Jellyfish have emerged as a source of next generation collagen that is an attractive alternative to existing sources, such as bovine and porcine, due to a plentiful supply and providing a safer source through lack of bovine spongiform encephalopathy (BSE) transmission risk and potential viral vectors, both of which could be transmitted to humans. Here we compare collagen implantable sponges derived for the first time from the Rhizostoma pulmo jellyfish. A further novelty for the research was that there was a comparison for sponges that were either uncrosslinked or crosslinked using 1‐ethyl‐3‐(3‐dimethylaminopropyl) carbodiimide hydrochloride (EDC), and an assessment on how this affected resorption, as well as their biocompatibility compared to bovine type I collagen sponges. The scaffolds were prepared and examined using sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS PAGE) and scanning electron microscopy (SEM). The samples were implanted in adult male Wistar rats for in vivo experimentation. Both crosslinked and uncrosslinked jellyfish collagen sponges showed a significant reduction in histopathology scores over the course of the study, whereas the bovine collagen sponge scores were not significantly reduced. Both jellyfish collagen sponges and the bovine sponge were tolerated well by the hosts, and a recovery was visible in all samples, suggesting that R. pulmo jellyfish‐derived collagen could offer compelling biocompatibility with wound healing applications. We also demonstrate that noncrosslinked samples could be safer with better resorption times than crosslinked samples. © 2017 The Authors Journal of Biomedical Materials Research Part B: Applied Biomaterials Published by Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 106B: 1524–1533, 2018.

Osteoarthritis (OA) is a multifactorial disease leading to degeneration of articular cartilage, causing morbidity in approximately 8.5 million of the UK population. As the dense extracellular matrix of articular cartilage is primarily composed of collagen, cartilage repair strategies have exploited the biocompatibility and mechanical strength of bovine and porcine collagen to produce robust scaffolds for procedures such as matrix-induced chondrocyte implantation (MACI). However, mammalian sourced collagens pose safety risks such as bovine spongiform encephalopathy, transmissible spongiform encephalopathy and possible transmission of viral vectors. This study characterised a non-mammalian jellyfish (Rhizostoma pulmo) collagen as an alternative, safer source in scaffold production for clinical use. Jellyfish collagen demonstrated comparable scaffold structural properties and stability when compared to mammalian collagen. Jellyfish collagen also displayed comparable immunogenic responses (platelet and leukocyte activation/cell death) and cytokine release profile in comparison to mammalian collagen in vitro. Further histological analysis of jellyfish collagen revealed bovine chondroprogenitor cell invasion and proliferation in the scaffold structures, where the scaffold supported enhanced chondrogenesis in the presence of TGFβ1. This study highlights the potential of jellyfish collagen as a safe and biocompatible biomaterial for both OA repair and further regenerative medicine applications.

Accurate disease models are essential for understanding disease pathogenesis and for developing new therapeutics. As stem cells are capable of self-renewal and differentiation, they are ideally suited both for generating these models and for obtaining the large quantities of cells required for drug development and transplantation therapies. Jellyfish collagen is showing great promise as a next generation matrix enabling improved outcomes in 2D and 3D cell culture and regenerative medicine. Here, we report the potential of jellyfish collagen for culturing induced pluripotent stem cell derived cell lines (iPSCs) for modeling human diseases. Jellyfish collagen from Rhizostoma pulmo (Jellagen R) was evaluated for the growth and viability of iPSC-derived microgliallike cells (iMGL) comparing to cells cultured on rat tail collagen 1, laminin-511 and tissue culture plastic. Viability was measured using MTT, XTT, Alamar Blue and Annexin V, since this last assay has the aim of evaluating the onset of apoptosis. Cell ramification was measured using Neurotracker software and ramification measured on the InCucyte S3 TM. Cell surface receptor expression was quantified using flow cytometry. Microglia markers used for immunocytochemistry were IBA1, CD11b, TREM2, TMEM119, and P2RY12. We report that iPSC-derived microglia can be successfully cultured on Jellagen R jellyfish collagen demonstrating a more ramified cell morphology compared to cells cultured on mammalian rat tail collagen I and comparable to Laminin-511.

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Marine origin polymers represent a sustainable and natural alternative to mammal counterparts regarding the biomedical application due to their similarities with proteins and polysaccharides present in extracellular matrix (ECM) in humans and can reduce the risks associated with zoonosis and overcoming social- and religious-related constraints. In particular, collagen-based biomaterials have been widely explored in tissue engineering scaffolding applications, where cryogels are of particular interest as low temperature avoids protein denaturation. However, little is known about the influence of the parameters regarding their behavior, i.e., how they can influence each other toward improving their physical and chemical properties. Factorial design of experiments (DoE) and response surface methodology (RSM) emerge as tools to overcome these difficulties, which are statistical tools to find the most influential parameter and optimize processes. In this work, we hypothesized that a design of experiments (DoE) model would be able to support the optimization of the collagen-chitosan-fucoidan cryogel manufacturing. Therefore, the parameters temperature (A), collagen concentration (B), and fucoidan concentration (C) were carefully considered to be applied to the Box–Behnken design (three factors and three levels). Data obtained on rheological oscillatory measurements, as well as on the evaluation of antioxidant concentration and adenosine triphosphate (ATP) concentration, showed that fucoidan concentration could significantly influence collagen-chitosan-fucoidan cryogel formation, creating a stable internal polymeric network promoted by ionic crosslinking bonds. Additionally, the effect of temperature significantly contributed to rheological oscillatory properties. Overall, the condition that allowed us to have better results, from an optimization point of view according to the DoE, were the gels produced at −80 °C and composed of 5% of collagen, 3% of chitosan, and 10% fucoidan. Therefore, the proposed DoE model was considered suitable for predicting the best parameter combinations needed to develop these cryogels.