In Vivo Osteogenic Differentiation of Human Dental Pulp Stem Cells Embedded in an Injectable In Vivo‐Forming Hydrogel

Abstract

In this study, human dental pulp stem cells (hDPSCs) are examined as a cellular source for bone tissue engineering using an in vivo-forming hydrogel. The hDPSCs are easily harvested in large quantities from extracted teeth. The stemness of harvested hDPSCs indicates their relative tolerance to ex vivo manipulation in culture. The in vitro osteogenic differentiation of hDPSCs is characterized using Alizarin Red S (ARS), von Kossa (VK), and alkaline phosphatase (ALP) staining. The solution of hDPSCs and a methoxy polyethylene glycol-polycaprolactone block copolymer (PC) is easily prepared by simple mixing at room temperature and in no more than 10 s it forms in vivo hydrogels after subcutaneous injection into rats. In vivo osteogenic differentiation of hDPSCs in the in vivo-forming hydrogel is confirmed by micro-computed tomography (CT), histological staining, and gene expression. Micro-CT analysis shows evidence of significant tissue-engineered bone formation in hDPSCs-loaded hydrogel in the presence of osteogenic factors. Differentiated osteoblasts in in vivo-forming hydrogel are identified by ARS and VK staining and are found to exhibit characteristic expression of genes like osteonectin, osteopontin, and osteocalcin. In conclusion, hDPSCs embedded in an in vivo-forming hydrogel may provide benefits as a noninvasive formulation for bone tissue engineering applications.

Injectable hydrogels for cartilage and bone tissue engineering

“…In recent years, synthetic biomaterials-based injectable hydrogels for bone tissue engineering have attracted attention. Jang et al 277 have investigated an injectable in vivo forming hydrogel scaffold made of methoxy polyethylene glycol-b-polycaprolactone block copolymer for bone tissue engineering. Differentiated osteoblasts encapsulated in the hydrogel exhibit characteristic expression of osteonectin, osteopontin, and osteocalcin.…”

Nanomaterials for Tissue Engineering In Dentistry

“…In vivo forming hydrogel can be prepared as a solution which gels, it can incorporate stem cells and signaling molecules simply by mixing, it can also reach the site through injection by syringe in vivo. They can be prepared by various biomaterials classified as natural, such as collagen, fibrin, alginate, heparin, hyaluronic acid, chitosan, agarose, etc., and/ or synthetics, such as polyethylene glycol (PEG), in association with synthetic polyesters like PLA, PGA, PLGA, PCL, or poloxamers [105,106,107,108]. …”

BMP2-modified injectable hydrogel for osteogenic differentiation of human periodontal ligament stem cells

“…Recently, we reported a methoxy polyethylene glycol-polycaprolactone block copolymer (MPEG-PCL [MC]) as an injectable in situ -forming hydrogel for the delivery of several biologic factors 35–39 . Because aqueous solutions of MC exhibited the solution to gelation transition at body temperatures, subcutaneous injection of an MC solution into an animal resulted in the rapid formation of a hydrogel depot.…”