Vining Lab at Penn Dental Medicine
and Penn Engineering
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 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, leadership, diversity, and equity. 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.
Current Areas of Investigation
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 (Vining and Mooney, 2017). 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 monocyte fate and develop strategies to target myeloid inflammation in vivo. Monocytes are a type of white blood cells that impact the local immune response by producing cytokines and differentiating into phagocytic and antigen-presenting cells, like macrophages and dendritic cells.
- We first investigated this concept in hematopoietic malignancies that result in myelofibrosis (Vining, K.H., et al., Nature Materials, 2022). The data revealed changes of viscoelasticity in diseases associated with myelofibrosis, more than changes in stiffness alone, regulates inflammation and differentiation of monocytes, and is targetable by a PI3K-gamma inhibitor.
- This work has potential broad applications in fibrotic and inflammatory diseases.
Vining, K.H., Mooney, D.J. (2017). Mechanical forces direct stem cell behavior in development and regeneration. Nature Reviews Molecular Cell Biology 18, 728-742. PMCID: PMC5803560
Vining, K.H.*, Marneth, A.*, Adu-Berchie, K., Grolman, J., Tringides, C.M. , Liu, Y., Wong, W., Pozdnyakova, O., Severgnini, M., Stafford, A., Duda, G., Mullally, A., Hodi, F.S., Wucherpfennig, K., Mooney D.J., A mechanical checkpoint regulates monocyte differentiation in fibrotic niches. Nature Materials, July 2022. https://doi.org/10.1038/s41563-022-01293-3. *Authors contributed equally.
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 resistance in solid tumors, and to develop new strategies to boost the clinical response rate of immune checkpoint blockade.
Monocytes are recruited to tumors and affect the immune microenvironment. Immature monocytes are largely considered immunosuppressive in nature, and support tumor evasion of anti-tumor immunity, whereas differentiated antigen-presenting cells, such as dendritic cells, are associated with improved clinical responses to immunotherapies. However, underlying factors that direct immature myeloid cells in tumors remain elusive.
The Vining Lab investigates whether mechanical cues regulate the fate of myeloid cells to alter the immune microenvironment in oral squamous cell carcinoma and fibrotic disease. Solid tumors are surrounded by a rigid stroma of ECM with collagen fibers that is more rigid than healthy tissue. In addition to stiffness, tumor stromal ECM exhibits relative fluid-like viscous and solid-like elastic properties, i.e., viscoelasticity.
- Vining earned a NIH K99/R00 Pathway to Independence Award from the NIDCR to investigate the relationship between mechanical regulation and monocyte fates in oral cancer through his post-doctoral position at Dana-Farber Cancer Institute in Boston, MA and starting his own lab at Penn Dental Medicine and Penn Engineering.
- We dissect mechanical regulation of myeloid cells to overcome immune resistance and boost efficacy of immunotherapies in head and neck cancer.
- We use a three-dimensional artificial ECM to study the impact of mechanical cues on differentiation human monocytes, analysis of clinical samples, and a mouse model of oral cancer.
- These studies have potential to lead to new treatments for HNSCC to over-come evasion of anti-tumor immunity.
Our work investigates how mechanical properties of ECMdirects the immune fate of bone marrow niche cells. The immune system develops in the bone marrow, which is viscoelastic, exhibiting properties of both a solid and fluid. Dr. Vining earned a NIH K08 Mentored Clinical Scientist Career Development Award from the NIDCR to support his Ph.D. in David Mooney’s lab at Harvard University to develop artificial systems with human cells to study how the mechanical resistance of ECM can direct the immune fate of mesenchymal stromal cells (MSCs) (Vining, K.H., et al., 2018). 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. More fluid-like, viscous matrix was associated with immunomodulatory expression of MSCs, which is consistent with homeostasis in healthy bone marrow. Further, collaborative projects have demonstrated how programmable materials can be used to enhance persistence and immunomodulation of MSCs (Mao, A.S., et al., 2019), and to enhance licensing of MSCs for immunomodulation (Pujana-Gonzalez, A., Vining, K.H., et al., 2020).
