Spatiotemporal delivery of bioactive molecules for wound healing using stimuli-responsive biomaterials

Adv Drug Deliv Rev. 2020;161-162:22-41. doi: 10.1016/j.addr.2020.07.021. Epub 2020 Aug 1.


Wound repair is a fascinatingly complex process, with overlapping events in both space and time needed to pave a pathway to successful healing. This additional complexity presents challenges when developing methods for the controlled delivery of therapeutics for wound repair and tissue engineering. Unlike more traditional applications, where biomaterial-based depots increase drug solubility and stability in vivo, enhance circulation times, and improve retention in the target tissue, when aiming to modulate wound healing, there is a desire to enable localised, spatiotemporal control of multiple therapeutics. Furthermore, many therapeutics of interest in the context of wound repair are sensitive biologics (e.g. growth factors), which present unique challenges when designing biomaterial-based delivery systems. Here, we review the diverse approaches taken by the biomaterials community for creating stimuli-responsive materials that are beginning to enable spatiotemporal control over the delivery of therapeutics for applications in tissue engineering and regenerative medicine.

Keywords: Biomaterials; Controlled release; Drug delivery; Regenerative medicine; Tissue engineering.

Publication types

  • Research Support, Non-U.S. Gov't
  • Systematic Review

MeSH terms

  • Biocompatible Materials / administration & dosage*
  • Delayed-Action Preparations
  • Drug Delivery Systems / methods*
  • Electromagnetic Phenomena
  • Enzymes / metabolism
  • Humans
  • Hydrogels / chemistry
  • Hydrogen-Ion Concentration
  • Intercellular Signaling Peptides and Proteins / administration & dosage*
  • Nanoparticles / chemistry
  • Oligonucleotides / metabolism
  • Regeneration / physiology*
  • Regenerative Medicine
  • Ultrasonography
  • Wound Healing / drug effects*


  • Biocompatible Materials
  • Delayed-Action Preparations
  • Enzymes
  • Hydrogels
  • Intercellular Signaling Peptides and Proteins
  • Oligonucleotides