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However, inflammatory CNS responses limit these interventions and may worsen outcomes following damage to the CNS. Via the foreign body reaction, macrophages and glial cells trigger a \u201cglial scar\u201d around implants, reducing device performance, scaffold regenerative ability, or drug delivery potential. Previous studies have shown that stiffness of CNS implants significantly affects glial encapsulation, but few studies have investigated materials that truly match brain tissue stiffness. Porous precision\u2010templated scaffolds with uniform, interconnected, 40\u00a0\u00b5m spherical pores have shown favorable healing outcomes and a reduced foreign body reaction (FBR) in numerous soft and hard tissue applications. To quantify the effects of both hydrogel compliance (stiffness) and pore size on glial encapsulation, we implanted poly(2\u2010hydroxyethyl methacrylate\u2010co\u2010glycerol methacrylate) (pHEMA\/GMA) scaffolds of varying stiffness and pore size for 4 weeks in rat brain. We observed reduced astrocyte encapsulation around porous templated scaffolds (PTS) compared to solid hydrogel rods, reduced pro\u2010inflammatory macrophage polarization for softer hydrogels versus stiffer hydrogels, and the presence of new blood vessels, neuronal markers, and neurogenesis within the pores. Utilizing soft, precision\u2010porous hydrogels could provide a strategy for mitigating glial scarring and improving regeneration in implant\u2010based CNS treatments.<\/jats:p>","DOI":"10.1002\/adhm.71522","type":"journal-article","created":{"date-parts":[[2026,8,4]],"date-time":"2026-08-04T05:03:27Z","timestamp":1785819807000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Mechanically Compliant, Precision\u2010Porous Brain Implants Reduce the Foreign Body Reaction and Guide Regeneration"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6173-2000","authenticated-orcid":false,"given":"Ian","family":"Dryg","sequence":"first","affiliation":[{"name":"Department of Bioengineering University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0807-8924","authenticated-orcid":false,"given":"Le","family":"Zhen","sequence":"additional","affiliation":[{"name":"Department of Chemical Engineering University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rebecca","family":"Darrow","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-1964-0561","authenticated-orcid":false,"given":"Savannah","family":"Lawton","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lars","family":"Crawford","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert","family":"Robinson","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1149-4152","authenticated-orcid":false,"given":"Steve","family":"Perlmutter","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3332-3271","authenticated-orcid":false,"given":"James D.","family":"Bryers","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5233-2216","authenticated-orcid":false,"given":"Buddy D.","family":"Ratner","sequence":"additional","affiliation":[{"name":"Department of Bioengineering University of Washington  Seattle Washington USA"},{"name":"Department of Chemical Engineering University of Washington  Seattle Washington USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,8,3]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.17691\/stm2024.16.1.08"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591\u2010018\u20100296\u2010z"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1186\/scrt480"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1080\/17425247.2022.2131768"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.3389\/fbioe.2021.622524"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1088\/1741\u20102560\/10\/6\/066014"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0027554"},{"key":"e_1_2_10_9_1","doi-asserted-by":"crossref","unstructured":"A.Prasad Q. 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