Biomaterials and Tissue Engineering Laboratory, School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
School of Medical Science and Technology, Indian Institute of Technology Kharagpur, Kharagpur 721302, India.
Mater Sci Eng C Mater Biol Appl. 2020 Aug;113:110990. doi: 10.1016/j.msec.2020.110990. Epub 2020 Apr 25.
Critical bone defects arising from traumatic injury and diseases are of major health concern since they are unable to heal spontaneously without clinical intervention. In this context, bone tissue engineering provides an attractive approach to treat bone defects by providing a bioactive template which has the potential to guide osseous tissue regeneration. In this study, porous hybrid placental extracellular matrix sponge (PIMS) was fabricated by a combinatorial method using silk fibroin (SF)/placental derived extracellular matrix and subsequently evaluated its efficacy towards bone tissue regeneration. The presence of intrinsic growth factors was evidenced by immunoblotting of the extracted proteins derived from the placental derived extracellular matrix. This growth factor rich PIMS lends a unique bioactive scaffolding to human amniotic mesenchymal stem cells (HAMSCs) which supported enhanced proliferation as well as superior osteogenic differentiation. Gene expression studies demonstrated significant up-regulation of osteogenic related genes in the PIMS group. PIMS when implanted in the chick chorioallantoic membrane, significantly attracted allantoic vessels revealing its potential to stimulate angiogenesis ex vivo. Furthermore, no severe immune response to the host was observed on subcutaneous implantation of PIMS in vivo. Instead, it supported the formation of blood vessels, revealing its outstanding biocompatibility. Additionally, critical tibial defects treated with PIMS demonstrated higher bone volume after six weeks when analyzed by micro-CT, which was accompanied by high mineral density. Histological and immunofluorescence studies validated the results and revealed enhanced osseous tissue regeneration after six weeks of surgery. All these findings recapitulated that the growth factors incorporated bioactive PIMS could perform as an appropriate matrix for osteogenic differentiation and efficient bone regeneration.
创伤和疾病引起的临界骨缺损是一个主要的健康问题，因为它们在没有临床干预的情况下无法自发愈合。在这种情况下，骨组织工程通过提供具有引导骨组织再生潜力的生物活性模板，为治疗骨缺损提供了一种有吸引力的方法。在这项研究中，采用丝素蛋白 (SF)/胎盘衍生细胞外基质组合方法制备多孔混合胎盘细胞外基质海绵 (PIMS)，并随后评估其对骨组织再生的功效。从胎盘衍生细胞外基质中提取的蛋白质的免疫印迹证明了内在生长因子的存在。这种富含生长因子的 PIMS 为人类羊膜间充质干细胞 (HAMSCs) 提供了独特的生物活性支架，支持增强的增殖和优异的成骨分化。基因表达研究表明，PIMS 组中成骨相关基因的表达显著上调。当 PIMS 植入鸡胚绒毛尿囊膜时，明显吸引了尿囊血管，显示其在体外刺激血管生成的潜力。此外，在体内皮下植入 PIMS 时，未观察到宿主的严重免疫反应。相反，它支持血管的形成，显示出其出色的生物相容性。此外，用 PIMS 治疗的临界胫骨缺损在 micro-CT 分析时，在六周后显示出更高的骨体积，同时伴有更高的矿物质密度。组织学和免疫荧光研究验证了这些结果，并显示手术后六周骨组织再生增强。所有这些发现都表明，掺入生长因子的生物活性 PIMS 可以作为成骨分化和有效骨再生的合适基质。
