Osteochondral tissue engineering has shown an increasing development to provide suitable strategies for the regeneration of damaged cartilage and underlying subchondral bone tissue. For reasons of the limitation in the capacity of articular cartilage to self-repair, it is essential to develop approaches based on suitable scaffolds made of appropriate engineered biomaterials. The combination of biodegradable polymers and bioactive ceramics in a variety of composite structures is promising in this area, whereby the fabrication methods, associated cells and signalling factors determine the success of the strategies. The objective of this review is to present and discuss approaches being proposed in osteochondral tissue engineering, which are focused on the application of various materials forming bilayered composite scaffolds, including polymers and ceramics, discussing the variety of scaffold designs and fabrication methods being developed. Additionally, cell sources and biological protein incorporation methods are discussed, addressing their interaction with scaffolds and highlighting the potential for creating a new generation of bilayered composite scaffolds that can mimic the native interfacial tissue properties, and are able to adapt to the biological environment.
Poor vascularization is the key limitation for long-term acceptance of large three-dimensional (3D) tissue engineering constructs in regenerative medicine. 45S5 Bioglass Ò was investigated given its potential for applications in bone engineering. Since native Bioglass Ò shows insufficient angiogenic properties, we used a collagen coating, to seed human adipose tissue-derived stem cells (hASC) confluently onto 3D 45S5 Bioglass Ò -based scaffolds. To investigate vascularization by semiquantitative analyses, these biofunctionalized scaffolds were then subjected to in vitro human umbilical vein endothelial cells formation assays, and were also investigated in the chorioallantoic membrane (CAM) angiogenesis model, an in vivo angiogenesis assay, which uses the CAM of the hen's egg. In their native, nonbiofunctionalized state, neither Bioglass Ò -based nor biologically inert fibrous polypropylene control scaffolds showed angiogenic properties. However, significant vascularization was induced by hASC-seeded scaffolds (Bioglass Ò and polypropylene) in the CAM angiogenesis assay. Biofunctionalized scaffolds also showed enhanced tube lengths, compared to unmodified scaffolds or constructs seeded with fibroblasts. In case of biologically inert hernia meshes, the quantification of vascular endothelial growth factor secretion as the key angiogenic stimulus strongly correlated to the tube lengths and vessel numbers in all models. This correlation proved the CAM angiogenesis assay to be a suitable semiquantitative tool to characterize angiogenic effects of larger 3D implants. In addition, our results suggest that combinations of suitable scaffold materials, such as 45S5 Bioglass Ò , with hASC could be a promising approach for future tissue engineering applications.
Multilayered scaffolds that provide tailored space-specific biological and mechanical functions are promising for interface tissue engineering such as in osteochondral tissue regeneration. In this study, fabrication techniques, including foam replication, gelation, and freeze-drying techniques, were combined in order to manufacture stratified scaffolds mimicking the layered structure of native osteochondral tissue. 45S5 Bioglass ® and alginate were used to fabricate 3D highly porous (composite) scaffolds for the underlying subchondral bone layer. Freeze-dried alginate-based scaffolds were produced for the cartilage layer. Finally, both layers were integrated using a novel alginate/45S5 Bioglass ® hybrid interface acting as an adhesive, which functions as the cartilage-bone interfacial layer. Novel multilayered scaffolds were optimized to achieve the complex requirements for osteochondral tissue engineering such as the 3D architecture, porous structure, physical, and mechanical properties, which are presented and discussed in the context of the intended application of the novel scaffolds in osteochondral tissue regeneration.
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