Biology subjects

Huang, M. S.

Publications and source records attributed to Huang, M. S..

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↗

bioRxiv2026

Hydrogel-imposed boundary conditions guide single-lumen neuroepithelial morphogenesis

Three-dimensional (3D) stem cell-based cultures have emerged as promising in vitro model systems for studying human neurodevelopment. Current neural organoid protocols lack well-defined extracellular matrix (ECM) signaling and are limited by the formation of irregular tissue morphologies with multiple organizing centers, in contrast to the single neuroepithelial structure that emerges during embryonic development. This variability limits inter-organoid reproducibility and constrains their utility for modeling early developmental processes. To overcome these limitations, we leverage a materials-based approach to impose dynamic boundary conditions that extrinsically guide the self-organization of human induced pluripotent stem cells (iPSCs). Specifically, we develop a family of hyaluronic acid-elastin-like protein (HELP) hydrogels crosslinked with dynamic covalent bonds that recapitulate key biochemical and biophysical properties of the developing human neural ECM. Within these HELP hydrogels, iPSCs robustly self-organize from a single cell into complex neuroepithelial tissues with a single lumen. By tuning the boundary conditions imposed by the hydrogel, we identify matrix stress relaxation rate and tensional homeostasis as key regulators of single-lumen rosette formation and maintenance. With this hydrogel-enabled system, we identify phenotypic abnormalities in an early neurodevelopmental model of 22q11.2 deletion syndrome. Ultimately, our tunable engineered hydrogel supports the initiation of single-cell derived 3D neuroepithelial tissues, enables investigation into how matrix-imposed boundary conditions guide developmental morphogenesis, and establishes a reproducible platform for disease modeling.

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↗