Erythropoietin-PLGA-PEG as a local treatment to promote functional recovery and neurovascular regeneration after peripheral nerve injury

• Published in: Journal of nanobiotechnology 2022-10, Vol.20 (1), p.461-17, Article 461
• Main Authors: Manto, Kristen M, Govindappa, Prem Kumar, Martinazzi, Brandon, Han, Aijie, Hegarty, John P, Koroneos, Zachary, Talukder, M A Hassan, Elfar, John C
• Format: Article
• Language: English
• Subjects: Angiogenesis; Animals; Block copolymer; Block copolymers; Blood vessels; Body temperature; Care and treatment; Controlled release; Crush Injuries - drug therapy; Crush injury; Crushing; Delayed-Action Preparations - pharmacology; Drug delivery; Drug delivery systems; Erythropoietin; Erythropoietin - chemistry; Erythropoietin - pharmacology; Erythropoietin - therapeutic use; Fibers; Grip strength; Health aspects; Hydrogels; Injuries; Mice; Nerve Regeneration; Nervous system; Particle size; Patient outcomes; Peripheral nerve; Peripheral nerve diseases; Peripheral Nerve Injuries - drug therapy; Peripheral nerves; Physiochemistry; Polyethylene glycol; Polylactide-co-glycolide; Polymers; Recovery; Recovery of function; Regeneration; Sciatic nerve; Sciatic Neuropathy - drug therapy; Spectrum analysis; Thermogel
• ISSN: 1477-3155; 1477-3155
• DOI: 10.1186/s12951-022-01666-5

Traumatic peripheral nerve injury (TPNI) is a major medical problem with no universally accepted pharmacologic treatment. We hypothesized that encapsulation of pro-angiogenic erythropoietin (EPO) in amphiphilic PLGA-PEG block copolymers could serve as a local controlled-release drug delivery system to enhance neurovascular regeneration after nerve injury. In this study, we synthesized an EPO-PLGA-PEG block copolymer formulation. We characterized its physiochemical and release properties and examined its effects on functional recovery, neural regeneration, and blood vessel formation after sciatic nerve crush injury in mice. EPO-PLGA-PEG underwent solution-to-gel transition within the physiologically relevant temperature window and released stable EPO for up to 18 days. EPO-PLGA-PEG significantly enhanced sciatic function index (SFI), grip strength, and withdrawal reflex post-sciatic nerve crush injury. Furthermore, EPO-PLGA-PEG significantly increased blood vessel density, number of junctions, and myelinated nerve fibers after injury. This study provides promising preclinical evidence for using EPO-PLGA-PEG as a local controlled-release treatment to enhance functional outcomes and neurovascular regeneration in TPNI.