Calcium (Ca²⁺) regulation assumes a critical role in the repair course of peripheral nerve injury (PNI). However, effective calcium sources capable of providing sustained Ca²⁺ signals to promote growth cone extension remain limited. Herein, the coupling of biotinylated dextran amine (BDA) to amine-functionalized hydroxyapatite nanorods (nHAP-NH₂) remarkably promoted and maintained the extension of growth cones throughout nerve regeneration. Therefore, a newly developed therapeutic system for PNI was constructed based on a hydrogel (Gel) loaded with BDA-nHAP (nHAP-NH₂ with surface modification of BDA) and vascular endothelial growth factor (VEGF). The sustained-release BDA-nHAP has the potential to continuously and targetedly increase the Ca²⁺ levels within the growth cone, and further boost neurite outgrowth by modulating the PI3K-PAK and MAPK signalling pathways. Moreover, VEGF can significantly promote angiogenesis in the early stage of nerve repair, which is critical for optimizing the functional efficacy of BDA-nHAP in enhancing neurogenesis. Thus, this innovative integrated therapeutic system with neurogenesis and angiogenesis capabilities may offer a new solution for achieving high-quality functional recovery from PNI. STATEMENT OF SIGNIFICANCE: For PNI, there remains a scarcity of effective calcium sources capable of providing sustained Ca²⁺ signals within the growth cone to enhance its extension. Herein, a newly developed therapeutic system for PNI was constructed based on a Gel loaded with BDA-nHAP and VEGF. The sustained-release BDA-nHAP has the potential to continuously and targetedly increase the Ca²⁺ levels within the growth cone, and further boost neurite outgrowth throughout the whole process of nerve regeneration. Moreover, VEGF can significantly promote angiogenesis in the early stage of nerve repair, which is critical for optimizing the functional efficacy of BDA-nHAP in enhancing neurogenesis. Thus, this innovative therapeutic system may offer a new solution for achieving high-quality functional recovery from PNI.

Physical injuries and neurodegenerative diseases often lead to irreversible damage to the organizational structure of the central nervous system (CNS) and peripheral nervous system (PNS), culminating in physiological malfunctions. Investigating these complex and diverse biological processes at the macro and micro levels will help to identify the cellular and molecular mechanisms associated with nerve degeneration and regeneration, thereby providing new options for the development of new therapeutic strategies for the functional recovery of the nervous system. Due to their distinct advantages, modern microfluidic platforms have significant potential for high-throughput cell and organoid cultures in vitro, the synthesis of a variety of tissue engineering scaffolds and drug carriers, and observing the delivery of drugs at the desired speed to the desired location in real time. In this review, we first introduce the types of nerve damage and the repair mechanisms of the CNS and PNS; then, we summarize the development of microfluidic platforms and their application in drug carriers. We also describe a variety of damage models, tissue engineering scaffolds, and drug carriers for nerve injury repair based on the application of microfluidic platforms. Finally, we discuss remaining challenges and future perspectives with regard to the promotion of nerve injury repair based on engineered microfluidic platform technology.

Ischemic stroke (IS) is a leading cause of death in the world, and there is still a lack of effective treatments. Ginkgolide B (GB) can antagonize the platelet activating factor receptor and has shown a significant curative effect on cerebral ischemia. However, GB and other drugs for IS have shown poor clinical efficacy due to their inability to cross the blood–brain barrier (BBB). Herein, red fluorescent carbonized polymer dots (CPDs) were developed as biocompatible nanocarriers to deliver GB to the brain tissue. Both in vivo and in vitro experiments verified the ability of GB-CPDs to penetrate the BBB, and GB-CPDs remained in the brain significantly longer than unmodified CPDs. In a rat model of middle cerebral artery occlusion (MCAO), circulatory administration of GB-CPDs effectively reduced cerebral infarct size and neuronal apoptosis, with a significantly better therapeutic effect compared to GB. This study provided a novel GB-based nanodrug that could target the brain with improved efficacy, showing great application potential in central nervous system diseases.