Encapsulation of the growth factor neurotrophin-3 in heparinised poloxamer hydrogel stabilises bioactivity and provides sustained release

Biomater Adv. 2024 May:159:213837. doi: 10.1016/j.bioadv.2024.213837. Epub 2024 Mar 20.

Abstract

Poloxamer-based hydrogels show promise to stabilise and sustain the delivery of growth factors in tissue engineering applications, such as following spinal cord injury. Typically, growth factors such as neurotrophin-3 (NT-3) degrade rapidly in solution. Similarly, poloxamer hydrogels also degrade readily and are, therefore, only capable of sustaining the release of a payload over a small number of days. In this study, we focused on optimising a hydrogel formulation, incorporating both poloxamer 188 and 407, for the sustained delivery of bioactive NT-3. Hyaluronic acid blended into the hydrogels significantly reduced the degradation of the gel. We identified an optimal hydrogel composition consisting of 20 % w/w poloxamer 407, 5 % w/w poloxamer 188, 0.6 % w/w NaCl, and 1.5 % w/w hyaluronic acid. Heparin was chemically bound to the poloxamer chains to enhance interactions between the hydrogel and the growth factor. The unmodified and heparin-modified hydrogels exhibited sustained release of NT-3 for 28 days while preserving the bioactivity of NT-3. Moreover, these hydrogels demonstrated excellent cytocompatibility and had properties suitable for injection into the intrathecal space, underscoring their suitability as a growth factor delivery system. The findings presented here contribute valuable insights to the development of effective delivery strategies for therapeutic growth factors for tissue engineering approaches, including the treatment of spinal cord injury.

Keywords: Bioactivity assay; Controlled release; Drug delivery system; Growth factor; NT-3; Tissue engineering.

MeSH terms

  • Delayed-Action Preparations / chemistry
  • Delayed-Action Preparations / pharmacology
  • Delayed-Action Preparations / therapeutic use
  • Heparin / chemistry
  • Heparin / pharmacology
  • Humans
  • Hyaluronic Acid / chemistry
  • Hyaluronic Acid / therapeutic use
  • Hydrogels* / therapeutic use
  • Intercellular Signaling Peptides and Proteins / therapeutic use
  • Poloxamer / chemistry
  • Poloxamer / therapeutic use
  • Spinal Cord Injuries* / drug therapy

Substances

  • Hydrogels
  • Poloxamer
  • Delayed-Action Preparations
  • Hyaluronic Acid
  • Heparin
  • Intercellular Signaling Peptides and Proteins