title: Biocompatibility of poly(ethylene glycol)-based hydrogels in the brain: an analysis of the glial response across space and time.
abstract: Poly(ethylene glycol) or PEG-based hydrogels provide a useful methodology for tissue engineering and the controlled-release of drugs within the central nervous system (CNS). To be successful, the local neuroinflammatory response to an implant must be well understood. Toward this end, the focus was to examine the localized recruitment and activation of microglia and astrocytes following implantation of PEG-based hydrogels in the brain. Because they are of clinical relevance and may impact brain tissue differently, hydrogels with different mass loss profiles were examined. At all time points, a needle penetration in sham animals evoked a greater astrocytic response than hydrogel conditions. The astrocyte response that ensued varied with degradation rate. An attenuated response was present in more slowly degrading and nondegrading conditions. Relative to sham, hydrogel conditions attenuated the acute microglial response during the week after implant. By 56 days, microglial levels in shams decreased below the observed response in slowly degrading and nondegradable gels, which remained constant overtime. Although the inflammatory response to PEG-based hydrogels was complex depending on degradation rates, the magnitude of the acute microglia response and the long-term astrocyte response were attenuated suggesting the use of these materials for drug and cell delivery to the CNS.
authors.affiliation: Department of Pediatrics, University of Colorado Denver, Aurora, Colorado, USA. kimberly.bjugstad@ucdenver.edu
authors.forename: K B
authors.initials: KB
authors.lastname: Bjugstad
authors.forename: K
authors.initials: K
authors.lastname: Lampe
authors.forename: D S
authors.initials: DS
authors.lastname: Kern
authors.forename: M
authors.initials: M
authors.lastname: Mahoney
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D001672:Biocompatible Materials / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism*; D019245:Compressive Strength / Q000187:drug effects; D020100:Hydrogels / Q000494:pharmacology*; D008297:Male; D017628:Microglia / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D009457:Neuroglia / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D011092:Polyethylene Glycols / Q000494:pharmacology*; D019919:Prosthesis Implantation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
chemical_list: D001672:Biocompatible Materials; D020100:Hydrogels; D011092:Polyethylene Glycols