Optimization of Gelatin Methacryloyl Hydrogel Properties through an Artificial Neural Network Model.

Gelatin methacryloyl (GelMA) hydrogels are promising materials for tissue engineering applications due to their biocompatibility and tunable properties. However, the time-consuming process of preparing GelMA hydrogels with desirable properties for specific biomedical applications limits their clinical use. Visible-light-induced cross-linking is a well-known method for the preparation of GelMA hydrogels; however, a comprehensive investigation on the influence of critical parameters such as Eosin Y (EY), triethanolamine (TEA), and N-vinyl-2-pyrrolidone (NVP) concentrations on the stiffness and gelation time has yet to be performed. In this study, we systematically investigated the effect of these critical parameters on the stiffness and gelation time of GelMA hydrogels. We developed an artificial neural network (ANN) model with three input variables, EY, TEA, and NVP concentrations, and two output variables, Young's modulus and gelation time, derived from our experimental design. Through the alteration of individual chemical concentrations, [EY] between 0.005 and 0.5 mM and [TEA] and [NVP] between 10 and 1000 mM, we studied the impact of these alterations on the real-time values of stiffness and gelation time. Furthermore, we demonstrated the validity of the ANN model in predicting the properties of GelMA hydrogels. We also studied cell survival to establish nontoxic concentration ranges for each component, enabling safer use of GelMA hydrogels in relevant biomedical applications. Our results showed that the ANN model can accurately predict the properties of GelMA hydrogels, allowing for the synthesis of hydrogels with desirable stiffness for various biomedical applications. In conclusion, our study provides a comprehensive library that characterizes the stiffness and gelation time and demonstrates the potential of the ANN model to predict these properties of GelMA hydrogels depending on the critical parameters. The ANN models developed here can facilitate the optimization of GelMA hydrogels with the most efficient mechanical properties that resemble a native extracellular matrix and better address the need in the in vivo microenvironment. The approach of this study is to bring research about the synthesis of GelMA hydrogels to a new level where the synthesis of these hydrogels can be standardized with minimum cost and effort.

Immunological response of polysaccharide nanogel-incorporating PEG hydrogels in an in vivo diabetic model.

Cell-based therapies hold significant advantages in comparison with the traditional drug-based or injection-based treatments. However, for long-term functional cellular implants, immune acceptance must be established. To accomplish the acceptance of the implanted cells, various biomaterial systems have been studied. Nanogels have shown great potential for modulation of cellular microenvironments, acting as a physical barrier between the immune system and the implant. However, internalization of nano-scale materials by implanted cells is not desirable and is yet to be overcome. In this study, we incorporated acrylate modified cholesterol-bearing pullulan (CHPOA) nanogels into poly (ethylene glycol) diacrylate (PEGDA) hydrogels through covalent crosslinking, where we used visible light-induced photopolymerization. We characterized morphology and swelling properties of CHPOA incorporated PEG composite hydrogels using FE-SEM and gravimetric analysis. Also, we investigated the biocompatibility properties of composite hydrogels in vivo, where we used both healthy and diabetic mice. We induced diabetes in mice using a low dose streptozotocin (STZ) injections and implanted composite hydrogels in both diabetic and healthy mice through subcutaneous route. Immune cell infiltration of the retrieved tissue was examined through histological analysis, where we observed minimum immune response levels of 0-2 rareness, according to ISO standard of biological evaluation of medical devices. Our observation suggests that the composite hydrogel developed here can be used to introduce nanostructured domains into bulk hydrogels and that this system has potential to be used as immunologically acceptable composite material in cellular therapy without internalization of nanoparticles.

Neovascularization of engineered tissues for clinical translation: Where we are, where we should be?

One of the key challenges in engineering three-dimensional tissue constructs is the development of a mature microvascular network capable of supplying sufficient oxygen and nutrients to the tissue. Recent angiogenic therapeutic strategies have focused on vascularization of the constructed tissue, and its integration in vitro; these strategies typically combine regenerative cells, growth factors (GFs) with custom-designed biomaterials. However, the field needs to progress in the clinical translation of tissue engineering strategies. The article first presents a detailed description of the steps in neovascularization and the roles of extracellular matrix elements such as GFs in angiogenesis. It then delves into decellularization, cell, and GF-based strategies employed thus far for therapeutic angiogenesis, with a particularly detailed examination of different methods by which GFs are delivered in biomaterial scaffolds. Finally, interdisciplinary approaches involving advancement in biomaterials science and current state of technological development in fabrication techniques are critically evaluated, and a list of remaining challenges is presented that need to be solved for successful translation to the clinics.