Biology subjects

Davenport Huyer, L.

Publications and source records attributed to Davenport Huyer, L..

5 recordsLinked to original sources

bioRxiv2026

Age and sex alter the immune response in a chronic fibrosis model via changes in T cell and macrophage phenotype

The foreign body response (FBR) is an immune mediated event that occurs with every material implant. The extent of the fibrosis is dependent on many factors including the biomaterial design, tissue location, and host factors such as age, sex, ancestry, diet. There are known clinical outcomes of implants dependent on age and sex, including increased fibrosis and implant failure in aged and female patients. As the population ages, there is a growing need to understand how aging affects the FBR, and how preclinical models can capture this to guide biomaterial design. Here, we investigated how chronic fibrosis in a murine model of the FBR is altered by two biological factors: age and sex. We investigated changes in fibrosis using a volumetric muscle loss (VML) injury model coupled with polycaprolactone (PCL) or polyethylene (PE) microparticle implants. Fibrosis was quantified through gene expression, microscopic analysis of histologic sections, and the corresponding immune response measured via gene expression and flow cytometry data. We found gene expression differences with immune pathways enriched in female mice, and microscopy revealed collagen birefringence area increased in young male mice. Both the innate and adaptive immune response were altered by age and sex via T cell and macrophage phenotype, and the effects of aging differed between sexes. These results reveal both variables contribute to discrepant outcomes in both fibrosis and the local immune response to synthetic material implants. This demonstrates a clear need to understand and account for the influence of biological factors in biomaterial design.

bioengineering↗

bioRxiv2026

Tissue Injury and Biomaterial Treatment Modulate Tumor Growth and Response to Immunotherapy

Immunotherapies have transformed cancer care; however, tumor intrinsic and extrinsic factors contribute to high variability in therapeutic responses. While tissue injuries can impact cancer recurrence and metastatic spread, little is known about their potential to effect immune checkpoint blockade (ICB) response. In this study, we reveal that distal traumatic muscle injury accelerated progression and impaired adjuvant ICB response of multiple murine tumors. This injury-induced accelerated tumor growth coincided with decreased intra-tumoral density and effector phenotype of tumor-reactive CD8+ T cells and relied on communication through a shared draining lymph node. Enhancing injury repair using a biological scaffold abrogated the injury-induced accelerated tumor growth in an interleukin-4-dependent manner and improved ICB response. In a retrospective cohort analysis of breast cancer patients undergoing ICB treatment, biological scaffold implantation following mastectomy was associated with increased overall survival. This work suggests that injury-driven immune dysfunction may contribute to cancer progression and ICB resistance, but enhancing wound healing with pro-regenerative biomaterials may offer a viable strategy for mitigating adverse cancer outcomes, particularly in the setting of adjuvant and neoadjuvant ICB.

cancer biology↗

bioRxiv2025

Persistent glycolysis defines the foreign body response to polymeric implants.

Non-degradable polymeric implantable medical devices are a mainstay of modern healthcare but can frequently lead to severe complications. These complications are largely attributable to the foreign body response (FBR), which is characterized by excessive inflammation and fibrosis in response to implanted materials. The pathologic mechanisms underpinning the FBR remain elusive; however, metabolism is increasingly regarded as a critical regulator of innate immune function. We conducted comprehensive metabolic profiling of implant-associated macrophages and multinucleated giant cells in response to the subcutaneous implantation of clinically relevant implantable materials in a mouse model of implant fibrosis. Leveraging novel metabolic characterization methods for analysis of both metabolic dependence and enzyme expression in heterogeneous peri-implant tissues, we demonstrate that peri-implant macrophages are glycolytic at least up to six weeks post-implantation. Glycolytically dependent peri-implant macrophages expression of glucose transporter 1 (GLUT1) increased temporally and with proximity to the implant-tissue interface. Paired rate-limiting metabolic enzyme expression analysis showed notable increases in biosynthetic pathways (G6PD and ACC1), matched with increased mitochondrial staining intensity in GLUT1Hi cells at chronic timepoints, which were not notable at early timepoints. Notably, we identified a glycolytic dependence of multinucleated macrophages associated with polymeric materials: these cells expressed higher levels of GLUT1 than mononuclear macrophages of comparable metabolic phenotype. Our findings highlight GLUT1-dependent glycolysis as the definitive metabolic system used by peri-implant macrophages and multinucleated cells in the FBR, highlighting this pathway as a potential target for the development of novel therapeutic approaches.

immunology↗

bioRxiv2021

Biomaterials direct functional B cell response in a material specific manner

B cells are an adaptive immune target of biomaterials development in vaccine research but despite their role in wound healing have not been studied in tissue engineering and regenerative medicine. We evaluated the B cell response to biomaterial scaffold materials implanted in a muscle wound; a biological extracellular matrix (ECM) and synthetic polyester polycaprolactone. In the local muscle tissue, small numbers of B cells are recruited in response to tissue injury and biomaterial implantation. ECM materials induced plasmablasts in lymph nodes and antigen presentation in the spleen while the synthetic PCL implants delayed B cell migration and induced an antigen presenting phenotype. In muMt- mice lacking B cells, the fibrotic response to the synthetic biomaterials decreased. Immunofluorescence confirmed antigen presenting B cells in fibrotic tissue surrounding silicone breast implants. In sum, the adaptive B cell immune response to biomaterial depends on composition and induces local, regional and systemic immunological changes.

bioengineering↗

bioRxiv2019

Enhancing senior high school student engagement and academic performance using an inclusive and scalable inquiry-based program

The multi-disciplinary nature of science, technology, engineering and math (STEM) careers often renders difficulty for high school students navigating from classroom knowledge to post-secondary pursuits. Discrepancies between the knowledge-based high school learning approach and the experiential approach of undergraduate studies leaves some students disillusioned by STEM. We present Discovery, a semester-long inquiry-focused learning model delivered by STEM graduate students in collaboration with high school educators, in the context of biomedical engineering. Entire classes of high school STEM students representing diverse cultural and socioeconomic backgrounds engaged in iterative, problem-based learning designed to emphasize critical thinking concomitantly within the secondary school and university environments. Assessment of grades and survey data suggested positive impact of this learning model on students STEM pursuits, notably in under-performing cohorts, as well as repeating cohorts that engage in the program on more than one occasion. Discovery presents a scalable platform blurring the divide between secondary and post-secondary learning, providing valuable learning opportunities and capturing cohorts of students that might otherwise be under-engaged in STEM.

scientific communication and education↗