Neuroregenerative and neuroprotective effects of bioengineered scaffolds in spinal cord injury: a systematic review of preclinical and early phase clinical studies

Systematic Review To systematically examine the use of bioengineered scaffolds, with/without bioactive agents, drugs, or cellular transplants in preclinical animal models and human studies of spinal cord injury (SCI). Sina Trauma and Surgery Research Center, Tehran University of Medical Sciences A systematic review and meta-analysis was conducted following PRISMA guidelines and registered in PROSPERO (ID: CRD42023437266). A comprehensive search in MEDLINE and Embase on 8/27/2023 identified studies on scaffolds as neuroregenerative and neuroprotective treatments for SCI. Human studies were assessed using ROBINS-I, and meta-analysis focused on clinical outcomes. Of 4561 articles screened, 931 studies were included: in-vivo (82%), in-vitro (16%), and human studies (1%). Various biomaterials (N = 82; natural: 38%; synthetic: 62%), cell types (N = 27; NSCs: 24%, Schwann cells: 13%, NPCs: 12%), bioactive agents (N = 38; NT-3: 32%, BDNF: 25%, FGF: 24%), and pharmacological agents (N = 88; chABC: 12%, heparin: 11%, taxels: 10%) were analyzed. Fourteen human studies included acute and chronic SCI patients, with cervical (36%) and thoracic SCI (64%). Clinical trials demonstrated moderate to low quality (ROBINS-I). Our meta-analysis indicated that the pooled 2-scale AIS conversion rate was 30.59% (p = 0.005) ranging from 33.46% (p = 0.036) in acute to 28.35% (p = 0.084) in chronic SCI. Furthermore, the pooled 1-scale AIS conversion rate was 11.79% (p = 0.011), spanning from 17.31% (p = 0.131) in acute to 7.44% (p = 0.081) in chronic SCI. Scaffold implantation shows promising neuroregenerative potential, evidenced by AIS grade improvement in human studies. Scaffolds are advancing rapidly from laboratory research to clinical trials, expanding treatment options for SCI.