Mussel‐Inspired Tough Hydrogel with In Situ Nanohydroxyapatite Mineralization for Osteochondral Defect Repair

Abstract

Repairing osteochondral defects is a considerable challenge because it involves the breakdown of articular cartilage and underlying bone. Traditional hydrogels with a homogenized single‐layer structure cannot fully restore the function of osteochondral cartilage tissue. In this study, a mussel‐inspired hydrogel with a bilayer structure is developed to repair osteochondral defects. The hydrogel is synthesized by simultaneously polymerizing two layers using a one‐pot method. The resulting upper and lower gelatin methacryloyl‐polydopamine hydrogel layers are used as cartilage and subchondral bone repair layers, respectively. Polydopamine‐induced hydroxyapatite in situ mineralization takes place in the lower layer to mimic the structure of subchondral bone. The bilayer hydrogel exhibits good mechanical properties for the synergistic effect of covalent and noncovalent bonds, as well as nanoreinforcement of mineralized hydroxyapatite. To improve the tissue‐inducibility of hydrogels, transforming growth factor β3 is immobilized in the upper layer to induce cartilage regeneration, while bone morphogenetic protein 2 is immobilized in the lower layer to induce bone regeneration. Bone and cartilage repair performance of the hydrogel is examined by implantation into a full‐thickness cartilage defect of a rabbit knee joint. The bilayer‐structure hydrogel promotes regeneration of osteochondral tissue, thus providing a new option for repair of osteochondral defects.

Strategies for Using Polydopamine to Induce Biomineralization of Hydroxyapatite on Implant Materials for Bone Tissue Engineering

“…Incorporating hydrogels with biominerals can increase the generation of new bone cells in the defective sites. In this regard, Gan et al functionalized a gelatin methacryloyl hydrogel (GelMA) by the pHAF method to form a bilayer structure [ 71 ]. In this method, the upper layer consisting GelMA-PDA hydrogel served as a cartilage repair layer, whereas the lower gelatin methacrylamide-polydopamine/calcium phosphate (GelMA-PDA/HA) hydrogel worked as a subchondral bone repair layer.…”

“…To increase the efficiency of hydrogels towards tissue inducibility, transforming growth factor-beta 3 (TGF-β 3 ) was immobilized in the upper layer to stimulate cartilage regeneration. Also, BMP-2 was immobilized in the lower layer to induce bone redevelopment ( Figure 7 ) [ 71 ]. Besides improved mechanical strength, the swelling ratio (~70% reduction from GelMA hydrogels) and the stability of the GelMA-PDA/HA bilayer hydrogel were improved.…”

“…( d ) Illustration of the application of the hydrogel bilayer for the bone defect repair. Reprinted with permission from reference [ 71 ]. Copyright © 2019 WILEY-VCH.…”

A 3D, Dynamically Loaded Hydrogel Model of the Osteochondral Unit to Study Osteocyte Mechanobiology

“…While numerous studies have developed bilayer scaffolds for osteochondral defect repair models (e.g., refs. [38][39][40][41][42][43][44][45][46] ), few studies examine osteocytes in these scaffolds. A representative image of a histological section of human osteochondral tissue ( Figure 1A) illustrates articular cartilage overlaying a thin interfacial calcified cartilage layer, underlying cortical subchondral bone plate, and subchondral trabecular bone.…”

Advanced hydrogels for the repair of cartilage defects and regeneration

“…The development of OA and cartilage defects is a vicious circle: catabolic and proinflammatory mediators in the OA joints lead to the excess production of proteolytic enzymes and break down the cartilage; the defect in the cartilage in turn amplifies the inflammation in the joint [ 6 ]. As cartilage is an important tissue that serves by reducing joint friction between bones, its breakdown may contribute to the deterioration of joint function [ [7] , [8] , [9] ]. Once cartilage defects occur, the limited self-repair capability of the tissue is insufficient and no significant regeneration will occur due to the complex structure of cartilage, where no blood vessels, nerves or lymphatic tissue exists [ [10] , [11] , [12] ].…”