A versatile pH sensitive chondroitin sulfate–PEG tissue adhesive and hydrogel

Abstract

We developed a chondroitin sulfate - polyethylene glycol (CS-PEG) adhesive hydrogel with numerous potential biomedical applications. The carboxyl groups on chondroitin sulfate (CS) chains were functionalized with N-hydroxysuccinimide (NHS) to yield chondroitin sulfate succinimidyl succinate (CS-NHS). Following purification, the CS-NHS molecule can react with primary amines to form amide bonds. Hence, using six arm polyethylene glycol amine PEG-(NH2)6 as a crosslinker we formed a hydrogel which was covalently bound to proteins in tissue via amide bonds. By varying the initial pH of the precursor solutions, the hydrogel stiffness, swelling properties, and kinetics of gelation could be controlled. The sealing/adhesive strength could also be modified by varying the damping and storage modulus properties of the material. The adhesive strength of the material with cartilage tissue was shown to be ten times higher than that of fibrin glue. Cells encapsulated or in direct contact with the material remained viable and metabolically active. Furthermore, CS-PEG material produced minimal inflammatory response when implanted subcutaneously in a rat model and enzymatic degradation was demonstrated in vitro. This work establishes an adhesive hydrogel derived from biological and synthetic components with potential application in wound healing and regenerative medicine.

Hydrogels for the Repair of Articular Cartilage Defects

“…Hydrogels encapsulating chondrocytes were attached to cartilage explants and implanted subcutaneously in athymic mice for 5 weeks; cells remained viable and the hydrogels remained firmly attached to the cartilage. 150 Adhesion to articular cartilage was 10 times stronger than that of fibrin glue, 247 and mechanical evaluation indicated that the hydrogel failed before the interface did. 150 These hydrogels are currently being investigated in phase II trials (ChonDux; Cartilix).…”

“…150,247 The polysaccharide was modified with methacrylate groups to bind to photopolymerizable PEG hydrogels and with aldehyde groups to react with amines in surrounding tissue via a Schiff-base reaction. Hydrogels encapsulating chondrocytes were attached to cartilage explants and implanted subcutaneously in athymic mice for 5 weeks; cells remained viable and the hydrogels remained firmly attached to the cartilage.…”

Physicochemical Characteristics of Gradual Fractionation Ingredients of Industrial Galactomannan Gums from Gleditsia microphylla and Cyamopsis tetragonoloba

“…For example, double-network hydrogels (DN hydrogels)-two cross-linked networks with strong asymmetric structures-have demonstrated enhanced and balanced mechanical properties between strength and toughness by the tuning of interintramolecular interactions and structures within and between two networks (Gong and Osada 2010;Gong 2010). Due to the good biocompatibility, flexibility in fabrication, variable composition, and desirable physical characteristics of the two kinds of gums mentioned above, their hydrogels alone or combined with cells could be used in biomedical applications (Slaughter et al 2009;Strehin et al 2010). Nevertheless, some materials lack adequate mechanical properties, tunable structure, and degradability, which can lead to potential immunogenic responses that compromise their utilization as biomaterials (Zhu 2010).…”

Bonding and Fusion of Meniscus Fibrocartilage Using a Novel Chondroitin Sulfate Bone Marrow Tissue Adhesive

“…33,34 For the meniscus application, we require a material that binds to meniscus and supports MFC viability and migration, and prefer a material that promotes cell proliferation and ECM production. MFCs were able to survive, proliferate, and produce meniscus ECM when encapsulated in various CS-BM formulations, whereas they were not viable when encapsulated in CS-PEG (Fig.…”

“…We have developed an innovative, chemically modified chondroitin sulfate (CS) tissue adhesive suitable for use in orthopedic applications. 33,34 CS is an appealing material due to its ability to promote new cartilage development by musculoskeletal progenitor cells. 35 Previously, we combined the adhesive technology with IOB to form hydrogels capable of binding soft tissues with mechanical strength exceeding that of fibrin glue and of supporting cell viability and tissue production over an extended duration.…”