Matrisomal components involved in regenerative wound healing in axolotl and Acomys: implications for biomaterial development.

Achieving regeneration in humans has been a long-standing goal of many researchers. Whereas amphibians like the axolotl (Ambystoma mexicanum) are capable of regenerating whole organs and even limbs, most mammals heal their wounds via fibrotic scarring. Recently, the African spiny mouse (Acomys sp.) has been shown to be injury resistant and capable of regenerating several tissue types. A major focal point of research with Acomys has been the identification of drivers of regeneration. In this search, the matrisome components related to the extracellular matrix (ECM) are often overlooked. In this review, we compare Acomys and axolotl skin wound healing and blastema-mediated regeneration by examining their wound healing responses and comparing the expression pattern of matrisome genes, including glycosaminoglycan (GAG) related genes. The goal of this review is to identify matrisome genes that are upregulated during regeneration and could be potential candidates for inclusion in pro-regenerative biomaterials. Research papers describing transcriptomic or proteomic coverage of either skin regeneration or blastema formation in Acomys and axolotl were selected. Matrisome and GAG related genes were extracted from each dataset and the resulting lists of genes were compared. In our analysis, we found several genes that were consistently upregulated, suggesting possible involvement in regenerative processes. Most of the components have been implicated in regulation of cell behavior, extracellular matrix remodeling and wound healing. Incorporation of such pro-regenerative factors into biomaterials may help to shift pro-fibrotic processes to regenerative responses in treated wounds.

Cellular Uptake of Modified Mesoporous Bioactive Glass Nanoparticles for Effective Intracellular Delivery of Therapeutic Agents.

Introduction: There has recently been a surge of interest in mesoporous bioactive glass nanoparticles (MBGNs) as multi-functional nanocarriers for application in bone-reconstructive and -regenerative surgery. Their excellent control over their structural and physicochemical properties renders these nanoparticles suitable for the intracellular delivery of therapeutic agents to combat degenerative bone diseases, such as bone infection, or bone cancer. Generally, the therapeutic efficacy of nanocarriers strongly depends on the efficacy of their cellular uptake, which is determined by numerous factors including cellular features and the physicochemical characteristics of nanocarriers, particularly surface charge. In this study, we have systematically investigated the effect of the surface charge of MBGNs doped with copper as a model therapeutic agent on cellular uptake by both macrophages and pre-osteoblast cells involved in bone healing and bone infections to guide the future design of MBGN-based nanocarriers. Methods: Cu-MBGNs with negative, neutral, and positive surface charges were synthesized and their cellular uptake efficiency was assessed. Additionally, the intracellular fate of internalized nanoparticles along with their ability to deliver therapeutic cargo was studied in detail. Results: The results showed that both cell types internalized Cu-MBGNs regardless of their surface charge, indicating that cellular uptake of nanoparticles is a complex process influenced by multiple factors. This similarity in cellular uptake was attributed to the formation of a protein corona surrounding the nanoparticles when exposed to protein-rich biological media, which masks the original nanoparticle surface. Once internalized, the nanoparticles were found to mainly colocalize with lysosomes, exposing them to a more compartmentalized and acidic environment. Furthermore, we verified that Cu-MBGNs released their ionic components (Si, Ca, and Cu ions) in both acidic and neutral environments, leading to the delivery of these therapeutic cargos intracellularly. Conclusion: The effective internalization of Cu-MBGNs and their ability to deliver cargos intracellularly highlight their potential as intracellular delivery nanocarriers for bone-regenerative and -healing applications.

Individuals' Preferences for Esophageal Cancer Screening: A Discrete Choice Experiment.

OBJECTIVES: The increasing incidence of esophageal adenocarcinoma (EAC) and the dismal prognosis has stimulated interest in the early detection of EAC. Our objective was to determine individuals' preferences for EAC screening and to assess to what extent procedural characteristics of EAC screening tests predict willingness for screening participation. METHODS: A discrete choice experiment questionnaire was sent by postal mail to 1000 subjects aged 50 to 75 years who were randomly selected from the municipal registry in the Netherlands. Each subject answered 12 discrete choice questions of 2 hypothetical screening tests comprising 5 attributes: EAC-related mortality risk reduction, procedure-related pain and discomfort, screening location, test specificity, and costs. A multinomial logit model was used to estimate individuals' preferences for each attribute level and to calculate expected rates of uptake. RESULTS: In total, 375 individuals (37.5%) completed the questionnaire. Test specificity, pain and discomfort, mortality reduction, and out-of-pocket costs all had a significant impact on respondents' preferences. The average expected uptake of EAC screening was 62.8% (95% confidence interval [CI] 61.1-64.5). Severe pain and discomfort had the largest impact on screening uptake (-22.8%; 95% CI -26.8 to -18.7). Male gender (ß 2.81; P < .001), cancer worries (ß 1.96; P = .01), endoscopy experience (ß 1.46; P = .05), and upper gastrointestinal symptoms (ß 1.50; P = .05) were significantly associated with screening participation. CONCLUSIONS: EAC screening implementation should consider patient preferences to maximize screening attendance uptake. Based on our results, an optimal screening test should have high specificity, cause no or mild to moderate pain or discomfort, and result in a decrease in EAC-related mortality.