Efficient in vivo bone formation by BMP-2 engineered human mesenchymal stem cells encapsulated in a projection stereolithographically fabricated hydrogel scaffold

Abstract

Background Stem cell-based bone tissue engineering shows promise for bone repair but faces some challenges, such as insufficient osteogenesis and limited architecture flexibility of the cell-delivery scaffold. Methods In this study, we first used lentiviral constructs to transduce ex vivo human bone marrow-derived stem cells with human bone morphogenetic protein-2 ( BMP-2 ) gene ( BMP -hBMSCs). We then introduced these cells into a hydrogel scaffold using an advanced visible light-based projection stereolithography (VL-PSL) technology, which is compatible with concomitant cell encapsulation and amenable to computer-aided architectural design, to fabricate scaffolds fitting local physical and structural variations in different bones and defects. Results The results showed that the BMP -hBMSCs encapsulated within the scaffolds had high viability with sustained BMP-2 gene expression and differentiated toward an osteogenic lineage without the supplement of additional BMP-2 protein. In vivo bone formation efficacy was further assessed using an intramuscular implantation model in severe combined immunodeficiency (SCID) mice. Microcomputed tomography (micro-CT) imaging indicated rapid bone formation by the BMP -hBMSC-laden constructs as early as 14 days post-implantation. Histological examination revealed a mature trabecular bone structure with considerable vascularization. Through tracking of the implanted cells, we also found that BMP -hBMSC were directly involved in the new bone formation. Conclusions The robust, self-driven osteogenic capability and computer-designed architecture of the construct developed in this study should have potential applications for customized clinical repair of large bone defects or non-unions. Electronic supplementary material The online version of this article (10.1186/s13287-019-1350-6) contains supplementary material, which is available to authorized users.

Sequential sequestrations increase the incorporation and retention of multiple growth factors in mineralized collagen scaffolds

“…Incorporating BMP2 into scaffolds for bone repair is very common and has shown to improve osteogenesis in multiple systems [36][37][38][39][40][41][42] . However, the need for doses of soluble BMP2 larger than what's normally found in the body has led to complications such as abnormal bone formation 43,44 .…”

Osteochondral Tissue Chip Derived From iPSCs: Modeling OA Pathologies and Testing Drugs

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Green Tomato Extract Prevents Bone Loss in Ovariectomized Rats, a Model of Osteoporosis

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