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Oxidation-Responsive, Tunable Growth Factor Delivery from Polyelectrolyte-Coated Implants.

John R Martin1,2, MayLin T Howard1,2, Sheryl Wang1,3

  • 1Koch Institute for Integrative Cancer Research, Massachusetts Institute of Technology, Cambridge, MA, 02139, USA.

Advanced Healthcare Materials
|March 19, 2021
PubMed
Summary
This summary is machine-generated.

New biodegradable coatings for tissue engineering scaffolds release therapeutic molecules in response to cell-generated signals. This controlled drug delivery enhances bone regeneration and offers tunable treatment for patients.

Keywords:
BMP-2boneslayer-by-layerreactive oxygen speciesresponsive drug delivery

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Polymer Chemistry

Background:

  • Polyelectrolyte multilayer (PEM) coatings assembled via layer-by-layer (LbL) technology are used in tissue engineering scaffolds for sustained therapeutic molecule release, aiding bone defect regeneration.
  • Current PEM systems often rely on non-specific hydrolysis for drug release, limiting adaptability to patient-specific needs.
  • A need exists for drug delivery systems that respond to local biological cues for more precise therapeutic intervention.

Purpose of the Study:

  • To synthesize a novel LbL-compatible polycation that degrades in response to cell-generated reactive oxygen species (ROS).
  • To develop tunable, ROS-responsive PEM coatings for controlled release of bone morphogenetic protein-2 (BMP-2) in bone tissue engineering.
  • To evaluate the efficacy of ROS-responsive coatings in promoting bone regeneration in a pre-clinical model.

Main Methods:

  • Synthesis of thioketal-based polycations designed for selective cleavage by ROS.
  • Fabrication of PEM films incorporating BMP-2 using LbL assembly with the synthesized polycations.
  • In vitro assessment of ROS-mediated BMP-2 release kinetics and tunability based on polyanion choice.
  • In vivo evaluation of PEM coating performance in critically-sized rat calvarial defects.

Main Results:

  • The synthesized thioketal-based polymers were effectively incorporated into PEM films and degraded by physiologic doses of ROS.
  • Tunable release of BMP-2 was achieved, with release rates influenced by the polyanions used in film construction.
  • In vivo studies showed a 50% increase in bone regeneration in rat calvarial defects with the most ROS-sensitive coatings.
  • ROS-responsive coatings extended the BMP-2 delivery half-life threefold compared to conventional hydrolytically-sensitive coatings.

Conclusions:

  • Environmentally-responsive PEM coatings offer a tunable drug delivery platform for regenerative medicine.
  • ROS-degradable polymers enable precise, stimulus-triggered therapeutic release, overcoming limitations of hydrolytic degradation.
  • These advanced coatings demonstrate significant potential for enhancing bone regeneration and clinical translation.