Osteogenesis of Human iPSC-Derived MSCs by PLLA/SF Nanofiber Scaffolds Loaded with Extracellular Matrix

Abstract

Bone defects that arise from trauma, skeletal diseases, or tumor resections have become the commonest and most thorny problems in orthopedic clinics. Recently, biocomposite materials used as artificial bone repair materials have provided a promising approach for bone regeneration. In this study, poly (l-lactide acid) (PLLA) and silk fibroin (SF) were used to fabricate nanofiber scaffolds by electrospinning technology. In order to simulate a biomimetic osteoblast microenvironment, decellularized extracellular matrix from osteoblasts was loaded into the biocomposite scaffolds (O-ECM/PLLA/SF). It was found that the O-ECM/PLLA/SF scaffolds were nontoxic for L929 cells and had good cytocompatibility. Their effects on mesenchymal stem cells derived from human-induced pluripotent stem cell (iPSC-MSC) behavior were investigated. As a result, the scaffolds with the addition of O-ECM showed enhanced alizarin red S (ARS) activity. In addition, higher expression of osteogenic gene markers such as runt-related transcription factor 2 (Runx2), collagen type I (Col-1), and osteocalcin (OCN) as well as upregulated expression of osteogenic marker protein osteopontin (OPN) and Col-1 further substantiated the applicability of O-ECM/PLLA/SF scaffolds for osteogenesis. Furthermore, the in vivo study also indicated maximal new bone formation in the skull defect model of Sprague Dawley (SD) rats treated with the O-ECM/PLLA/SF carried by human iPSC-MSCs. Hence, this study suggests that O-ECM/PLLA/SF scaffolds have a potential application in bone tissue engineering.

Chicken utricle stromal cell-derived decellularized extracellular matrix coated nanofibrous scaffolds promote auditory cell production

“…The active substances that could promote cell proliferation and differentiation were successfully preserved by decellularization, which provided a research background to promote tissue repair and regeneration for tissue engineering and organ transplantation [56]. In the previous studies, ECM can be obtained in many ways [32,57]. In this study, we improved the method for the preparation of U-dECM and the combining measures of physical and chemical methods were used to acquire U-dECM and U-dECM/PLLA/Gel scaffolds.…”

“…However, there have been no studies on the application of tissue engineering to inner ear regeneration. The decellularized extracellular matrix (ECM) contains abundant peptides, such as collagen, fibrin and proteoglycans, and the matricryptic sites exposed by these peptides can promote cell adhesion and migration [31,32]. As a kind of biomaterial derived from native tissues, ECM has been used to promote stem cell differentiation and matrix formation in many tissue-engineering applications [33,34].…”