BACKGROUND: Collagen-heparin sulfate scaffolds have been widely used to repair nerve injury and promote nerve regeneration. Previous research has evaluated scaffold biocompatibility by measuring gliocyte proliferation but not neuronal apoptosis. OBJECTIVE: To explore the biocompatibility of collagen-heparin sulfate scaffold in porcine brain by detecting peripheral neural apoptosis and protein expression. DESIGN, TIME AND SETTING: A randomized, controlled animal experiment was performed at the Laboratory of Neurology, Tongji Hospital Affiliated to Tongji Medical College, Huazhong University of Science and Technology, between March and June, 2008. MATERIALS: Rabbit anti-human Bax, Caspase-3 polyclonal antibody, rat anti-human Bcl-2 polyclonal antibody, streptavidin biotin-peroxidase complex (SABC) immunohistochemical kit, and TUNEL kit (Roche, USA) were used in this study. METHODS: Twenty adult piglets were randomly evenly divided into implantation and control groups. A collagen-heparin sulfate scaffold was implanted from the anterior fontanelle into the brain in the implantation group. The same puncture but no scaffold implantation was made in the control group. MAIN OUTCOME MEASURES: Cell apoptosis was detected using TUNEL; Bax, Bcl-2, and Caspase-3 expressions were measured using the SABC method. RESULTS: At days 1, 3, 7, and 14 after scaffold implantation, a few apoptotic cells were observed in the brain tissues near the puncture site, with more apoptotic cells in the implantation group (P < 0.05). However, both groups showed similar apoptosis levels by day 30 after implantation. Implantation increased Bax, Bcl-2, and Caspase-3 expressions on days 3 and 7 after implantation (P < 0.05) but decreased the ratio of Bcl-2 to Bax in the implantation group was significantly lower on days 3 and 7 (P < 0.05), with no significant difference by day 30 after implantation (P > 0.05). CONCLUSION: The collagen-heparin sulfate scaffold has good biocompatibility to porcine brain tissues.