Biology subjects

Baugh, N. J.

Publications and source records attributed to Baugh, N. J..

3 recordsLinked to original sources

bioRxiv2026

Lipid Network Crosslinked Hydrogels: Controlling MaterialDynamics Across Multiple Length Scales Through Lipid Movement

Control over network dynamics at different length scales is a feature of natural materials challenging to replicate in synthetic hydrogels. Hydrogel viscoelasticity is commonly controlled by tuning the kinetics of reversible crosslinks; however, this strategy inherently links the resulting macroscale and nanoscale dynamics of the individual network components. Taking inspiration from biological materials that feature lipids as structural elements, we introduce Lipid Network Crosslinked (LINC) hydrogels that exploit the mobility of individual lipids within self-assembled liposomes as covalent, network-crosslinking points. These mobile, covalent crosslinks increase hydrogel stress relaxation rates over 20-fold compared to polymer-only hydrogels with equivalent crosslinking chemistries and stiffnesses. We demonstrate that liposome design parameters, including degree of surface functionalization and tail saturation, provide a means to independently control the macroscale storage moduli and stress relaxation behavior. Finally, as an application where control over network dynamics at different length scales is critical, we placed cell-adhesive ligands onto more mobile or less mobile network elements. Human neural progenitor cells cultured within LINC hydrogels of identical macroscale viscoelasticity significantly altered their phenotype in response to nanoscale ligand dynamics. These results establish LINC hydrogels as biomimetic materials that leverage nanoscale lipid mobility within a macroscale polymeric network to control dynamics at multiple length scales.

bioengineering↗

bioRxiv2025

Tuning viscoelasticity of dynamic covalent hydrogels for human tissue modeling

The development of three-dimensional (3D) in vitro tissue culture models is critical for biomedical research. Hydrogel-based systems have become a preferred scaffold for 3D models, as they have tunable viscoelastic properties, which are well-known to influence cell morphology and function. In particular, reversible hydrogel crosslinks formed through dynamic covalent chemistry (DCC) can introduce viscoelastic behavior including stress relaxation. However, traditional strategies to increase stress-relaxation rates in DCC gels rely on faster bond kinetics, resulting in faster erosion rates that prevent their use for long-term 3D culture. As an alternative strategy, we explore the use of molecular parameters (specifically molecular weight and degree of functionalization) to independently control the stiffness and stress relaxation behavior while preventing rapid erosion. As demonstration, we develop and validate a modified theoretical model of gel viscoelasticity applied to a two-component DCC gel composed of modified hyaluronic acid and elastin-like protein. Finally, we utilize this tunable gel platform to explore the impact of scaffold viscoelasticity on encapsulated human neural progenitor cells. In summary, this work expands the molecular design space of DCC hydrogels to achieve tunable viscoelastic properties for 3D in vitro models.

bioengineering↗

bioRxiv2023

Custom-engineered hydrogels for delivery of human iPSC-derived neurons into the injured cervical spinal cord

Cervical damage is the most prevalent type of spinal cord injury clinically, although few preclinical research studies focus on this anatomical region of injury. Here we present a combinatorial therapy composed of a custom-engineered, injectable hydrogel and human induced pluripotent stem cell (iPSC)-derived deep cortical neurons. The biomimetic hydrogel has a modular design that includes a protein-engineered component to allow customization of the cell-adhesive peptide sequence and a synthetic polymer component to allow customization of the gel mechanical properties. In vitro studies with encapsulated iPSC-neurons were used to select a bespoke hydrogel formulation that maintains cell viability and promotes neurite extension. Following injection into the injured cervical spinal cord in a rat contusion model, the hydrogel biodegraded over six weeks without causing any adverse reaction. Compared to cell delivery using saline, the hydrogel significantly improved the reproducibility of cell transplantation and integration into the host tissue. Across three metrics of animal behavior, this combinatorial therapy significantly improved sensorimotor function by six weeks post transplantation. Taken together, these findings demonstrate that design of a combinatorial therapy that includes a gel customized for a specific fate-restricted cell type can induce regeneration in the injured cervical spinal cord.

bioengineering↗