Three-dimensional bioprinting biphasic multicellular living scaffold facilitates osteochondral defect regeneration

Due to tissue lineage variances and the anisotropic physiological character-istics,regenerating complex osteochondral tissues(cartilage and subchondral bone)remains a great challenge,which is primarily due to the distinct requirements for cartilage and subchondral bone regeneration.For cartilage regeneration,a significant amount of newly generated chondrocytes is required while maintaining their phenotype.Conversely,bone regeneration necessitates inducing stem cells to differentiate into osteoblasts.Additionally,the construction of the osteochondral interface is crucial.In this study,we fabricated a biphasic multicellular bioprinted scaffold mimicking natural osteochondral tissue employing three-dimensional(3D)bioprinting technol-ogy.Briefly,gelatin-methacryloyl(GelMA)loaded with articular chondrocytes and bone marrow mesenchymal stem cells(ACs/BMSCs),serving as the cartilage layer,preserved the phenotype of ACs and promoted the differentia-tion of BMSCs into chondrocytes through the interaction between ACs and BMSCs,thereby facilitating cartilage regeneration.GelMA/strontium-substituted xonotlite(Sr-CSH)loaded with BMSCs,serving as the subchondral bone layer,regulated the differentiation of BMSCs into osteoblasts and enhanced the secretion of cartilage matrix by ACs in the cartilage layer through the slow release of bioactive ions from Sr-CSH.Additionally,GelMA,serving as the matrix material,contributed to the reconstruction of the osteochondral interface.Ultimately,this biphasic multicellular bioprinted scaffold demonstrated satisfactory simultaneous regeneration of osteochondral defects.In this study,a promising strategy for the application of 3D bioprinting technology in complex tissue regeneration was proposed.

Strategies of functionalized GelMA-based bioinks for bone regeneration:Recent advances and future perspectives

Gelatin methacryloyl(GelMA)hydrogels is a widely used bioink because of its good biological properties and tunable physicochemical properties,which has been widely used in a variety of tissue engineering and tissue regeneration.However,pure GelMA is limited by the weak mechanical strength and the lack of continuous osteogenic induction environment,which is difficult to meet the needs of bone repair.Moreover,GelMA hydrogels are unable to respond to complex stimuli and therefore are unable to adapt to physiological and pathological microenvironments.This review focused on the functionalization strategies of GelMA hydrogel based bioinks for bone regeneration.The synthesis process of GelMA hydrogel was described in details,and various functional methods to meet the requirements of bone regeneration,including mechanical strength,porosity,vascularization,osteogenic differentiation,and immunoregulation for patient specific repair,etc.In addition,the response strategies of smart GelMA-based bioinks to external physical stimulation and internal pathological microenvironment stimulation,as well as the functionalization strategies of GelMA hydrogel to achieve both disease treatment and bone regeneration in the presence of various common diseases(such as inflammation,infection,tumor)are also briefly reviewed.Finally,we emphasized the current challenges and possible exploration directions of GelMA-based bioinks for bone regeneration.