Targeted Delivery of Microneurotrophin BNN27 via Biomaterial Grafts Protects Retinal Ganglion Cells After Optic Nerve Injury

J Biomed Mater Res B Appl Biomater. 2026 Jan;114(1):e70013. doi: 10.1002/jbmb.70013.

Abstract

Emerging neurotrophin treatments for optic nerve injury (ONI) aim to prevent the loss of retinal ganglion cells (RGCs) and enhance axonal regeneration. Microneurotrophins (MNTs), small-molecule mimetics of neurotrophins, have shown neuroprotective effects in various animal models of neurodegeneration, yet MNT effects on ONI remain unknown. Here, we study the effects of BNN27, a MNT that mimics NGF, in a mouse model of optic nerve crush (ONC) and compare the targeted administration via biomaterial grafts placed around the ONC lesion against standard eye drop delivery. Compared to eye drop delivery, targeted biomaterial-based BNN27 delivery resulted in more consistent and efficient RGC neuroprotection and reduced microglia-mediated inflammation in the ONC lesion. Our findings demonstrate that targeted delivery of MNTs can alleviate key consequences of ONI and, therefore, be an essential part of effective combinatorial ONI treatments.

Keywords: biomaterial grafts; microneurotrophins; neuroprotection; optic nerve injury; targeted delivery.

MeSH terms

  • Animals
  • Biocompatible Materials* / chemistry
  • Biocompatible Materials* / pharmacology
  • Disease Models, Animal
  • Drug Delivery Systems
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Growth Factors* / chemistry
  • Nerve Growth Factors* / pharmacology
  • Neuroprotective Agents* / chemistry
  • Neuroprotective Agents* / pharmacology
  • Optic Nerve Injuries* / drug therapy
  • Optic Nerve Injuries* / metabolism
  • Optic Nerve Injuries* / pathology
  • Retinal Ganglion Cells* / drug effects
  • Retinal Ganglion Cells* / metabolism
  • Retinal Ganglion Cells* / pathology

Substances

  • Neuroprotective Agents
  • Biocompatible Materials
  • Nerve Growth Factors