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 to radically disrupt the dental industry and ultimately transform oral, dental and craniofacial healthcare.
Investigating Immuno-Mechanical Regulation of Fibrosis
Fibrosis and remodeling of extracellular matrix (ECM) are involved in many diseases affecting health, such as tumors, wound healing, and chronic inflammation. During fibrosis, tissues undergo changes in their viscoelastic properties, i.e., how they resist deformation like a solid and dissipate stress over time like a fluid. Independent of stiffness, an applied stress relaxes rapidly in a more viscous, liquid-like matrix, whereas in a more elastic, solid-like material, stress relaxes slowly. The Vining Lab investigates the impact of viscoelasticity on inflammation in fibrotic tissues and develops new immunotherapies in cancer.
Targeting Immuno-Mechanical Regulation of Head and Neck Cancer
Head and neck squamous cell carcinoma (HNSCC) is the seventh most common cancer in the world and presents in most patients with locally advanced disease. There is an unmet clinical need to identify mechanisms of treatment resistance in solid tumors and to develop new strategies to boost the clinical response rate of immunotherapies.
Solid tumors are surrounded by a rigid, collagen-rich stroma of extracellular matrix (ECM) that exhibits distinct viscoelastic properties—behaving with both fluid-like (viscous) and solid-like (elastic) characteristics. 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.
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. For example, the immune 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.
We found that a more fluid-like, viscous matrix was associated with immunomodulatory expression of mesenchymal stromal cells (MSCs), which is consistent with homeostasis in healthy bone marrow. Furthermore, collaborative projects have demonstrated how programmable materials and matrix stiffness can be used to regulate immunomodulatory genes, enhance cellular persistence, and boost the licensing of MSCs for immunomodulation.
Building on these principles, we are expanding our investigation into how matrix mechanics govern immune homeostasis in oral and craniofacial environments. Recently, we demonstrated that matrix stiffness directly governs fibroblast-driven immune responses in gingival tissues. By understanding how the mechanical stiffening of the gingival ECM during periodontal disease alters the immunomodulatory behavior of local fibroblasts, we aim to uncover novel mechanotherapeutic targets for treating periodontal inflammation and promoting tissue regeneration.
Engineering Biomaterials and Targeted Nanotherapeutics for Oral Repair
The Vining Lab is developing translatable biomaterial strategies to restore oral health and promote tissue regeneration. A major focus is designing targeted nanotherapeutics to deliver mRNA and other biologics directly to the bone and dental microenvironments. We are also engineering multi-functional, light-curable polymeric materials and tough adhesive hydrogels for intraoral adhesion and targeted drug delivery.