Vining, K.H., Stafford, A., Mooney, D.J. (2019) Sequential modes of crosslinking tune viscoelasticity of cell-instructive hydrogels. Biomaterials, 188, 187-197. PMCID: 30366219
Mao, A.S., Ozkale, B., Shah, N.J., Vining, K.H., Descombes, T., Zhang, L., Scadden, D.T., Weitz, D.A., Mooney, D.J. (2019) Programmable microencapsulation for enhanced mesenchymal stem cell persistence and immunomodulation. Proceedings of the National Academy of Science, 116 (31) 15392-15397. PMCID: PMC6681761
Gonzalez-Pujana A*, Vining K.H.*, Zhang DKY, Santos-Vizcaino E, Igartua M, Hernandez RM, Mooney DJ. Multifunctional biomimetic hydrogel systems to boost the immunomodulatory potential of mesenchymal stromal cells. Biomaterials. 2020 Oct;257:120266. PMCID: PMC7477339. *Authors contributed equally
Untreated tooth decay in permanent teeth is the most common health condition worldwide, affecting over 3.5 billion patients according to the Global Burden of Disease 2017. Dental treatments directly cost $298 billion annually in 2010, with a total economic impact of an estimated $442 billion. There is an unmet clinical need to better understand how physical changes of ECM impact inflammation and how to promote repair and regeneration for clinical applications, such as dental pulpitis, periodontal disease, and orthodontic tooth movement. Dentists place hundreds of millions of dental fillings per year in the U.S. alone, which can result in dental pain or infection after the restoration is placed.
The Vining Lab aims to develop next-generation mechano- and biomaterial-based therapeutics that interface with oro-dental tissues for healing and regeneration (US Patent issued US11224679). This project will identify myeloid populations involved in dental pulp injury and will develop biomaterials to target pulpal inflammation.
- We hypothesize that irreversible dental pulp injury results in fibrosis of the extracellular matrix and increased pro-inflammatory myeloid cells.
- We correlate the mechanical properties of inflamed dental tissues by micro-rheology and atomic force microscopy with immune cell populations identified by flow cytometry, next-generation sequencing, and immuno-histochemistry.
- We develop biomaterials strategies to target dental pulp inflammation using experimental immuno-mechanical therapies, including a combination of chemical and immune checkpoint drugs and cellular therapies. Candidate therapies are tested in a model of dental pulp injury (Vining et al., Advanced Materials 2018)
- We also develop new artificial extracellular matrix hydrogels for regeneration of stem-cell derived dental tissues. Adult stem and progenitor cells are encapsulated in hydrogel with defined biochemical and mechanical cues to program develop and regeneration of craniofacial epithelial and mesenchymal tissues (Vining, Lombaert et al., Biomaterials, 2019).
- The goal of these studies is to develop new materials to drive dental regeneration by modulating immunomodulatory factors to enhance pulpal healing and dentinogenesis, and to explore through collaboration other applications in salivary glands, periodontal disease, and orthodontic tooth movement.
A.D. Celiz, K.H. Vining, D.J. Mooney. Methods and compositions for dental tissue repair and/or regeneration. US Patent 11,224,679. Issued 2022.
Vining, K.H., Scherba, J., Bever, A., Alexander, M., Celiz, A.D., Mooney, D.J. (2018) Synthetic Light-Curable Polymeric Materials Provide a Supportive Niche for Dental Pulp Stem Cells. Advanced Materials, 30, 1704486. PMCID: PMC5788014
Vining, K.H., Lombaert, I.M., et al. (2019). Neurturin-containing laminin matrices support innervated branching epithelium from adult epithelial salispheres. Biomaterials, 216, 119245. PMCID: PMC6720117
Kyle Vining, DDS, PhD — Principal Investigator
Assistant Professor of Preventive and Restorative Sciences, Penn Dental Medicine, and Materials Science and Engineering, Penn Engineering
Dr. Kyle Vining holds a PhD in bioengineering from Harvard University, DDS from the University of Minnesota School of Dentistry, and BS in biomedical engineering from Northwestern University. He was a postdoctoral scientist at the Dana-Farber Cancer Institute prior to joining Penn. He also previously completed a fellowship in the Medical Research Scholars Program at the National Institutes of Health. Dr. Kyle was the first faculty member recruited to the new Center for Innovation & Precision Dentistry (CiPD) at Penn Dental Medicine. He is jointly appointed in Penn Dental and Penn Engineering. His research investigates mechanical regulation of tissue inflammation in bone marrow disease and head and neck cancer. He is also developing strategies to target inflammation and promote tissue repair and regeneration in oral and craniofacial diseases. Dr. Kyle Vining maintains an active clinical practice in restorative and cosmetic dentistry at Penn Dental Family Practice at University City. Dr. Kyle relocated to Philadelphia to start his career in academic dentistry and research. He previously was an associate dentist at a private group specialty clinic in the Boston area during his PhD and post-doctoral training. He is joined by his wife, daughter, and small dog. He enjoys cycling to work in Philadelphia, as well as exploring the trails and bike paths in the area.
