Immuno-Mechanobiology, Precision Bio-Interfaces, and Translational Dental Medicine –
Bridging the gap between materials science, biology, and dental medicine to bring next-generation innovations to the clinic, Dr. Kyle Vining, DDS, PhD, practices restorative and cosmetic dentistry at Penn Dental Family Practice and leads a multi-disciplinary team of scientists and engineers investigating mechanical regulation of inflammation in cancer and regeneration. The Vining Lab values excellence, collaboration, and leadership. The Vining Lab’s overall goal is to discover new physical mechanisms of disease and to develop materials and therapies. Our lab investigates how physical forces regulate immune and tissue cell function in cancer, fibrosis, and regeneration. We develop next-generation biomaterials, targeted RNA nanomedicines, and mechanotherapies to transform oral and systemic healthcare.
Current Areas of Investigation
Investigating Immuno-Mechanical Regulation of Fibrosis
The Vining Lab investigates the impact of viscoelasticity on inflammation in fibrotic tissues and develops new immunotherapies in cancer.
- We utilize an artificial ECM to dissect a mechanical checkpoint of myeloid cell fate and develop strategies to control myeloid inflammation in vivo. Monocytes are a type of white blood cell that impacts the local immune response by producing cytokines and differentiating into phagocytic and antigen-presenting cells, like macrophages and dendritic cells. (Lin et al. APL Bioengineering 2025)
- We first investigated this concept in hematopoietic malignancies that result in myelofibrosis, revealing that changes in viscoelasticity regulate inflammation and differentiation of monocytes, and is targetable by a PI3K-gamma inhibitor. (Vining et al., Nat Mater 2022)
- We are applying these findings to investigate mechano-licensing of dendritic cells for priming T cell immunity. (Chen et al. bioRxiv 2026)
- This work is supported by the NIH/NIGMS R35, the American Cancer Society, Hartwell Foundation, and has broad applications in fibrotic and inflammatory diseases.
Targeting Immuno-Mechanical Regulation of Head and Neck Cancer
The Vining Lab investigates how these mechanical cues regulate tumor invasion and immune evasion in oral cancer. Specifically, we study how the viscoelasticity of the surrounding matrix regulates oral cancer spheroid growth and influences the behavior of recruited immune cells within the tumor microenvironment.
- We developed biophysical-based models of solid tumor growth. (Mollenkopf et al. Soft Matter 20250, Li et al. Soft Matter 2026) Further, we dissect the immuno-mechanical mechanisms that direct both tumor cell progression and the immunosuppressive fate of recruited myeloid cells.
- Supported by the NIH/NIDCR K99/R00 Pathway to Independence Award—our goal is to uncover novel mechanotherapeutic targets to overcome immune resistance and improve treatments for oral squamous cell carcinoma.
Mechanobiology of Immunomodulatory Mesenchymal Stromal Cells and Fibroblasts
Our work investigates how mechanical properties of the extracellular matrix (ECM) direct the immune fate of stromal cells across various tissue niches. The blood system develops in the bone marrow, which is viscoelastic, exhibiting properties of both a solid and fluid.
- To study this, an artificial fibrillar ECM was fabricated with interpenetrating networks of type-I collagen and chemically-modified polysaccharides. Viscoelasticity was specifically tuned independent of other material properties across a physiologic range of bone marrow stiffness. (Vining et al. Biomat 2019, Nat Mater 2022, Zhang et al. ACS Appl Bio Materials 2025)
- A more fluid-like, viscous matrix was associated with immunomodulatory expression of mesenchymal stromal cells (MSCs) (Lim et al. PNAS 2024), which is consistent with homeostasis in healthy bone marrow.
- Our hydrogel co-culture models of MSCs with hematopoietic cells led to a new NIH/NCI R61 award to develop neighborhood-based models of bone marrow malignancies.
- Further, we investigate into how matrix mechanics govern immune homeostasis in oral tissues. Recently, we demonstrated that matrix stiffness directly governs fibroblast-driven immune responses in gingival tissues. (Makkar et al. Adv Mater 2025, bioRxiv 2026) We aim to uncover novel mechanotherapeutic targets for treating oral inflammation.
Engineering Biomaterials and Targeted Nanotherapeutics for Oral Repair
The Vining Lab is developing translatable biomaterial strategies to restore oral health and promote tissue regeneration.
- We develop piperazine-derived bisphosphonate-ionizable lipid nanoparticles customized for targeting local RNA delivery to mineralized tissues. (Yoon et al. Angewandte Chemie, 2025; Liu et al. bioRxiv 2026)
- We utilize rational material design to create adhesives that bond strongly to mineralized tissues like dentin and enamel. (Luo et al. Adv Health Mater 2025)
- We develop programmable hydrogels that sustain large scale mechanical deformation. (Luo et al. ACS Materials Letters 2026)
- We characterized the material properties of developing oral hard tissues to better understand development and genetic defects in mineralization. (Jiang et al. ACS App Mater Inter 2025)
These technologies bridge the gap between materials science, immunology, and clinical restorative dentistry.
