Mimicking 3D bone microenvironment using a hybrid hydrogel-nanocomposite scaffold and human adipose-derived stem cells for bone differentiation and vascularization

Abstract

Bioengineered bone tissues could bypass limitations of traditional reconstructive methods such as bone grafts or foreign-body implants, but to date this approach has been limited by immaturity of engineered bones and vascularization. Pediatric human adiposederived stem cells (hADSCs) can be derived using minimally invasive procedures and are known to undergo osteogenic differentiation. Here we have taken a "design-in reverse" approach to tissue engineering by mimicking the native tissue microenvironment to bioengineer complex vascularized tissues. Specifically, we sought to optimize bone tissue engineering by modelling the bone tissue microenvironment and vascularization using hADSCs in combination with a nanocomposite biodegradable nanomaterial and hydrogel, POSS-PCL-fibrin. Our scaffolds exhibited similar architectural features to bone and Biofunct. Mater. Article 2 supported hADSC osteogenic differentiation in vitro. Extensive vascularization and formation of tissues resembling pediatric calvarial (upper part of the skull encasing the brain) bone as well as host cell infiltration yielding chimeric tissues were achieved in vivo in nude mice. Our results suggest a promising dual tissue engineering purpose for POSS-PCL-fibrin both as a scaffold for bioengineering prefabricated replacement bone tissues and potentially as a bioactive scaffold for in situ bone regeneration.