Mussel-Inspired Tissue-Adhesive Hydrogel Based on the Polydopamine–Chondroitin Sulfate Complex for Growth-Factor-Free Cartilage Regeneration

Abstract

Glycosaminoglycan-based hydrogels are widely used for cartilage repair because glycosaminoglycans are the main component of the cartilage extracellular matrix and can maintain chondrocyte functions. However, most of the glycosaminoglycan-based hydrogels are negatively charged and cell-repellant, and they cannot host cells or favor tissue regeneration. Inspired by mussel chemistry, we designed a polydopamine-chondroitin sulfate-polyacrylamide (PDA-CS-PAM) hydrogel with tissue adhesiveness and super mechanical properties for growth-factor-free cartilage regeneration. Thanks to the abundant reactive catechol groups on the PDA, a cartilage-specific PDA-CS complex was formed by the self-assembly of PDA and CS, and then the PDA-CS complex was homogenously incorporated into an elastic hydrogel network. This catechol-group-enriched PDA-CS complex endowed the hydrogel with good cell affinity and tissue adhesiveness to facilitate cell adhesion and tissue integration. Compared with bare CS, the PDA-CS complex in the hydrogel was more effective in exerting its functions on adhered cells to upregulate chondrogenic differentiation. Because of the synergistic effects of noncovalent interactions caused by the PDA-CS complex and covalently cross-linked PAM network, the hydrogel exhibited super resilience and toughness, meeting the mechanical requirement of cartilage repair. Collectively, this tissue-adhesive and tough PDA-CS-PAM hydrogel with good cell affinity creates a growth-factor-free and biomimetic microenvironment for chondrocyte growth and cartilage regeneration and sheds light on the development of growth-factor-free biomaterials for cartilage repair.

A novel dual-adhesive and bioactive hydrogel activated by bioglass for wound healing

“…Direct addition of the CaCl 2 solution results in the rapid reaction between Ca 2+ and the guluronate blocks of alginate chains, which does not favor uniform gel formation and significantly affects the hydrogel properties. Moreover, the increased adhesiveness of BG/OSA might also be partially explained by the interlock effect, in which a rougher surface and a more viscous adhesive enable easier fluid penetration, producing more mechanical interlock joints and hence better adhesion 16,17 . All of this evidence demonstrated that BG played a multifunctional role in the BG/OSA composite hydrogel due to its unique dualadhesive property, which was not only adhesive to tissues but also to implantable materials.…”

“…The adhesive strengths of the hydrogels on the implant materials were also measured by lap-shear strength tests as reported in dry conditions 17 . Some commonly used implant materials, including silicone, titanium alloy, tricalcium phosphate (TCP), and porous TCP, were cut into strips of size 10 mm × 10 mm.…”

“…Therefore, a weak alkaline environment is of great importance for the improvement of the adhesive strength of amide linkage-based adhesive hydrogels to tissues. The adhesion strength of the hydrogels to materials may be affected by some factors 5,15,16 , and an improvement in the viscosity of the hydrogels may result in stronger adhesion to the materials 17 .…”

Effect of matrix stiffness and adhesion ligand density on chondrogenic differentiation of mesenchymal stem cells

“…Increasing evidence has focused on the control of material properties of these systems by changing the chemical components, which simultaneously varied ECM adhesive ability or mechanics, making them become possible to regulate cell behavior and meet the requirement of cartilage repair (Benmassaoud, Gultian, DiCerbo, & Vega, 2019). Compared with bare chondroitin sulfate (CS), mussel-inspired tissue adhesive hydrogel based on polydopamine-CS complex was more effective in exerting its functions on adhered cells to upregulate chondrogenic differentiation (Han et al, 2018). Besides, polymeric scaffolds modified with arginine-glycine-aspartic acid (RGD) adhesion ligands have been used to enhance cell-matrix interaction and influence the differentiation of stem cells (Lee, Kim, & Lee, 2016).…”

Factors That Determine the Adhesive Strength in a Bioinspired Bone Tissue Adhesive

“…Aside from non-degradable adhesives [1], most biocompatible and biodegradable tissue adhesives utilize crosslinking mechanisms inspired by natural (marine) adhesives. The most common approach to creating adhesion is to incorporate a modified amino acid, L-DOPA (e.g., as a pendant group, onto a polymer) [2,3]. Coacervation and nanoscale electrostatic interactions are also sufficient to create relatively strong tissue adhesion [4][5][6][7].…”