RADA16-I Hydrogel-Released CXCL12 Stably Promotes Stem Cell Migration

Introduction: CXCL12 (Stromal cell-derived factor 1α, SDF - 1α) plays an important role in the nervous system development and neural repair, and is gradiently expressed in the central nervous system, mediating proper neural progenitor cell (NPCs) migration and survival. Due to a relatively short half-life and restriction of the blood-brain barrier (BBB) in systemic bioactive factor delivery, the delivery of CXCL12 and other bioactive factors has become a great challenge in research and clinical application. Aims: In order to observe the change of concentration grade and release time of CXCL12we studied the dynamic CXCL12 prolonged release pattern with the injectable, nontoxic, modifiable and degradable RADA16-I peptide hydrogel. The hydrogel resulted in a relatively stable CXCL12 concentration and provided more suitable microenvironment for stem cell survival and migration in vitro. The following major experiments were conducted: 1. Anti-adhesion and neural protection with RADA16-I were performed in rabbit skull trauma model; 2. Fluorescent semi-quantitative CLSM was used for analysis of CXCL12 released from CXCL12 hydrogel mixture, and ELISA for detecting CXCL12 release kinetic curve was utilized; 3. Effective concentration was estimated through the peak concentration of CXCL12 load and was determined with trans-well migration assay. Results: 1. RADA16-I alone potentially played a role in anti-adhesion and neural repair. Furthermore, RADA16-I hydrogel slow-release system smoothly released chemokine CXCL12 in vitro. 2. Stable CXCL12 released system was more effective to be used for tissue repair compared to quickly declined CXCL12 without hydrogel system. 3. The peak concentration (50 ng/ml) of CXCL12 load released from hydrogel was the functional concentration for the induction of directional migration in mouse neuronal progenitor cells (mNPCs). Conclusions: Slow-released hydrogel system and mixture, RADA16-I and CXCL12, offered effective grade level for cell migration. This system is potentially beneficial for neural tissue protection and neural repair in clinic.