Cartilage Lacuna‐Inspired Microcarriers Drive Hyaline Neocartilage Regeneration

Abstract

Cartilage equivalents from hydrogels containing chondrocytes exhibit excellent potential in hyaline cartilage regeneration, yet current approaches have limited success at reconstituting the architecture to culture nondifferentiated chondrocytes in vitro. In this study, specially designed lacunar hyaluronic acid microcarriers (LHAMCs) with mechanotransductive conditions that rapidly form stable hyaluronic acid (HA) N‐hydroxy succinimide ester (NHS‐ester) are reported. Specifically, carboxyl‐functionalized HA is linked to collagen type I via amide‐crosslinking, and gas foaming produced by ammonium bicarbonate forms concave surface of the microcarriers. The temporal 3D culture of chondrocytes on LHAMCs uniquely remodels the extracellular matrix to induce hyaline cartilaginous microtissue regeneration and prevents an anaerobic‐to‐aerobic metabolism transition in response to the geometric constraints. Furthermore, by inhibiting the canonical Wnt pathway, LHAMCs prevent β‐catenin translocation to the nucleus, repressing chondrocyte dedifferentiation. Additionally, the subcutaneous implantation model indicates that LHAMCs display favorable cytocompatibility and drive robust hyaline chondrocyte‐derived neocartilage formation. These findings reveal a novel strategy for regulating chondrocyte dedifferentiation. The current study paves the way for a better understanding of geometrical insight clues into mechanotransduction interaction in regulating cell fate, opening new avenues for advancing tissue engineering.

Microphysiological Constructs and Systems: Biofabrication Tactics, Biomimetic Evaluation Approaches, and Biomedical Applications

“…[144,145] A study developed microcarriers suitable for chondrocyte growth for in vitro expansion and regenerative medicine applications (Figure 5E). [146] A bone-on-a-chip with a sensor replicates the osteogenesis (Figure 5F). [147] 2.1.9.…”

“…Reproduced with permission. [146] Copyright 2023, Wiley-VCH. F) Bone-on-a-chip integrated biosensors.…”

“…E) Concave microenvironment for the chondrocyte formed by LHAMC microcarrier. Reproduced with permission [146]. Copyright 2023, Wiley-VCH.…”

Advances Focusing on the Application of Decellularized Extracellular Matrix in Periodontal Regeneration

“…Therefore, functional groups are crosslinked by physical and chemical methods and will make a revolution in the future fabrication and application of dECM by improving the mechanical properties of dECMs and promoting the repair of damaged tissues. Meanwhile, since dECM materials are abundant in certain functional groups such as hydroxyl, acyl, peptide bonds, and hydrogen bonds, they promote drug loading through crosslinking reactions such as amide crosslinking [ 104 ] and crosslinks via the interaction of aldehyde groups with amine groups of lysine or hydroxylysine [ 45 ]. During the past twenty years, scientists have attempted to modify dECM material to improve the biomechanical performance and maximize the translational potential of dECM.…”

Metabolic regulation by biomaterials in osteoblast

“…Chondrocytes cultured on LHAMC undergo unique remodeling of the extracellular matrix, inducing hyaline cartilage regeneration and preventing metabolic transition. LHAMC also inhibit the Wnt pathway, preventing chondrocyte dedifferentiation ( Ding et al, 2023 ).…”