Impact of Annealing Chemistry on the Properties and Performance of Microporous Annealed Particle Hydrogels.

Microporous annealed particle (MAP) hydrogels are a promising class of in situ-forming scaffolds for tissue repair and regeneration. While an expansive toolkit of annealing chemistries has been described, the effects of different annealing chemistries on MAP hydrogel properties and performance have not been studied. In this study, we address this gap through a controlled head-to-head comparison of poly(ethylene glycol) (PEG)-based MAP hydrogels that were annealed using tetrazine-norbornene and thiol-norbornene click chemistry. Characterization of material properties revealed that tetrazine click annealing significantly increases MAP hydrogel shear storage modulus and results in slower in vitro degradation kinetics when microgels with a higher cross-link density are used. However, these effects are muted when the MAP hydrogels are fabricated from microgels with a lower cross-link density. In contrast, in vivo testing in murine critical-sized calvarial defects revealed that these differences in physicochemical properties do not translate to differences in bone volume or calvarial defect healing when growth-factor-loaded MAP hydrogel scaffolds are implanted into mouse calvarial defects. Nonetheless, the impact of tetrazine click annealing could be important in other applications and should be investigated further.

Impact of PEG sensitization on the efficacy of PEG hydrogel-mediated tissue engineering.

While poly(ethylene glycol) (PEG) hydrogels are generally regarded as biologically inert blank slates, concerns over PEG immunogenicity are growing, and the implications for tissue engineering are unknown. Here, we investigate these implications by immunizing mice against PEG to stimulate anti-PEG antibody production and evaluating bone defect regeneration after treatment with bone morphogenetic protein-2-loaded PEG hydrogels. Quantitative analysis reveals that PEG sensitization increases bone formation compared to naive controls, whereas histological analysis shows that PEG sensitization induces an abnormally porous bone morphology at the defect site, particularly in males. Furthermore, immune cell recruitment is higher in PEG-sensitized mice administered the PEG-based treatment than their naive counterparts. Interestingly, naive controls that were administered a PEG-based treatment also develop anti-PEG antibodies. Sex differences in bone formation and immune cell recruitment are also apparent. Overall, these findings indicate that anti-PEG immune responses can impact tissue engineering efficacy and highlight the need for further investigation.

Greatest 'HITS': A new tool for tracking impacts at the National Institute of Environmental Health Sciences.

Evaluators of scientific research programs have several tools to document and analyze products of scientific research, but few tools exist for exploring and capturing the impacts of such research. Understanding impacts is beneficial because it fosters a greater sense of accountability and stewardship for federal research dollars. This article presents the High Impacts Tracking System (HITS), a new approach to documenting research impacts that is in development at the National Institute of Environmental Health Sciences (NIEHS). HITS is designed to help identify scientific advances in the NIEHS research portfolio as they emerge, and provide a robust data structure to capture those advances. We have downloaded previously un-searchable data from the central NIH grants database and developed a robust coding schema to help us track research products (going beyond publication counts to the content of publications) as well as research impacts. We describe the coding schema and key system features as well as several development challenges, including data integration, development of a final data structure from three separate ontologies, and ways to develop consensus about codes among program staff.