Department of Biomedical Engineering, Charles V. Schaefer School of Engineering and Sciences, Stevens Institute of Technology, Hoboken, New Jersey07030, United States.
ACS Appl Bio Mater. 2022 Dec 19;5(12):5634-5644. doi: 10.1021/acsabm.2c00686. Epub 2022 Nov 14.
With the emphasis on collagen and hydroxyapatite, the main structural components of bone tissue, synthetic grafts fall short of matching the clinical efficacy of autologous bone grafts. Excluded non-collagenous protein (NCPs) and carbohydrates also participate in critical cell signaling cascades and guide mineral deposition during intermediate stages of bone healing. By mimicking the native fracture repair process, polymeric scaffolds that incorporate calcium-binding moieties present in fibrocartilage can potentially enhance their bioactivity, mineralization, and bone growth. Likewise, coating polymeric fibers with serum albumin is an additional strategy that can impart collagen-like biofunctionality and further increase mineral deposition on the fibrous surface. Here, a combination of electrospun polycaprolactone (PCL) fibers with chondrocyte-derived decellularized extracellular matrix (dECM) and albumin coating were investigated as a fibrocartilage-mimetic scaffold that can serve as a woven bone precursor for bone regeneration. PCL fibrous constructs coated with dECM and albumin are shown to synergistically increase calcium concentration and calcium phosphate (CaP) deposition in a simulated body fluid biomineralization assay. Albumin/dECM coating increased osteoblast proliferation and mineral deposition in culture. In contrast, CaP coating transformed osteoblast bone lining morphology into cuboidal phenotype and arrested their proliferation. Cell sheets of osteoblasts cultured on dECM/albumin/CaP-coated constructs exhibited an increase in calcium deposition and secretion of collagen, osteopontin, osteocalcin, and bone morphogenetic protein. These results highlight the potential of biomolecular coatings to enhance bone-mimetic properties of synthetic nanofibrous scaffolds, stimulate critical protein and mineral deposition, and augment the bone's capacity to heal. Thus, mimicking the intermediate stages of bone regeneration by incorporating calcium-binding moieties may prove to be a useful strategy for improving the clinical outcomes of synthetic bone grafts.
重点关注胶原蛋白和羟磷灰石，这是骨组织的主要结构成分，合成移植物在匹配自体骨移植物的临床效果方面存在不足。排除非胶原蛋白 (NCPs) 和碳水化合物也参与关键的细胞信号级联反应，并在骨愈合的中间阶段指导矿物质沉积。通过模拟天然骨折修复过程，掺入纤维软骨中存在的钙结合部分的聚合物支架有可能增强其生物活性、矿化和骨生长。同样，在聚合物纤维上涂覆血清白蛋白也是一种额外的策略，可以赋予胶原样生物功能性，并进一步增加纤维表面的矿物质沉积。在这里，研究了一种组合，即带有软骨细胞衍生去细胞外基质 (dECM) 和白蛋白涂层的电纺聚己内酯 (PCL) 纤维，作为一种纤维软骨模拟支架，可作为编织骨前体用于骨再生。结果表明，用 dECM 和白蛋白涂层的 PCL 纤维协同增加了在模拟体液生物矿化测定中的钙离子浓度和磷酸钙 (CaP) 沉积。白蛋白/dECM 涂层增加了培养物中成骨细胞的增殖和矿物质沉积。相比之下，CaP 涂层将成骨细胞的骨衬里形态转变为立方形表型并阻止其增殖。在 dECM/白蛋白/CaP 涂层构建体上培养的成骨细胞片层显示出钙沉积和胶原蛋白、骨桥蛋白、骨钙素和骨形态发生蛋白分泌的增加。这些结果强调了生物分子涂层增强合成纳米纤维支架的骨模拟特性、刺激关键蛋白质和矿物质沉积以及增强骨愈合能力的潜力。因此，通过掺入钙结合部分模拟骨再生的中间阶段可能被证明是改善合成骨移植物临床效果的有用策略。
