Abstract
Current surgical techniques to treat articular cartilage defects fail to produce a satisfactory long-term repair of the tissue. Regenerative approaches show promise in their ability to generate hyaline cartilage using biomaterials in combination with stem cells. However, the difficulty of seamlessly integrating the newly generated cartilage with the surrounding tissue remains a likely cause of long-term failure. To begin to address this integration issue, our strategy exploits a biological enzyme (microbial transglutaminase) to effect bioadhesion of a gelatin methacryloyl implant to host tissue. Mechanical characterization of the bioadhesive material shows that enzymatic crosslinking is compatible with photocrosslinking, allowing for a dual-crosslinked system with improved mechanical properties, and a slower degradation rate. Biocompatibility is illustrated with a 3D study of the metabolic activity of encapsulated human adipose derived stem cells. Furthermore, enzymatic crosslinking induced by transglutaminase is not prevented by the presence of cells, as measured by the bulk modulus of the material. Adhesion to human cartilage is demonstrated ex vivo with a significant increase in adhesive strength (5.82 ± 1.4 kPa as compared to 2.87 ± 0.9 kPa, p < 0.01) due to the addition of transglutaminase. For the first time, we have characterized a bioadhesive material composed of microbial transglutaminase and GelMA that can encapsulate cells, be photo crosslinked, and bond to host cartilage, taking a step toward the integration of regenerative implants.
Highlights
Effective long-term treatment of damaged articular cartilage is a significant unmet medical challenge [1,2,3]
The viscosity of Gelatin methacryloyl (GelMA) combined with transglutaminase was measured via rheology at a shear rate of 100 s−1 after different stages of incubation at 37◦C to evaluate the timedependent impact of transglutaminase on the material in the absence of photocrosslinking (Figure 2A)
Though all materials undergo a significant increase in viscosity over 200 min compared to controls, this only holds practical significance for 10% GelMA, which sees a sharp increase in viscosity after 160 min incubation (∼145 mPa.s to 705 mPa.s) as the material begins to form a weak gel
Summary
Effective long-term treatment of damaged articular cartilage is a significant unmet medical challenge [1,2,3]. Whilst current surgical treatments to repair cartilage defects can provide relief in the short term, they often result in mechanically weak and inferior fibrocartilage, and see deterioration in the long term [9]. Surgical techniques utilizing cell-free scaffolds, often combined with microfracture, have seen clinical results improve in the short and mid-term, and scaffolds utilizing autologous chondrocytes are on the market in some European and Asian countries [9, 12]. Information on the long-term efficacy of cell-free approaches is lacking in the literature, and this remains to be seen for cell-seeded scaffold approaches, though a 5-year follow-up of treatment with autologous chondrocytes cultured on porcine collagen membrane showed promising results relative to microfracture [10, 12, 13]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
