CST6-mRNA activated matrices for efficient bone regeneration

项目摘要 骨再生是一个精心安排的动态过程，涉及几个关键因素 生物参与者，包括生长因子和细胞。骨组织工程的目标是 提供一个促进和增强自然骨再生的环境 进程。CST6是一种半胱氨酸蛋白酶抑制剂，在多种组织中高度表达 骨髓瘤患者的样本没有任何骨溶解损害，与那些有 至少有一处溶骨性病变。体外初步研究表明，CST6(在重组的 蛋白质形式)促进成骨细胞分化，抑制破骨细胞分化。 CmRNA具有完全在细胞质中发挥作用的独特优势(避免了 需要核进入)，从而导致期望的靶向瞬时表达 具有巨大潜力的蛋白质，可以克服蛋白质和 基于DNA的方法。具体地说，本研究旨在开发一种基于生物材料的 释放cmRNA(CST6)以诱导体内骨再生的递送系统。我们的 目的：1)证明纳米颗粒负载的cmR NA(CST6)可以有效地 触发成骨分化并抑制破骨细胞成熟；2)评估骨骼 携带CST6基因的单侧胶原支架的再生效果 大鼠股骨干缺损的实验研究

Project Summary Bone regeneration is a carefully orchestrated dynamic process that involves several key biological players, including growth factors and cells. Bone tissue engineering aims to provide an environment that facilitates and augments the natural bone regeneration process. CST6 is a cysteine protease inhibitor that is highly expressed in multiple myeloma patient samples lacking any bone lytic lesion, compared to those samples with at least one bone lytic lesion. In vitro pilot studies show that CST6 (in the recombinant protein form) promotes osteoblast differentiation and inhibit osteoclast differentiation. CmRNA has the unique advantage of functioning entirely in the cytoplasm (avoiding the need for nuclear entry) thereby, leading to a targeted transient expression of desired proteins with immense potential to overcome the challenges that exist with protein and DNA based approaches. Specifically, this study aims to develop a biomaterial-based delivery system that releases cmRNA (CST6) to induce in vivo bone regeneration. Our aims are 1) to demonstrate that nanoparticle loaded cmRNA (CST6) can efficiently trigger osteogenic differentiation and inhibit osteoclast maturation and 2) to assess bone regeneration efficacy of a collagen scaffold that delivers cmRNA (CST6) in unilateral diaphyseal femoral defects in rats