Cell-Derived Matrix Enhances Osteogenic Properties of Hydroxyapatite

Abstract

The study aimed to evaluate osteogenic properties of hydroxyapatite (HA) scaffold combined with extracellular matrix (ECM) derived in vitro from rat primary calvarial osteoblasts or dermal fibroblasts. The cellular viability, and the ECM deposited onto synthetic HA microparticles were assessed by MTT, Glycosaminoglycan, and Hydroxyproline assays as well as immunohistochemistry and scanning electron microscopy after 21 days of culture. The decellularized HA-ECM constructs were implanted in critical-sized calvarial defects of Sprague-Dawley rats, followed by bone repair and local inflammatory response assessments by histomorphometry and immunohistochemistry at 12 weeks postoperatively. We demonstrated that HA supported cellular adhesion, growth, and ECM production in vitro, and the HA-ECM constructs significantly enhanced calvarial bone repair (p<0.05, Mann-Whitney U-test), compared with HA alone, despite the significantly increased number of CD68+ macrophages, and foreign body giant cells (p<0.05, Mann-Whitney U-test). Selective accumulation of bone sialoprotein, osteopontin, and periostin was observed at the tissue-HA interfaces. In conclusion, in vitro-derived ECM mimics the native bone matrix, enhances the osteogenic properties of the HA microparticles, and might modulate the local inflammatory response in a bone repair-favorable way. Our findings highlight the ability to produce functional HA-ECM constructs for bone tissue engineering applications.

Bone Regeneration Potential of Stem Cells Derived from Periodontal Ligament or Gingival Tissue Sources Encapsulated in RGD-Modified Alginate Scaffold

“…17,18 However, in the current study, stem cells were not cultured in osteogenic media prior to surgical transplantation; yet, encapsulated PDLSCs and GMSCs promoted bone regeneration in situ without any premineralization. Additionally, we confirmed that the presence of RGD tripeptide and the small diameter of alginate microspheres are crucial factors for MSC survival and fate determination.…”

“…15,16 Studies have confirmed that providing a suitable microenvironment for MSC proliferation and differentiation in response to exogenous stimuli and growth factors is a critical step toward clinical applications. [17][18][19][20][21][22][23] Several types of scaffolds have been used to support growth and differentiation of progenitor cells for bone regeneration, including natural polymers (e.g., alginates). 23,24 Alginates are natural heteropolysaccharides that are isolated from brown sea algae.…”

Engineered decellularized matrices to instruct bone regeneration processes

“…In vivo, eECM displayed efficient engraftment [74] and vascularization [75] and was capable to undergo remodeling onto an immature osteoid tissue [71]. eECM was successfully shown to act as functional/instructive template for the regulation and/or recruitment of osteoprogenitor cells, although it could not ectopically induce frank bone formation in mouse and rat models [71,76].…”

Dental and orofacial mesenchymal stem cells in craniofacial regeneration: The prosthodontist’s point of view

“…Such interactions between stem cells and biomaterials have largely been studied by introducing the cells into 2- or 3-dimensional scaffolds, or by encapsulating the cells within hydrogel biomaterials. 30–32 Alginate hydrogel has been used extensively as a vehicle for stem cell delivery in tissue regeneration. 31,32 The ability to control the spatial presentation of alginate enables the examination of the effects of alginate hydrogel on stem cell differentiation in a systematic way.…”