Abstract
Osteochondral defects contain damage to both the articular cartilage and underlying subchon- dral bone, which remains a significant challenge in orthopedic surgery. Layered structure of bone, cartilage and the bone-cartilage interface must be taken into account in the case of biofabrication of the osteochondral (OC) interface. In this study, a dual layered OC interface was bioprinted using a newly developed aspiration-assisted bioprinting (AAB) technique, which has been the first time that scaffold-free bioprinting was applied to OC interface engineering. Tissue spheroids, made of human adipose-derived stem cells (ADSCs), were differentiated in three dimensions (3D) into chondrogenic and osteogenic spheroids, which were confirmed by immunostaining and histology qualitatively, and biochemistry assays and gene expression, quantitatively. Remarkably, the OC interface was bioprinted by accurate positioning of a layer of osteogenic spheroids onto a sacrificial alginate support followed by another layer of chondrogenic spheroids overlaid by the same support. Spheroids in individual zones fused and the maintenance of phenotypes in both zones confirmed the successful biofabrication of the histomorphologically-relevant OC interface. The biofabrication of OC tissue model without the use of polymeric scaffolds unveils great potential not only in regenerative medicine but also in drug testing and disease modeling for osteoarthritis.
Highlights
Osteochondral defects contain damage to both the articular cartilage and underlying subchondral bone, which remains a significant challenge in orthopedic surgery
The results demonstrated that adipose-derived stem cells (ADSCs) were able to chondrogenically differentiate in the form of spheroids and exhibit chondrogenic phenotype
Greater expression of BSP and COL1 as compared to the ADSC group was observed. These results demonstrate that chondrogenic and osteogenic induction happened in ADSC spheroids after a three-week induction of differentiation media in the 3D spheroid culture
Summary
Osteochondral defects contain damage to both the articular cartilage and underlying subchondral bone, which remains a significant challenge in orthopedic surgery. Taking the advantage of accurate positioning of tissue spheroids, this study is the first time to resemble the human OC interface using 3D scaffold-free bioprinting. This bottom-up approach with high precision renders a compact and stratified tissue arrangement, which is more biomimetic in terms of cell density and ECM organization, as compared to previously reported methods[27]. The bioprinted OC interface has the potential to be used in tissue engineering and regenerative medicine and in OA disease modeling for drug testing and the development of new therapeutic strategies
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