A Natural Hydrogel with Prohealing Properties Enhances Tendon Regeneration

Abstract

Tendon regeneration and reduction of peritendinous adhesion remain major clinical challenges. This study addresses these challenges by adopting a unique hydrogel derived from the skin secretion of Andrias davidianus (SSAD) and taking advantage of its biological effects, adhesiveness, and controllable microstructures. The SSAD‐derived hydrogel contains many cytokines, which could promote tendon healing. In vitro, leach liquid of SSAD powder could promote tendon stem/progenitor cells migration. In vivo, the SSAD‐derived hydrogel featuring double layers possesses strong adhesiveness and could reconnect ruptured Achilles tendons of Sprague‐Dawley rats without suturing. The intimal SSAD‐derived hydrogel, with a pore size of 241.7 ± 21.0 µm, forms the first layer of the hydrogel to promote tendon healing, and the outer layer SSAD‐derived hydrogel, with a pore size of 3.3 ± 1.4 µm, reducing peritendinous adhesion by serving as a dense barrier. Additionally, the SSAD‐derived hydrogel exhibits antioxidant and antibacterial characteristics, which further contribute to the reduction of peritendinous adhesion. In vivo studies suggest that the SSAD‐derived hydrogel reduces peritendinous adhesion, increases collagen fiber deposition, promotes cell proliferation, and improves the biomechanical properties of the regenerated tendons, indicating better functional restoration. The SSAD‐derived bilayer hydrogel may be a feasible biomaterial for tendon repair in the future.

Recent advances in adhesive materials used in the biomedical field: adhesive properties, mechanism, and applications

“…78 However, its strong hydrophilicity makes the structure unstable, so it is often necessary to cross-link modified gelatin for use under physiological conditions. 79…”

Applications of functionally-adapted hydrogels in tendon repair

“…As hydrogels composed of natural materials, SSAD-derived hydrogels contained extensive amino acids and cytokines that promote tendon healing, and even show exceptional antioxidant and antibacterial abilities. These hydrogels were therefore expected to serve as a scaffold which could both promote tendon healing and prevent peritendinous adhesion ( Dang et al, 2022 ). In another study, Cai et al developed a self-healing hyaluronic acid (HA) hydrogel which encircled the repaired tendons to prevent the formation of peritendinous adhesions.…”

“…The released growth factors could bring benefits to tendon healing by promoting the migration and proliferation of TDSCs. In vivo experiments indicated that the hydrogel gave rise to functional tendon repair by triggering collagen deposition, cell proliferation and inhibiting peritendinous adhesion ( Dang et al, 2022 ). Compared to a single growth factor, it has been purposed that the combination of multiple growth factors would be superior in imitating the complicated in vivo environment ( Molloy et al, 2003 ; Indrawattana et al, 2004 ; Gaspar et al, 2015 ).…”

Functional biomaterials for tendon/ligament repair and regeneration

“…Dang et al . [ 140 ] developed a unique hydrogel using Skin Secretions of Andrias Davidianus (SSAD), which is biologically active, adhesive and possesses controllable microstructures. SSAD-derived hydrogel with double layers demonstrated strong adhesiveness in vivo and could repair ruptured Achilles tendons in rats without suturing.…”