Abstract
Acellular soft hydrogels are not ideal for hard tissue engineering given their poor mechanical stability, however, in combination with cellular components offer significant promise for tissue regeneration. Indeed, nanocomposite bioinks provide an attractive platform to deliver human bone marrow stromal cells (HBMSCs) in three dimensions producing cell-laden constructs that aim to facilitate bone repair and functionality. Here we present the in vitro, ex vivo and in vivo investigation of bioprinted HBMSCs encapsulated in a nanoclay-based bioink to produce viable and functional three-dimensional constructs. HBMSC-laden constructs remained viable over 21 d in vitro and immediately functional when conditioned with osteogenic media. 3D scaffolds seeded with human umbilical vein endothelial cells (HUVECs) and loaded with vascular endothelial growth factor (VEGF) implanted ex vivo into a chick chorioallantoic membrane (CAM) model showed integration and vascularisation after 7 d of incubation. In a pre-clinical in vivo application of a nanoclay-based bioink to regenerate skeletal tissue, we demonstrated bone morphogenetic protein-2 (BMP-2) absorbed scaffolds produced extensive mineralisation after 4 weeks (p < 0.0001) compared to the drug-free and alginate controls. In addition, HBMSC-laden 3D printed scaffolds were found to significantly (p < 0.0001) support bone tissue formation in vivo compared to acellular and cast scaffolds. These studies illustrate the potential of nanoclay-based bioink, to produce viable and functional constructs for clinically relevant skeletal tissue regeneration.
Highlights
Skeletal regeneration using innovative tissue engineering approaches has received considerable attention in recent years
Hydrogel-like biomaterials can actively facilitate this process with the inclusion of a drug delivery system or living stem/progenitor cells (e.g. human bone marrow stromal cells (HBMSCs) [9])
Acellular scaffolds alone appear insufficient/limited in their ability to aid the complete regeneration of functional bone tissue, a new generation of bioinks are needed to: i) allow the inclusion of HBMSCs within the implantable construct, ii) enable sustained drug delivery and, iii) promote skeletal differentiation
Summary
Skeletal regeneration using innovative tissue engineering approaches has received considerable attention in recent years. Generate functional constructs within a short period of time after printing and, iii) stimulate the host microenvironment to aid tissue ingrowth and tissue infiltration and integration. Acellular 3D bioprinting strategies are typically attractive, relying on the intrinsic functional properties of the printed material to attract host cells to aid tissue integration [3]. Hydrogel-like biomaterials can actively facilitate this process with the inclusion of a drug delivery system (e.g. plasmid DNA [8]) or living stem/progenitor cells (e.g. HBMSCs [9]). Acellular scaffolds alone appear insufficient/limited in their ability to aid the complete regeneration of functional bone tissue, a new generation of bioinks are needed to: i) allow the inclusion of HBMSCs within the implantable construct, ii) enable sustained drug delivery and, iii) promote skeletal differentiation [10]
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