Biology subjects

Crotts, S.

Publications and source records attributed to Crotts, S..

4 recordsLinked to original sources

bioRxiv2025

Th1 effector CD4 T cells rely on IFN-γ production to induce alopecia areata

Alopecia areata (AA) is an autoimmune disease that is clinically characterized by hair loss and histologically by a peribulbar infiltrate of CD8 and CD4 T cells. Prior studies have focused on the role of CD8 T cells in the development of AA; however, the role of CD4 T cells remains unclear. Here, we demonstrate that CD4 T cells from the skin draining lymph nodes (SDLN) of AA mice transferred disease into recipient mice. Further, these cells exhibited a T-helper type 1 (Th1) effector transcriptional and phenotypic profile. The pathogenic activity of these CD4 T cells was dependent upon the presence of endogenous CD8 T cells and host IFN-{gamma} responsiveness. Targeted deletion of CD4 T cell-mediated production of IFN-{gamma} abrogated the ability of this cell population to transfer disease. Together, these data provide mechanistic insights into pathways that lead to AA development, strengthening our understanding of the disease and inviting studies into exploring novel therapeutic strategies for human patients.

immunology↗

bioRxiv2023

Generative design approach to combine architected Voronoi foams with porous collagen scaffolds to create a tunable composite biomaterial

Regenerative biomaterials for musculoskeletal defects must address multi-scale mechanical challenges. We are developing biomaterials for craniomaxillofacial bone defects that are often large and irregularly shaped. These require close conformal contact between implant and defect margins to aid healing. While we have identified a mineralized collagen scaffold that promotes mesenchymal stem cell osteogenic differentiation in vitro and bone formation in vivo, its mechanical performance is insufficient for surgical translation. We report a generative design approach to create scaffold-mesh composites by embedding a macro-scale polymeric Voronoi mesh into the mineralized collagen scaffold. The mechanics of architected foam reinforced composites are defined by a rigorous predictive moduli equation. We show biphasic composites localize strain during loading. Further, planar and 3D mesh-scaffold composites can be rapidly shaped to aid conformal fitting. Voronoi-based composites overcome traditional porosity-mechanics relationship limits while enabling rapid shaping of regenerative implants to conformally fit complex defects unique for individual patients.

bioengineering↗

bioRxiv2021

Repair of critical-size porcine craniofacial bone defects using a collagen-polycaprolactone composite biomaterial

Regenerative medicine approaches for massive craniomaxillofacial bone defects face challenges associated with the scale of missing bone, the need for rapid graft-defect integration, and challenges related to inflammation and infection. Mineralized collagen scaffolds have been shown to promote mesenchymal stem cell osteogenesis due to their porous nature and material properties, but are mechanically weak, limiting surgical practicality. Previously, these scaffolds were combined with 3D-printed polycaprolactone mesh to form a scaffold-mesh composite to increase strength and promote bone formation in sub-critical sized porcine ramus defects. Here, we compare the performance of mineralized collagen-polycaprolactone composites to the polycaprolactone mesh in a critical-sized porcine ramus defect model. While there were no differences in overall healing response between groups, our data demonstrated broadly variable metrics of healing regarding new bone infiltration and fibrous tissue formation. Abscesses were present surrounding some implants and polycaprolactone polymer was still present after 9-10 months of implantation. Overall, while there was limited successful healing, with 2 of 22 implants showed substantial levels of bone regeneration, and others demonstrating some form of new bone formation, the results suggest targeted improvements to improve repair of large animal models to more accurately represent craniomaxillofacial bone healing. Notably, strategies to increase osteogenesis throughout the implant, modulate the immune system to support repair, and employ shape-fitting tactics to avoid implant micromotion and resultant fibrosis. Improvements to the mineralized collagen scaffolds involve changes in pore size and shape to increase cell migration and osteogenesis and inclusion or delivery of factors to aid vascular ingrowth and bone regeneration.

bioengineering↗

bioRxiv2020

Tissue Engineered Vascularized Patient-Specific Temporomandibular Joint Reconstruction in a Yucatan Pig Model

PurposePediatric temporomandibular joint (TMJ) reconstruction occurs as a result of acquired, developmental, and/or congenital conditions. Current pediatric reconstruction options are limited. The aim of this project was to develop a proof of principle porcine model for a load bearing, customized 3-dimensional (3D) printed and BMP2-coated scaffold implanted in a pedicled (temporal) flap as a regenerative approach to pediatric TMJ mandibular condyle reconstruction. Materials and MethodsScaffolds were custom designed and 3D printed based on porcine computed tomography and absorbed with BMP2. Two operations occured: (1) implantation of scaffold in temporalis muscle to establish vascularity, and six weeks later, (2) unilateral condylectomy and rotation of the vascularized scaffold (with preservation of superficial temporal artery) onto mandibular ramus defect and secured with titanium screws. At 6 months post-implantation, the pigs were sacrified. The experimental side (muscle-scaffold) and the control side (unoperated condyle) were individually harvested at 6 months and evaluated by clinical, mechanical, radiographic, and qualitative/histologic methods. ResultsScaffolds maintained physical properties similar in appearance to unoperated condyles. The vascularized scaffolds had bone formation at edges and adjacent to scaffold-bone interface. New bone was visible in scaffold. Condyle height on the reconstructed side was 68% and 78% of the control side. Reconstructed condyle stiffness was between 20% and 45% of the control side. ConclusionIn our porcine model, customized 3D printed TMJ scaffolds impregnanted with BMP2 and implanted in and pedicled on temporalis muscle has the ability to (1) reconstruct a TMJ defect model, (2) maintain appropriate condylar height and upper airway diameter, and (3) generate new bone, without impacting functional outcomes.

bioengineering↗