Bioprinting and regeneration of auricular cartilage using a bioactive bioink based on microporous photocrosslinkable acellular cartilage matrix

Tissue engineering provides a promising strategy for auricular reconstruction.Although the first international clinical breakthrough of tissue-engineered auricular reconstruction has been realized based on polymer scaffolds,this approach has not been recognized as a clinically available treatment because of its unsatisfactory clinical efficacy.This is mainly since reconstruction constructs easily cause inflammation and deformation.In this study,we present a novel strategy for the development of biological auricle equivalents with precise shapes,low immunogenicity,and excellent mechanics using auricular chondrocytes and a bioactive bioink based on biomimetic microporous methacrylate-modified acellular cartilage matrix(ACMMA)with the assistance of gelatin methacrylate(GelMA),poly(ethylene oxide)(PEO),and polycaprolactone(PCL)by integrating multi-nozzle bioprinting technology.Photocrosslinkable ACMMA is used to emulate the intricacy of the cartilage-specific microenvironment for active cellular behavior,while GelMA,PEO,and PCL are used to balance printability and physical properties for precise structural stability,form the microporous structure for unhindered nutrient exchange,and provide mechanical support for higher shape fidelity,respectively.Finally,mature auricular cartilage-like tissues with high morphological fidelity,excellent elasticity,abundant cartilage lacunae,and cartilage-specific ECM deposition are successfully regenerated in vivo,which provides new opportunities and novel strategies for the fabrication and regeneration of patient-specific auricular cartilage.

3D porous acellular cartilage matrix scaffold with surface mediated sustainable release of TGF-β3 for cartilage engineering

Acellular tissue matrix scaffolds are much closer to tissue’s complex natural structure and biological characteristics,thus assess great advantages in cartilage engineering.We used rabbit costal cartilage to prepare acellular microfilaments and further 3D porous acellular cartilage scaffold via crosslinking.Poly(_L-lysine)/hyaluronic acid(PLL/HA)multilayer film was then built up onto the surface of the resulting porous scaffold.Furthermore,TGF-β3 was loaded into the PLL/HA multilayer film coated scaffold to obtain a 3D porous acellular cartilage scaffold with sustained releasing of TGF-β3 up to 60 days.The success of this project will provide a new way for the treatment of articular cartilage defects.Meanwhile,the anchoring and on-site sustained releasing of growth factors mediated by polyelectrolyte multilayered film can also provide a new method for improving the biocompatibility and the biofunctionality for other implanted biomaterials.