Isolation and characterization of matrix bound vesicles for bone repair

细胞外基质（ECM）衍生生物材料已用于全球超过800万例患者。然而，ECM生物材料调节细胞行为的机制尚未完全了解。最近发现的软组织ECM中的基质结合囊泡为细胞功能的调节提供了一个潜在的理论基础，类似于细胞外囊泡所观察到的。本项目将使用多学科和交叉的方法，使骨组织衍生的ECM生物材料中的基质结合囊泡的分离和表征成为可能。该项目将通过优化分离方法从骨中获得基质结合囊泡开始。然后，我们将使用OrbiSIMS、脂质组学和成像技术通过比较细胞因子、蛋白质和代谢谱来确定分离的MBV群体的病因。确定脱细胞骨MBV在细胞外小生境中的作用将使我们了解骨源性MBV的生物学影响。这反过来又可能使骨修复新疗法的潜在发展成为可能。

Extracellular matrix (ECM) derived biomaterials have been used in more than 8 million patients worldwide. Yet, the mechanisms by which ECM biomaterials modulate cell behaviour are not fully understood. Recent discovery of matrix bound vesicles in soft tissue ECM has provided a potential rationale for regulation of cell function, analogous to that observed with extracellular vesicles.This project will use multidisciplinary and cross-cutting approaches to enable the isolation and characterisation of matrix bound vesicles from bone tissue derived ECM biomaterials. The project will commence by optimising isolation methods to obtain matrix bound vesicles from bone. We will then define the aetiology of the isolated MBV population by comparison of the cytokine, protein and metabolic profiles using OrbiSIMS, lipidomics and imaging techniques. Defining the role of decellularized bone MBVs in the extracellular niche will inform our understanding of the biological impacts of bone derived MBVs. This in turn may enable the potential development of new therapeutics for bone repair.