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Polyplex-Loaded Hydrogels for Local Gene Delivery to Human Dermal Fibroblasts.

Jose Antonio Duran-Mota1,2, Júlia Quintanas Yani1,2, Benjamin D Almquist2

  • 1Grup d'Enginyeria de Materials (GEMAT), Institut Químic de Sarrià, Universitat Ramon Llull, Via Augusta 390, Barcelona 08017, Spain.

ACS Biomaterials Science & Engineering
|June 3, 2021
PubMed
Summary
This summary is machine-generated.

This study presents a novel hydrogel wound dressing that delivers poly(β-amino ester) nanoparticles, offering sustained release for effective mRNA gene therapy. This innovation aims to improve chronic wound healing and reduce the need for amputation.

Keywords:
gene deliveryhuman dermal fibroblastshydrogelnanoparticlespoly(β-amino ester)spolyethylene glycolskinwound healing

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Area of Science:

  • Biomaterials Science
  • Regenerative Medicine
  • Gene Therapy

Background:

  • Chronic wounds affect 2-6% of the population, posing a significant healthcare burden.
  • Current treatments are often ineffective, leading to pain, distress, and amputation.
  • Gene therapy, particularly mRNA, shows promise but faces challenges in delivery and protection.

Purpose of the Study:

  • To develop an injectable, biodegradable hydrogel wound dressing for sustained delivery of nanoparticles.
  • To demonstrate the hydrogel's ability to protect mRNA and facilitate transfection into dermal fibroblasts.
  • To provide a novel platform for gene therapy in chronic wound treatment.

Main Methods:

  • Development of an injectable, biodegradable, and cytocompatible hydrogel.
  • Encapsulation and sustained release of poly(β-amino ester) (pBAE) nanoparticles within the hydrogel.
  • Assessment of mRNA protection and transfection efficiency in human dermal fibroblasts.

Main Results:

  • The hydrogel dressing successfully delivered pBAE nanoparticles in a sustained manner.
  • pBAE nanoparticles protected the mRNA cargo from degradation.
  • Sustained release from the hydrogel led to efficient transfection of human dermal fibroblasts.

Conclusions:

  • The developed hydrogel wound dressing is a promising platform for sustained mRNA gene therapy delivery.
  • This technology addresses key challenges in gene therapy for chronic wound healing.
  • The prototype has the potential to advance the treatment of chronic wounds and prevent limb amputation.