rada16-i and Brain-Injuries

Traumatic brain injury (TBI) and neurosurgical procedures commonly result in tissue loss within the cerebral parenchyma. Regeneration is limited by the anatomical tissue gaps and the hostile microenvironment created by the trauma. A search for novel biomaterials that are neuroprotective and conducive to healing and regeneration is needed. One approach is with the use of RADA16-I, a type I self-assembling peptide nanofiber scaffold. We review the current evidence on the use of RADA16-I and describe our experience with its use in rodent models of surgical brain injury. A cortical resection model is used to mimic the significant amount of tissue loss seen in TBI and clinical surgery. The use of RADA16-I as a carrier of transplantable neuroprogenitor cells and a potential topical hemostatic agent is described. RADA16-I can bridge tissue gaps and reduce surrounding reactive changes. Embedment of transplantable cells within the tissue scaffold is feasible. RADA16-I achieves hemostasis almost instantaneously and is associated with less tissue damage when compared with other conventional methods. There are, however, certain limitations with the application of RADA16-I mainly due to its intrinsically low pH and need for prebuffering. The use of peptide nanofiber scaffold is a promising approach for the reconstruction of the injured brain. New experimental models and research methods are required to fully explore its potential in minimizing secondary brain injuries and to promote neuronal regeneration.

Topics: Animals; Brain Injuries; Female; Immunohistochemistry; Magnetic Resonance Imaging; Nanofibers; Peptides; Rats; Rats, Sprague-Dawley

RADA16-I is a synthetic type I self-assembling peptide nanofiber scaffold (SAPNS) which may serve as a novel biocompatible hemostatic agent. Its application in neurosurgical hemostasis, however, has not been explored. Although RADA16-I is nontoxic and nonimmunogenic, its intrinsic acidity may potentially provoke inflammation in the surgically injured brain. We conducted an animal study to compare RADA16-I with fibrin sealant, a commonly used agent, with the hypothesis that the former would be a comparable alternative. Using a standardized surgical brain injury model, 30 Sprague-Dawley rats were randomized into three treatment groups: RADA16-I, fibrin sealant or gelatin sponge (control). Animals were sacrificed on day 3 and 42. Astrocytic and microglial infiltrations within the cerebral parenchyma adjacent to the operative site were significantly lower in the RADA16-I and fibrin sealant groups than control. RADA16-I did not cause more cellular inflammatory response despite its acidity when compared with fibrin sealant. Immunohistochemical studies showed infiltration by astrocytes and microglia into the fibrin sealant and RADA16-I grafts, suggesting their potential uses as tissue scaffolds. RADA16-I is a promising candidate for further translational and clinical studies that focus on its applications as a safe and effective hemostat, proregenerative nanofiber scaffold as well as drug and cell carrier.

Topics: Administration, Topical; Animals; Brain Injuries; Disease Models, Animal; Fibrin Tissue Adhesive; Hemostasis, Surgical; Hemostatics; Nanofibers; Neurosurgical Procedures; Peptides; Rats, Sprague-Dawley; Time Factors; Wound Healing