Periodic Reporting for period 1 - PACMAN (sPatially and environmentAlly aCtuable nancoMposite hydrogels towArds Nervous system repair)
Periodo di rendicontazione: 2022-07-01 al 2024-06-30
The overall objective of the project is to develop nanocomposite hydrogels with the potential to improve outcomes in nervous system repair. In order to accomplish this objective, a multidisciplinary project was undertaken in order to fabricate multifunctional, nanocomposite hydrogels. These were created by engineering across length scales- from the nanoscale (mesoporous silica nanoparticles) to the microscale (polyethylene (PEG) microgels) and up to the macroscale (granular hydrogel scaffolds). The ability to engineer scaffolds across length scales increases the potential to create multifunctional scaffolds. Therefore, PACMAN sought to develop nanocomposite hydrogels that have engineered degradation, payload release, mechanical properties, porosity, and cellular infiltration properties. Due to the many applications of hydrogels in tissue engineering, the results of PACMAN have the potential to be exploited across many areas of tissue engineering beyond just nervous system repair.
The main achievement of PACMAN was the development, characterization, and reproducible fabrication of multiscale hydrogels composed of di-sulfide mesoporous silica nanoparticles crosslinked PEG microgels into granular hydrogels. These nanocomposite hydrogels degrade in the presence of glutathione, release small molecule payloads, have mechanical properties that can be tuned, display intrinsic porosity, and promote cellular infiltration into the hydrogels. In addition to this main achievement, several other nanoparticle and hydrogel systems were developed. These include DNA aptamer conjugated nanoparticles, where the aptamers were shown to retain their function, release of payloads from bulk PEG hydrogels, and nanocomposite hydrogels that remove toxins from solution.
The results for PACMAN include the synthesis and characterization of di-sulfide mesoporous silica nanoparticles that contain thiols to crosslink PEG microgels, rheological measurements showing the ability to alter mechanical properties of hydrogels, engineering degradation in the presence of glutathione over 72 hours, payload release from nanocomposite hydrogels, and cellular infiltration into the crosslinked granular hydrogels. Additionally, payload release was shown to be controlled when loaded into nanoparticles as opposed to directly into hydrogels, and, using surface chemistry modified mesoporous silica nanoparticles, toxins in solutions could be scavenged in hydrogels.