Biofabrication of Tissue-Engineered Cartilage Constructs Through Faraday Wave Bioassembly of Cell-Laden Gelatin Microcarriers

Acoustic biofabrication is an emerging strategy in tissue engineering due to its mild and fast manufacturing process. Herein, tissue-engineered cartilage constructs with high cell viability are fabricated from cell-laden gelatin microcarriers (GMs) through Faraday wave bioassembly, a typical acoustic "bottom-up" manufacturing process. Assembly modules are first prepared by incorporating cartilage precursor cells, the chondrogenic cell line ATDC5, or bone marrow-derived mesenchymal stem cells (BMSCs), into GMs. Patterned structures are formed by Faraday wave bioassembly of the cell-laden GMs. Due to the gentle and efficient assembly process and the protective effects of microcarriers, cells in the patterned structures maintain high activity. Subsequently, tissue-engineered cartilage constructs are obtained by inducing cell differentiation of the patterned structures. Comprehensive evaluations are conducted to verify chondrocyte differentiation and the formation of cartilage tissue constructs in terms of cell viability, morphological analysis, gene expression, and matrix production. Finally, implantation studies with a rat cartilage defect model demonstrate that these tissue-engineered cartilage constructs are beneficial for the repair of articular cartilage damage in vivo. This study provides the first biofabrication of cartilage tissue constructs using Faraday wave bioassembly, extending its application to engineering tissues with a low cell density. Cell-laden gelatin microcarriers are employed as modules to fabricate patterned structures by Faraday wave bioassembly. After inducing cell differentiation, tissue-engineered cartilage constructs are obtained and can effectively promote the repair of cartilage defects. This study broadens the application of Faraday wave bioassembly to the construction of cartilage tissue, opening the door for engineering tissues with a low cell density. image