Mia Ruiz, M.S. – Research Specialist
Mia received her M.S. in Biology at the University of Texas Rio Grande Valley in South Texas where she also received her B.S. in Biology and minor in Chemistry. In her graduate research, she worked under Dr. Robert K. Dearth in a lab with a main interest in female puberty and neuroendocrinological changes using zebrafish as a model animal. She has also served as a teaching assistant for various biology courses. Her research experience is enhanced by her dream of practicing dentistry. She also enjoys listening to podcasts and trying out new recipes.
Il-Chul Yoon, Ph.D. – Penn Dental and Penn Engineering Postdoctoral Fellow
Dr. Il-Chul Yoon is a postdoctoral fellow with a strong background in chemistry, chemical engineering, biology, and physics. His knowledge and expertise were honed during his Ph.D. studies under the supervision of Professor James D. E. T. Wilton-Ely, and he has since gained extensive research and teaching experience in the field of chemistry. This experience has enabled him to tackle scientific challenges with innovative approaches and produce practical solutions for society. Currently, his research interests are focused on understanding the molecular and cellular mechanisms of the human body, as well as developing effective strategies for delivering biomolecules to specific target regions, such as the oral microenvironment. In his leisure time, he enjoys visiting a museum or gallery, watching movies, and engaging in physical exercise.
Asal Tavakoli – Penn Materials Science PhD Student
Asal is a first-year Materials Science and Engineering PhD student who obtained a Bachelor’s degree from the University of Tehran. During her undergraduate studies, she worked on photocatalysis, but her interest shifted to biomaterials. She is passionate about developing new materials and exploring their applications.
Kexin Zhang, M.S. – Penn Materials Science PhD student
Kexin is a first-year Ph.D. student in Materials Science and Engineering. Before she joined the Vining lab in April 2023, she received her B.Eng. degree from Sun Yat-sen University in Macromolecular Materials and Engineering, and her M.S. degree from Northwestern University in Materials Science and Engineering. Her current research focuses on the fabrication and characterization of biomaterials for cell behavior modulation.
Shuchen Zhang — Penn Bioengineering Master’s Student
Shuchen is a first-year Bioengineering masters student. Before coming to Penn, she received a B.S in Molecular, Cell and Developmental Biology from UCLA. Her research focuses on elucidating the molecular and genetic reasons behind mechanical regulation of immune cells. In her free time, she likes to listen to acappella songs.
Doris Chen, BS — Penn Dental Medicine Student
Doris Chen is a second-year dental student at the University of Pennsylvania School of Dental Medicine. She graduated from the University of North Carolina at Chapel Hill with a Bachelor of Science degree in Quantitative Biology and minors in Statistics and Chemistry. Doris’s experience as a research assistant at the Sondek Lab at UNC sparked her passion for research. In her current project, she is investigating the effects of inflammation on dental pulp stem cells with different mechanical conditions under the mentorship of Dr. Vining, with the goal of developing a drug delivery system for patients with pulpitis. Doris believes that innovation and research are crucial in dentistry, as new technology has the potential to push the field forward and benefit many patients.
Jedtanut Thussananutiyakul, B.D.S – Penn Dental DScD Student and Ortho Resident
Jedtanut Thussananutiyakul is a first-year Doctor of Science in Dentistry (DScD) and Orthodontics resident in the School of Dental Medicine at the University of Pennsylvania. He graduated from Chulalongkorn University, Bangkok, Thailand as a Doctor of Dental Surgery. He is interested in researching to gain more insights into oral biology and enhance new relating treatments.
Roene Nasr — Penn Undergraduate Student
Roene Nasr is a third-year undergraduate student at the University of Pennsylvania’s College of Arts and Sciences, where she is pursuing a degree in Neuroscience (BS) and minors in Chemistry and French. She is a recipient of the CURF Fall 2022 College Alumni Society Board of Managers and Presidents Undergraduate Research Grant, which has allowed her to engage in research on regenerative dentistry, working under the mentorship of Dr. Kyle Vining. In her current project, Roene focuses on the regulation of dental pulp stem cells (DPSCs) in fibrotic hydrogels by furthering her knowledge of how inflammatory white blood cells affect DPSCs in such fibrotic hydrogels with defined biochemical and mechanical cues. Her interests in chemistry and French stem from her recognition of how elaborate the world becomes when we adjust our field of view: by zooming in on the effect of individual atoms and molecules on more extensive systems, and synonymously, zooming out on the power of language and communication. Upon completion of her undergraduate studies, Roene intends to apply to dental school to further her knowledge of dentistry and progress toward a career as both a dentist and researcher.