Biology subjects

Stelzel, J. L.

Publications and source records attributed to Stelzel, J. L..

3 recordsLinked to original sources

bioRxiv2026

Fibroblast signaling influences macrophage-dependent, biomaterial-induced tissue remodeling

The ability to induce tissue regeneration on demand using biomaterials remains a major goal in biomedical research, yet significant challenges persist. Among the most advanced biomaterial models, the nanofiber-hydrogel composite has demonstrated a striking ability to induce soft adipose tissue remodeling at the injection site without incorporating exogenous biological cues.1,2 However, the underlying mechanisms that drive such a tissue response remain unclear. Here, we show that biomaterial-induced tissue remodeling is driven by sustained and controlled inflammation mediated by macrophages in strong communication with fibroblasts. Notably, both pro-inflammatory and anti-inflammatory signals remained elevated during this process in the long-term, challenging the prevailing notion that inflammation opposes remodeling. Using macrophage depletion in mice, we demonstrate that macrophages are essential for this process. Single-cell RNA sequencing further revealed robust fibroblast-to-macrophage signaling, contrasting with the conventional macrophage-to-fibroblast paradigm, and identified unique Spp1 macrophages and Ctla2a fibroblasts within the remodeling niche. These findings provide a comprehensive view of the immune landscape in biomaterial-induced tissue remodeling, highlighting key cellular interactions, prolonged kinetics, and unexpected signaling pathways. By defining key targets and fundamental principles, this work has broad implications for advancing biomaterial-induced tissue regeneration.

bioengineering↗

bioRxiv2025

mRNA lipid nanoparticle-incorporated nanofiber-hydrogel composite generates a local immunostimulatory niche for cancer immunotherapy

Hydrogel materials have emerged as versatile platforms for various biomedical applications. Notably, the engineered nanofiber-hydrogel composite (NHC) has proven effective in mimicking the soft tissue extracellular matrix, facilitating substantial recruitment of host immune cells and the formation of a local immunostimulatory microenvironment. Leveraging this feature, here we report an mRNA lipid nanoparticle (LNP)-incorporated NHC microgel matrix, termed LiNx, by incorporating LNPs loaded with mRNA encoding tumour antigens. Harnessing the potent transfection efficiency of LNPs in antigen-presenting cells (APCs), LiNx demonstrates remarkable immune cell recruitment, antigen expression and presentation, and cellular interaction. These attributes collectively create an immunostimulating milieu and yield a potent immune response achievable with a single dose, comparable to the conventional three-dose LNP immunization regimen. Further investigations reveal that the LiNx not only generates heightened Th1 and Th2 responses but also elicits a distinctive Type 17 T helper cell-mediated response pivotal for bolstering antitumour efficacy. Our findings elucidate the mechanism underlying LiNxs role in potentiating antigen-specific immune responses, presenting a new strategy for cancer immunotherapy.

bioengineering↗

bioRxiv2024

Immunologic comparisons of strain and induction method in an improved mouse model of intrauterine fibrosis

Intrauterine adhesions are growths of fibrotic tissue within the uterine cavity and can arise from a variety of tissue-damaging stimuli. Immune cells are known to mediate fibrotic responses, but specific mechanisms require further elucidation. Here, we compared intrauterine fibrosis development and immune responses across different mouse strains and induction methods. We aimed to identify a consistent and more clinically relevant mouse model of intrauterine fibrosis, whether immune responses differ in response to different stimuli, and which potential key immune cell populations are responsible for intrauterine fibrosis susceptibility. Intrauterine fibrosis induction methods were compared using surgical curettage or transcervically administered chemical (quinacrine) models. Measurements of tissue morphology and collagen gene expression indicate BALB/c mice are more susceptible than C57BL/6 mice to intrauterine fibrosis. In chemically induced BALB/c uterine tissues, gene expression and flow cytometry data show greater pro-inflammatory macrophage responses, implicating a possible role in fibrogenesis consistent with human intrauterine adhesion data. Findings from this study demonstrate the importance of mouse strain selection in studies of intrauterine adhesions. Furthermore, we show that a new hormone-synchronized, chemically induced mouse model can more uniformly and reliably provoke fibrotic tissue response. This model may allow for greater elucidation of mechanisms involved in intrauterine adhesion development, and exploratory therapeutic studies for treatment intervention.

bioengineering↗