Hydrogels are an attractive class of biomaterials in tissue engineering due to their inherently compatible properties for cell culture. Gelatin methacryloyl (GelMA) has shown significant promise in the fields of tissue engineering and drug delivery, as its physical properties can be precisely tuned depending on the specific application. There is a growing appreciation for the interaction between biomaterials and cells of the immune system with the increasing usage of biomaterials for in vivo applications. Here, we addressed the current lack of information regarding the immune-modulatory properties of photocrosslinked GelMA. We investigated the ability of human mononuclear cells to mount inflammatory responses in the context of a GelMA hydrogel platform. Using lipopolysaccharide to stimulate a pro-inflammatory immune response, we found tumor necrosis factor-α (TNF-α) expression was suppressed in GelMA culture conditions. Our findings have important implications on the future use of GelMA, and potentially similar hydrogels, and highlight the significance of investigating the potential immune-modulatory properties of biomaterials.

Immunity to previously encountered viruses can alter response to unrelated pathogens. We reasoned that similar mechanism may also involve SARS-CoV-2 and thereby affect the specificity and the quality of the immune response against the virus. Here, we employed high-throughput next generation phage display method to explore the link between antibody immune response to previously encountered antigens and spike (S) glycoprotein. By profiling the antibody response in COVID-19 naïve individuals with a diverse clinical history (including cardiovascular, neurological, or oncological diseases), we identified 15 highly antigenic epitopes on spike protein that showed cross-reactivity with antigens of seasonal, persistent, latent or chronic infections from common human viruses. We observed varying degrees of cross-reactivity of different viral antigens with S in an epitope-specific manner. The data show that pre-existing SARS-CoV-2 S1 and S2 cross-reactive serum antibody is readily detectable in pre-pandemic cohort. In the severe COVID-19 cases, we found differential antibody response to the 15 defined antigenic and cross-reactive epitopes on spike. We also noted that despite the high mutation rates of Omicron (B.1.1.529) variants of SARS-CoV-2, some of the epitopes overlapped with the described mutations. Finally, we propose that the resolved epitopes on spike if targeted by re-called antibody response from SARS-CoV-2 infections or vaccinations can function in chronically ill COVID-19 naïve/unvaccinated individuals as immunogenic targets to boost antibodies augmenting the chronic conditions. Understanding the relationships between prior antigen exposure at the antibody epitope level and the immune response to subsequent infections with viruses from a different strain is paramount to guiding strategies to exit the COVID-19 pandemic.

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Design and fabrication of implants that can perform better than autologous bone grafts remain an unmet challenge for the hard tissue regeneration in craniomaxillofacial applications. Here, we report an integrated approach combining additive manufacturing with supramolecular chemistry to develop acellular mineralizing 3D printed scaffolds for hard tissue regeneration. Our approach relies on an elastin-like recombinamer (ELR) coating designed to trigger and guide the growth of ordered apatite on the surface of 3D printed nylon scaffolds. Three test samples including a) uncoated nylon scaffolds (referred to as “Uncoated”), b) ELR coated scaffolds (referred to as “ELR only”), and c) ELR coated and in vitro mineralized scaffolds (referred to as “Pre-mineralized”) were prepared and tested for in vitro and in vivo performance. All test samples supported normal human immortalized mesenchymal stem cell adhesion, growth, and differentiation with enhanced cell proliferation observed in the “Pre-mineralized” samples. Using a rabbit calvarial in vivo model, ‘Pre-mineralized’ scaffolds also exhibited higher bone ingrowth into scaffold pores and cavities with higher tissue-implant integration. However, the coated scaffolds (“ELR only” and “Pre-mineralized”) did not exhibit significantly more new bone formation compared to “Uncoated” scaffolds. Overall, the mineralizing coating offers an opportunity to enhance integration of 3D printed bone implants. However, there is a need to further decipher and tune their immunologic response to develop truly osteoinductive/conductive surfaces.