Zinc-Releasing Fibrous Scaffolds Modulate Fibroblast, Endothelial, and Macrophage Interactions for Vascularized...

Area of Science:

• Biomaterials Science
• Regenerative Medicine
• Tissue Engineering

Background:

• Fibrous scaffolds are crucial for tissue repair, but limitations like poor biodegradability and bioactivity hinder their use.
• Existing scaffolds often lack controlled therapeutic release, impacting their biomedical applications.

Purpose of the Study:

• To develop and evaluate electrospun poly(glycolic-co-lactic acid) (PLGA) fibrous scaffolds embedded with zinc nanoparticles (Zn NPs).
• To assess the physicochemical properties, biocompatibility, and therapeutic potential of these Zn NP-embedded scaffolds for tissue regeneration.

Main Methods:

• Fabrication of PLGA scaffolds with varying wt % of Zn NPs using electrospinning.
• Evaluation of physicochemical properties, including Zn2+ release kinetics.
• Assessment of bioactivity using human dermal fibroblasts (HDFn), human umbilical vein endothelial cells (HUVECs), and RAW264.7 macrophages in vitro.
• Indirect co-culture studies to analyze cell-cell interactions and angiogenic potential.

Main Results:

• The PLGA scaffold with 1.0 wt % Zn NPs (PLZ2) demonstrated controlled Zn2+ release, avoiding burst toxicity.
• PLZ2 scaffolds promoted fibroblast-to-myofibroblast differentiation and enhanced secretion of angiogenic growth factors (VEGF, bFGF).
• Zn2+ release stimulated HUVEC survival, migration, capillary-like network formation, and macrophage polarization towards M1/M2 phenotypes.

Conclusions:

• Zinc-releasing PLGA fibrous scaffolds show significant potential for promoting vascularized tissue regeneration.
• The controlled release of Zn2+ supports key cellular processes essential for wound healing and angiogenesis.
• This biomaterial strategy offers a promising approach for tissue engineering applications requiring enhanced vascularization.