Creating a Living Hyaline Cartilage Graft Free from Non‐Cartilaginous Constituents: An Intermediate Role of a Biomaterial Scaffold

Abstract

A novel living hyaline cartilage graft (LhCG) with controllable dimensions and free of non‐cartilaginous constituents for articular regeneration is developed. As a living graft for regenerative medicine, LhCG is purely living tissue based and truly scaffold‐free. The process of neotissue formation in LhCG is mediated by an interim biomaterial‐based novel scaffolding system. This design highlights a philosophy of using biomaterials in engineered regenerative medicine as a transient guiding facility rather than a permanent part of substitute. The fabrication is designed and practiced in a continuous and integrated process, which attributes to its simplicity in operation. Because of the intrinsic non‐cell‐adhesive property of hydrogel scaffolds, articular chondrocytes’ phenotype is always preserved throughout the whole procedure, which has been tested and approved both in vitro and in vivo. In situ grafting trials in a rabbit model showcase high success rates in both cartilage repair and graft‐host integration. Beyond cartilage repair, this LhCG model may provide a living‐tissue‐based open platform or niche for multi‐tissue regenerations.

A preclinical evaluation of an autologous living hyaline-like cartilaginous graft for articular cartilage repair: a pilot study

“…4(b-f)). As suggested before, this can be attributed to the sponge-like properties of LhCG 24 . Its lower mechanical stiffness compare to native cartilage enabled in situ remodeling and maturation, resulting in good integration with surrounding native cartilage.…”

“…Upon cell extraction and one passage (P1) of in vitro expansion, the chondrocytes were then used to construct LhCGs. The protocol for LhCG preparation has been established in our previous work 24 and is depicted in Fig. 1(b)iv-viii.…”

“…When the gel constructs were cultured at 37 °C, the gelatin microspheres rapidly dissolved and leached out of the constructs, leaving behind micro-cavities of the same size throughout the cell-laden gel phase. These resultant micro-cavitary hydrogel constructs (MCG) allow cells to proliferate vigorously and condense into isogenic groups, eventually sprouting from the gel phase into the micro-cavities (Phase Transfer Cell Culture or PTCC) 24,28 . Following prolonged culture, the micro-cavities were filled with cartilaginous neotissue aggregates formed by the outgrowing chondrocyte isogenic groups.…”

“…This results in a macro-scaled, sponge-like, synthetic scaffold-free product of LhCG, which had earlier been demonstrated to recapitulate characteristic markers of an articular cartilage in vitro. Furthermore, in a leporine model for articular cartilage repair, results strongly demonstrated the advantage of the LhCG in mediating efficacious repair in vivo 24 .…”

“…The prototype of LhCG was established previously 24 . It is constructed by culturing chondrocytes in a 3D interim scaffolding system made up of removable, non-cell adhesive micro-cavitary hydrogel (MCG) 22 .…”