Gelatin-Based Polymers Can Be Processed to Highly Resilient Biocompatible Porous Hydrogel Scaffolds for Soft Tissue Regeneration Applications

Tissue regeneration relies on the mechanical properties of the surrounding environment, and it has already been shown that mechanostimulation is highly dependent on the stiffness of the native biological tissue. The main advantage of injectable hydrogels in medical applications is their ability to be delivered through minimally invasive techniques. Natural polymer-based hydrogels have been widely used in biomedical applications, due to their high biocompatibility, low immunogenicity, and similarity to soft tissues. However, the crucial combination of low stiffness with high resilience has not been achieved for natural polymers. The current study focuses on the development of novel gelatin-based injectable hydrogels for soft tissue regeneration applications, elucidating the effects of the formulation parameters on the resilience, microstructure, biocompatibility, and mechanical properties. Non-foamed hydrogels demonstrated resilience of at least 95%, while porous hydrogels maintained resilience above 90%, allowing them to withstand mechanical stresses and dynamic conditions within the body. The adjustable modulus of these hydrogels provides the necessary flexibility to mimic the mechanical properties of soft and very soft tissues, without compromising resilience. Environmental Scanning Electron Microscopy (ESEM) observations of the porous hydrogels indicated round interconnected pore structures, desired for cell migration and nutrient flow. Biocompatibility tests on fibroblasts and pre-adipocytes confirmed high biocompatibility, both directly and indirectly. In summary, structuring these new hydrogels for achieving adjustable stiffness, along with the excellent resilience and biocompatibility, is expected to enable this new technology to fit various soft tissue regeneration applications.