In Vitro Enhanced Performance of Human Platelet Lysate Gel Integrated with Mesoporous Silica Nanoparticle/Carboxymethyl Chitosan Composite Hydrogel: Structural Stability and Biological Activities for Chronic Wound Healing

TL;DR

A new hydrogel combining human platelet lysate with a composite material improves wound healing by enhancing structural stability and cell activity.

Contribution

A novel composite hydrogel was developed to improve structural integrity and growth factor retention for chronic wound healing.

Findings

The xPMC/hPLG hydrogel showed increased fibrin fiber density and structural stability compared to hPLG alone.

The composite hydrogel released growth factors like PDGF-BB and TGF-β1 in a controlled manner.

xPMC/hPLG enhanced fibroblast recruitment and proliferation, likely mediated by PDGF-BB.

Abstract

Treatment of chronic wounds is challenging due to a variety
of
interconnected intrinsic (patient-related) and extrinsic (external/local)
factors that disrupt the normal, orderly process of wound repair.
Although human platelet lysate (hPL)-based treatment offers a cost-effective
option for chronic wound diseases, the inherent limitations of hPL
gel (hPLG), particularly its diminished structural integrity and limited
retention of growth factors (GFs), hinder its utility for treating
chronic wounds. Therefore, a novel cross-linked plasma-treated mesoporous
silica nanoparticle/carboxymethyl chitosan composite (xPMC)-embedded
hPLG hydrogel (xPMC/hPLG), designed to prolong fibrin integrity and
enhance local retention of bioactive factors, was developed, characterized,
and assessed for fibrin structural integrity and biological performance,
including cellular chemotaxis and proliferation. Microcomputed tomography
(micro-CT) and scanning electron microscopy (SEM) analyses demonstrated
that xPMC possessed high porosity and interconnectivity, with evenly
distributed fibrin within the pores of the composite hydrogel. Compared
with hPLG alone, finer fibrin fibers with increased density were observed
in xPMC/hPLG. The observed interpenetrating network structure of xPMC/hPLG
was associated with the significantly reduced in vitro degradation
of the composite hydrogel. Moreover, it exhibited controlled local
release of the total protein and key growth factors, i.e., platelet-derived
growth factor-BB (PDGF-BB) and transforming growth factor-β1
(TGF-β1). Importantly, xPMC/hPLG more effectively enhanced the
recruitment and proliferation of periodontal fibroblasts than hPLG.
This superior induction of fibroblast recruitment was at least partly
mediated by PDGF-BB. In conclusion, the developed xPMC/hPLG composite
hydrogel demonstrated prolonged structural integrity, extended release
of bioactive GFs, and enhanced cell migration and proliferation. Future
in vivo studies will further validate this composite hydrogel for
enhancing the success of chronic wound treatment.

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