Biofabrication of Osteochondral Tissue Equivalents by Printing Topologically Defined, Cell-Laden Hydrogel Scaffolds

Abstract

Osteochondral defects are prone to induce osteoarthritic degenerative changes. Many tissue-engineering approaches that aim to generate osteochondral implants suffer from poor tissue formation and compromised integration. This illustrates the need for further improvement of heterogeneous tissue constructs. Engineering of these structures is expected to profit from strategies addressing the complexity of tissue organization and the simultaneous use of multiple cell types. Moreover, this enables the investigation of the effects of three-dimensional (3D) organization and architecture on tissue function. In the present study, we characterize the use of a 3D fiber deposition (3DF) technique for the fabrication of cell-laden, heterogeneous hydrogel constructs for potential use as osteochondral grafts. Changing fiber spacing or angle of fiber deposition yielded scaffolds of varying porosity and elastic modulus. We encapsulated and printed fluorescently labeled human chondrocytes and osteogenic progenitors in alginate hydrogel yielding scaffolds of 1×2 cm with different parts for both cell types. Cell viability remained high throughout the printing process, and cells remained in their compartment of the printed scaffold for the whole culture period. Moreover, distinctive tissue formation was observed, both in vitro after 3 weeks and in vivo (6 weeks subcutaneously in immunodeficient mice), at different locations within one construct. These results demonstrate the possibility of manufacturing viable centimeter-scaled structured tissues by the 3DF technique, which could potentially be used for the repair of osteochondral defects.

3D Bioprinting Using a Templated Porous Bioink

“…Accordingly, the use of alginate gels in 3D bioprinting has been limited to structurally simple objects with limited vertical size, which severely limits their application in tissue printing. [ 18 ] The emergence of hybrid multicomponent gels that integrate desirable physical properties from each constituent component represents an exciting new direction in bioink development. For instance, biodegradable polymers are commonly strengthened with osteoinductive ceramics, such as calcium phosphate, [ 19 ] nanofi brous cellulose has been used to increase the shear thinning of alginate gels, [ 20 ] while a mixture of Pluronic and acrylated Pluronic has been used to generate a synthetic gel that can be crosslinked using both temperature and ultraviolet irradiation.…”

Bioprinting of osteochondral tissues: A perspective on current gaps and future trends

“…Thus, bio printing has attracted the attention of researchers working with the quest to devise improved solutions for osteochondral healing. One of the early osteochondral tissue bioprinting efforts was attempted with EBB of two different cell types: mesenchymal stem cells with osteoinductive calcium phosphate particles, and chondrocytes on two sides of an alginate mesh scaffold [62] . After appro ximately three weeks in culture as well as in vivo experimentation, functional markers and ECM characteristics of both osteogenic and chondrogenic differentiation were observed indicating the formation of interfacial composite tissue.…”

Biofabrication: an overview of the approaches used for printing of living cells

“…Multiple-cell-type constructs were then fabricated to incorporate goat endothelial progenitor cells (EPCs) in an effort to improve the engineered bone grafts and encourage vascularisation (Fedorovich et al 2011d (Fedorovich et al 2011c). …”