Utilization of an Acellular Cartilage Matrix‐Based Photocrosslinking Hydrogel for Tracheal Cartilage Regeneration and Circumferential Tracheal Repair

Abstract Acellular cartilage matrix (ACM)‐based hydrogels hold promise for use in the context of tracheal cartilage regeneration owing to the ease with which they can be molded into specific shapes and their intrinsic cartilage‐specific microenvironmental properties. In this report, an acrylic anhydride‐modified ACM (Ac‐matrix) hydrogel is fabricated for utilization in the context of tracheal cartilage regeneration and circumferential tracheal repair. Hydrogels are successfully prepared with a range of Ac‐matrix concentrations (4%, 6%, and 8%) and found that mechanical strength increases with rising Ac‐matrix concentrations whereas swelling and degradation ratio values decline. These Ac‐matrix hydrogels exhibit satisfactory cytocompatibility when loaded with chondrocytes. Chondrocyte‐loaded 6% hydrogels are able to support cartilage formation both in vitro and in vivo across a range of chondrocyte densities (5, 10, 20, and 40 million chondrocytes per mL), with increasing density being conducive to more homogenous cartilage formation. A homogeneously tubular tracheal cartilage construct is additionally generated and supports circumferential tracheal reconstruction in a rabbit tracheal lesion model system, with a biological structure and function consistent with those of the native trachea. These results suggest that this Ac‐matrix hydrogel platform is well‐suited to use in the context of tracheal cartilage regeneration, thus offering the potential to support circumferential tracheal reconstruction.