Pilot Study: Zwitterionic Conditioning of the Decompressive Craniectomy Site for Early Cranioplasty Feasibility

Background: Early cranioplasty after decompressive craniectomy (DC) for moderate-to-severe traumatic brain injury (TBI) improves functional recovery. However, patient candidacy is limited by persistent brain swelling, soft-tissue inflammation, and fibrotic wound remodeling. Zwitterion (ZI) hydrogels exhibit antifouling and anti-inflammatory properties that may improve the DC wound microenvironment. We hypothesize that ZI hydrogel application at the DC site attenuates TBI-associated biomarkers and improves motor recovery in rodents. Methods: Adult CD1 mice were randomized to sham, TBI, TBI/DC, or TBI/DC/ZI hydrogel (hereafter referred to as ZI hydrogel) groups to quantify serum GFAP, NfL, and UCH-L1 by ELISA at 24 hours. Adult Long Evans rats underwent the same interventions to assess ZI-dependent motor recovery using beam-walk time and limb slips normalized to baseline at days 7 and 14. Results: TBI significantly elevated serum GFAP and UCH-L1 versus sham ( P = .0014 and .0471). Both TBI/DC and ZI hydrogel normalized GFAP, NfL, and UCH-L1 to sham-comparable levels; however, only ZI hydrogel significantly reduced NfL ( P = .0256) and UCH-L1 ( P = .0200) versus TBI/DC. Beam-walk testing showed no significant post-TBI motor deterioration in ZI hydrogel rats, whereas TBI/DC rats exhibited persistent deficits in crossing time and limb slips at days 7 and 14. Conclusions: ZI hydrogel application at the time of DC reduced TBI-specific serum biomarkers and improved motor recovery in a rodent moderate-to-severe TBI model. These findings support further investigation of ZI hydrogels as adjunctive therapy to attenuate neuroinflammation and facilitate earlier, safer cranioplasty after DC.