Biology subjects

Davidson, M. D.

Publications and source records attributed to Davidson, M. D..

5 recordsLinked to original sources

bioRxiv2025

Synovial fibroblasts support vascular function in an acute injury-on-a-chip model

Most patients who sustain an acute joint injury develop degenerative joint disease, or osteoarthritis (OA). Animal models have informed the design of OA therapeutics; however, no disease-modifying therapy has successfully translated to human patients. Thus, there is a strong motivation to develop humanized in vitro platforms to fill a critical gap in knowledge of disease progression post-injury. Here, we develop an acute injury-on-a-chip model of the synovium, a vascularized, joint-lining tissue that has been implicated in OA progression and as a key driver of joint disease. We apply this chip-based system to investigate crosstalk between endothelial cells, lining an engineered vessel, and synovial fibroblasts, embedded within an extracellular matrix hydrogel. Our data indicate that synovial fibroblasts, rather than initiating disease, attempt to support and maintain vascular function in the presence of acute inflammation (i.e., interleukin-1{beta}). Such knowledge may provide new targets for OA therapeutics, preventing the progression from joint injury to disease in patients. TeaserIn the presence of inflammation, a hallmark of acute injury, synovial fibroblasts work to maintain vascular health.

bioengineering↗

bioRxiv2023

Microinterfaces in bicontinuous hydrogelsguide rapid 3D cell migration

Cell migration is critical for tissue development and regeneration but requires extracellular environments that are conducive to motion. Cells may actively generate migratory routes in vivo by degrading or remodeling their environments or may instead utilize existing ECM microstructures or microtracks as innate pathways for migration. While hydrogels in general are valuable tools for probing the extracellular regulators of 3D migration, few have recapitulated these natural migration paths. Here, we developed a biopolymer-based (i.e., gelatin and hyaluronic acid) bicontinuous hydrogel system formed through controlled solution immiscibility whose continuous subdomains and high micro-interfacial surface area enabled rapid 3D migration, particularly when compared to homogeneous hydrogels. Migratory behavior was mesenchymal in nature and regulated by biochemical and biophysical signals from the hydrogel, which was shown across various cell types and physiologically relevant contexts (e.g., cell spheroids, ex vivo tissues, in vivo tissues). Our findings introduce a new design that leverages important local interfaces to guide rapid cell migration.

bioengineering↗

bioRxiv2022

Injectable MSC Spheroid and Microgel Granular Composites for Engineering Cartilage Tissue

Articular cartilage is important for joint function, yet it can be damaged due to disease or trauma. Cartilage lacks natural healing processes and current clinical treatments are limited in their ability to form functional cartilage for repair. Here, we reimagine cartilage tissue engineering with an approach that combines aggregates of adult MSCs (spheroids) with hydrogel microparticles (microgels) to form granular composites that are injectable, permit cell-cell contacts for chondrogenesis, allow spheroid fusion and growth, and undergo interparticle crosslinking post-injection via light for stability. We use simulations and experimental analyses to establish the importance of initial MSC spheroid to microgel volume ratios in granular composites that balance mechanical support with tissue growth. Long-term chondrogenic cultures of granular composites produce engineered cartilage tissue within the range of native properties, which can be further enhanced via MSC/chondrocyte co-cultures. Altogether, we have developed a new strategy of injectable granular composites for engineering cartilage tissue.

bioengineering↗

bioRxiv2021

Programmable and Contractile Materials Through Cell Encapsulation in Fibrous Hydrogel Assemblies

The natural extracellular matrix (ECM) within tissues is physically contracted and remodeled by cells, allowing the collective shaping of functional tissue architectures. Synthetic materials that facilitate self-assembly similar to natural ECM are needed for cell culture, tissue engineering, and in vitro models of development and disease. To address this need, we develop fibrous hydrogel assemblies that are stabilized with photocrosslinking and display fiber density dependent strain responsive properties (strain-stiffening, alignment). Encapsulated mesenchymal stromal cells locally contract low fiber density assemblies, resulting in macroscopic volumetric changes with increased cell densities and moduli. Due to properties such as shear-thinning and self-healing, assemblies can be processed into microtissues with aligned ECM deposition or through extrusion bioprinting and photopatterning to fabricate constructs with programmed shape changes due to cell contraction. These materials provide a synthetic approach to mimic features of natural ECM, which can now be processed for applications in biofabrication and tissue engineering.

bioengineering↗

bioRxiv2020

3D bioprinting of high cell-density heterogeneous tissue models through spheroid fusion within self-healing hydrogels

Cellular models are needed to study human development and disease in vitro, including the screening of drugs for toxicity and efficacy. However, current approaches are limited in the engineering of functional tissue models with requisite cell densities and heterogeneity to appropriately model cell and tissue behaviors. Here, we develop a new bioprinting approach to transfer spheroids into self-healing support hydrogels at high resolution, which enables their patterning and fusion into high-cell density microtissues of prescribed spatial organization. As an example application, we bioprint induced pluripotent stem cell-derived cardiac microtissue models with spatially controlled cardiomyocyte and fibroblast cell ratios to replicate the structural and functional features of scarred cardiac tissue that arise following myocardial infarction, including reduced contractility and irregular electrical activity. The bioprinted in vitro model is combined with functional readouts to probe how various pro-regenerative microRNA treatment regimes influence tissue regeneration and recovery of function as a result of cardiomyocyte proliferation. This method is useful for a range of biomedical applications, including the development of precision models to mimic diseases and for the screening of drugs, particularly where high cell densities and heterogeneity are important.

bioengineering↗