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Grewal, M. G.

Publications and source records attributed to Grewal, M. G..

3 recordsLinked to original sources

Fiber-based hydrogels for designing viscoelastic responses in particle-based biomaterials that support embedded 3D printing

Viscoelastic biomaterials that exhibit biomimetic responses to applied stresses are important in studying physiology and designing biomaterial scaffolds. Particle-based hydrogels offer potential for engineering viscoelasticity through design of both the component microparticles and their processing into bulk particle-based materials. When particles are not crosslinked to one another, particle movements in response to strain can potentially relieve applied stresses and facilitate the materials use in dynamic processes like bioprinting. In particle-based hydrogels based on spherical hydrogel microparticles (HMPs), particle movement is restricted by contacts with immediately adjacent HMPs. In comparison, fiber-based hydrogel systems leverage high-aspect ratio microfiber components with long-range interactions. Here, microfibers with aspect ratios of [~]15:1 length:diameter are used to form particle-based hydrogels to compare how interparticle interactions at increased length scales alter properties compared to particle-based hydrogels based on spherical HMPs. Like particle-based hydrogels formed from spherical HMPs, those formed from fiber HMPs exhibit viscoelasticity, with shear-thinning and self-healing behaviors. But, fiber-based materials allow enhanced control over bulk stress relaxation times (T1/2 [~] 1-100+ s) across a range of applied strains ({sigma} [~] 2.5-50%) in a packing density-dependent fashion. Fiber-based systems relaxed stresses continually and to a greater degree at low strains in comparison to HMP systems. Dynamic interfiber interactions in fiber-based hydrogels also supported embedded printing where perfusable channels can be printed into fiber-based hydrogels stabilized by physical interfiber interactions. Taken together, fiber-based hydrogels offer opportunities for designing complexity into biomaterial scaffolds, including allowing control over viscoelastic properties through hydrogel design and control over heterogeneous 3D structures through embedded printing.

bioengineering↗

Highly porous granular hydrogels reinforced by electrospun hydrogel fibers for long-term stability

Granular hydrogels (GHs) formed from hydrogel microparticles (HMPs) possess inherent, microscale porosity. In GHs including microporous annealed particle (MAP) hydrogels as well as unannealed GHs, increases in pore size and total porosity correlate with enhanced cellular infiltration and growth. However, increased porosity or pore size are typically achieved by decreasing HMP density, reducing interparticle contacts and weakening hydrogel structure. Here, to achieve a highly porous GH without compromising stability, we developed an approach using sacrificial HMPs to achieve high, mesoscale porosity and high-aspect ratio hydrogel fibers to reinforce the scaffold. The use of sacrificial HMPs circumvented the need to decrease packing density, creating GHs with up to 60% porosity. The hydrogel fibers span particles in the porous space, stabilizing the porous structure by enhancing interactions among GH components. Upon 5-10% v/v fiber incorporation, highly porous GHs retained their structure over 28 days of in vivo culture, compared to 4 days in GHs without fibers. These scaffolds supported and promoted endothelial cell growth as porosity increased. Overall, this study presents a stable, highly porous granular scaffold system with high processability and cytocompatibility.

bioengineering↗

Supramolecular fibrous hydrogel augmentation of uterosacral ligament suspension for treatment of pelvic organ prolapse

Uterosacral ligament suspension (USLS) is a common surgical treatment for pelvic organ prolapse (POP). However, the relatively high failure rate of up to 40% underscores a strong clinical need for complementary treatment strategies, such as biomaterial augmentation. Herein, we describe the first hydrogel biomaterial augmentation of USLS in a recently established rat model using an injectable fibrous hydrogel composite. Supramolecularly-assembled hyaluronic acid (HA) hydrogel nanofibers encapsulated in a matrix metalloproteinase (MMP)-degradable HA hydrogel create an injectable scaffold showing excellent biocompatibility and hemocompatibility. The hydrogel can be successfully delivered and localized to the suture sites of the USLS procedure, where it gradually degrades over 6 weeks. In situ mechanical testing 24 weeks post-operative in the multiparous USLS rat model shows the ultimate load (load at failure) to be 1.70 {+/-} 0.36 N for the intact uterosacral ligament (USL), 0.89 {+/-} 0.28 N for the USLS repair, and 1.37 {+/-} 0.31 N for the USLS + hydrogel (USLS+H) repair (n = 8). These results indicate that the hydrogel composite significantly improves load required for tissue failure compared to the standard USLS, even after the hydrogel degrades, and that this hydrogel-based approach could potentially reduce the high failure rate associated with USLS procedures.

bioengineering↗