骨形态发生蛋白（BMP）诱导 体内软骨内骨分化。 分子克隆和 人重组骨形成蛋白的表达可能提供了 控制启动骨再生和修复的人。而 在分子的阐明方面正在取得实质性进展， 以及涉及BMP诱导的骨分化的细胞机制， BMP的形态发生潜能主要基于以下工作： 建议研究的长远目标是研究 天然和重组BMP的有效性和安全性 在非人类灵长类动物模型中的携带者。 这项工作与 先天性和获得性颅颌面骨的修复和再生 申请人建议调查其功效， 天然和重组骨形态发生蛋白用于颅骨缺损的安全性 成年雄性狒狒（Papio ursinus） 具体目标首先是， 确定重组人BMP的最佳剂量， 修复与天然BMP相当;第二，确定是否速率和 骨形成的程度可以通过增加剂量的 第三，确定命运和长期重塑 重组骨形态发生蛋白诱导的新骨形成。 组织学和 将使用组织形态测定法定量骨的范围 不同剂量人重组骨形成蛋白（HrBMP）诱导的再生 在不同的观察期，并通过胶原蛋白递送， 基质或多孔羟基磷灰石基质。

DESCRIPTION (adapted from the Investigator's abstract):The recently isolated and characterized bone morphogenetic proteins (BMPs) induce endochondral bone differentiation in vivo. Molecular cloning and expression of human recombinant BMPs may provide the potential for controlled initiation of bone regeneration and repair in man. While substantial progress is being made in the elucidation of the molecular and cellular mechanisms involved in BMP- induced bone differentiation, the morphogenetic potential of BMPs is predominantly based on work in rodents.The long-term objective of the proposed research is to study the efficacy and safety of native and recombinant BMPs delivered by suitable carriers in a nonhuman primate model. This work has relevance to the repair and regeneration of bone in congenital and acquired craniofacial anomalies in man. The applicant proposes to investigate the efficacy and safety of native and recombinant BMPs using nonhealing calvarial defects of adult male baboons (Papio ursinus). The specific aims are first, to determine the optimal dose of recombinant human BMP that will elicit a repair comparable to native BMPs; Second, to determine if the rate and extent of bone formation can be accelerated by increasing doses of recombinant BMP; third, to determine the fate and long term remodeling of the newly induced bone by recombinant BMP. Histology and histomorphometry will be used to quantitate the extent of bone regeneration induced by different doses of human recombinant BMP (HrBMP) at different observation periods, and delivered either by collagenous matrix or porous hydroxyapatite substrata.