Biology subjects

Griffin, K. H.

Publications and source records attributed to Griffin, K. H..

3 recordsLinked to original sources

bioRxiv2026

Bioorthogonal Tethering of FGF18 to Annealed Microgel Scaffolds Enhances Cartilage Repair

Articular cartilage damage often progresses to osteoarthritis (OA), a degenerative joint disease characterized by chronic pain, limited mobility, and reduced quality of life. Tissue engineering approaches using poly (ethylene glycol) (PEG)-based hydrogels offer tunable mechanical properties and bioactive functionalization, yet the influence of surface charge on cartilage regeneration remains underexplored. Moreover, recombinant fibroblast growth factor 18 (FGF18) has successfully improved cartilage tissue thickness in clinical trials, but required high dosages and recurring injections may limit compliance. Here, we developed a granular microgel-based platform with bioorthogonally tethered FGF18 to evaluate the interplay of microgel surface charge and growth factor presentation on chondrogenesis. Azide groups were incorporated onto the microgel surfaces to enable site specific FGF18 conjugation across microgel scaffolds with distinct surface charges. When seeded with mesenchymal stromal cells, microgel scaffolds functionalized with FGF18 outperformed their unmodified counterparts, evidenced by higher GAG content, collagen content, and compressive modulus. In a murine microfracture model, anionic and zwitterionic microgel scaffolds tethered with FGF18 increased cartilage regeneration compared to nonionic microgels. We detected increased collagen II content within defects treated with tethered FGF18 microgel scaffolds. This work demonstrates the role of surface charge and growth factor presentation in directing cell behavior and tissue repair, advancing the design of biomaterials for cartilage regeneration. HIGHLIGHTSO_LICovalent tethering of FGF18 to microgel surface enables localized bioactivity C_LIO_LIFGF18 tethered microgel scaffolds enhance extracellular matrix deposition and chondrogenic differentiation of murine mesenchymal stromal cells in vitro C_LIO_LILocalized FGF18 presentation improves cartilage tissue formation and mechanical properties in vivo, with anionic and zwitterionic microgel scaffolds outperforming nonionic scaffolds C_LIO_LIFGF18 presentation is a more potent stimulus than microgel surface charge for cartilage regeneration C_LI

bioengineering↗

bioRxiv2025

Controlled delivery of immunomodulatory factors for mineralized tissue formation in an inflammatory microenvironment

Mesenchymal stromal cells (MSCs) are a promising cell-based therapy for bone healing, contributing to tissue regeneration through direct differentiation or immunomodulatory factor secretion. However, diseases that feature chronic or dysregulated inflammation, such as non-union fractures and osteonecrosis of the jaw (ONJ), have proven difficult to treat with current MSC-based approaches. Here, we investigated whether controlled delivery of immunomodulatory factors would allow MSCs to simultaneously undergo osteogenic differentiation and modulate inflammation. We first used a Design of Experiments approach to identify the type and concentrations of immunomodulatory factors (IMFs) that most effectively induce concurrent pro-regenerative macrophages and MSC osteogenic differentiation, then loaded these IMFs into polymeric microparticles for controlled release. Through our in vitro models, we demonstrated that microparticles releasing IL-10 and IL-4 promote naive MSC osteogenesis and modulate immune response, even in chronic, physiologically relevant, inflammatory conditions. We then applied this approach to an in vivo rat model of ONJ as a clinically relevant example of such conditions. We observed clinically relevant sex-based differences in inflammation and bone formation that have not yet been reported. These data represent key findings that will facilitate the reversal of diseases that are linked to chronic bone loss and inflammation, such as ONJ.

bioengineering↗

bioRxiv2023

Conductive microgel annealed scaffolds enhance myogenic potential of myoblastic cells

Bioelectricity is an understudied phenomenon to guide tissue homeostasis and regeneration. Conductive biomaterials may capture native or exogenous bioelectric signaling, but incorporation of conductive moieties is limited by cytotoxicity, poor injectability, or insufficient stimulation. Microgel annealed scaffolds are promising as hydrogel-based materials due to their inherent void space that facilitates cell migration and proliferation better than nanoporous bulk hydrogels. We generated conductive microgels from poly(ethylene) glycol and poly(3,4-ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) to explore the interplay of void volume and conductivity on myogenic differentiation. PEDOT:PSS increased microgel conductivity over 2-fold while maintaining stiffness, annealing strength, and viability of associated myoblastic cells. C2C12 myoblasts exhibited increases in the late-stage differentiation marker myosin heavy chain as a function of both porosity and conductivity. Myogenin, an earlier marker, was influenced only by porosity. Human skeletal muscle derived cells exhibited increased Myod1, IGF-1, and IGFBP-2 at earlier timepoints on conductive microgel scaffolds compared to non-conductive scaffolds. They also secreted higher levels of VEGF at early timepoints and expressed factors that led to macrophage polarization patterns observed during muscle repair. These data indicate that conductivity aids myogenic differentiation of myogenic cell lines and primary cells, motivating the need for future translational studies to promote muscle repair.

bioengineering↗