CRANIOFACIAL BONE REGENERATION IN PRIMATES BY BMPS

通过 BMPS 实现灵长类动物颅面骨再生

• 批准号: 2131610
• 负责人: Akepati Hari Reddi
• 金额: $ 7.26万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1993
• 资助国家: 美国
• 起止时间: 1993-09-30 至 1996-09-29
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/2131610
• 关键词: baboons; bone regeneration; collagen; congenital oral /facial /cranial defect; disease /disorder model; dosage; electrophoresis; histology; hydroxyapatites; laboratory rat; molecular cloning; normal ossification; osteogenesis; protein biosynthesis; protein purification; recombinant proteins

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.

描述（改编自研究者的摘要）：最近 分离并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 人类重组 BMP 的表达可能提供以下潜力： 控制人体骨骼再生和修复的启动。 尽管 在阐明分子机制方面正在取得实质性进展 和参与 BMP 诱导骨分化的细胞机制， BMP 的形态发生潜力主要基于以下工作： 啮齿动物。拟议研究的长期目标是研究 天然和重组 BMP 的功效和安全性 非人类灵长类动物模型中的携带者。 这项工作与 先天性和后天性颅面骨的修复和再生 人的异常现象。 申请人建议调查有效性和 使用不可愈合的颅骨缺损的天然和重组 BMP 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，以引起 修复效果与原生 BMP 相当；其次，确定速率和 骨形成的程度可以通过增加剂量来加速 重组BMP；三、定命与长远重塑 通过重组 BMP 诱导新骨的形成。 组织学和 组织形态计量学将用于定量骨的范围 不同剂量的人重组BMP（HrBMP）诱导的再生 在不同的观察时期，并通过胶原蛋白传递 基质或多孔羟基磷灰石基质。