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. 2021 Jun;10(6):301-316.
doi: 10.1089/wound.2020.1206. Epub 2020 Aug 7.

Polymeric Composite Dressings Containing Calcium-Releasing Nanoparticles Accelerate Wound Healing in Diabetic Mice

Soledad Perez-Amodio  1   2   3 , Nuria Rubio  1   4 , Olaia F Vila  1   4 , Claudia Navarro-Requena  1   2 , Oscar Castaño  1   2   5   6 , Aitor Sanchez-Ferrero  1   2 , Joan Marti-Munoz  1   2 , Mercè Alsina-Giber  7 , Jeronimo Blanco  1   4 , Elisabeth Engel  1   2   3
Affiliations

Polymeric Composite Dressings Containing Calcium-Releasing Nanoparticles Accelerate Wound Healing in Diabetic Mice

Soledad Perez-Amodio et al. Adv Wound Care (New Rochelle). 2021 Jun.

Abstract

Objective: Wound healing is a complex process that involves the interaction between different cell types and bioactive factors. Impaired wound healing is characterized by a loss in synchronization of these interactions, resulting in nonhealing chronic wounds. Chronic wounds are a socioeconomic burden, one of the most prominent clinical manifestations of diabetes, however, they lack satisfactory treatment options. The objective of this study was to develop polymeric composites that deliver ions having wound healing properties and evaluate its performance using a pressure ulcer model in diabetic mice. Approach: To develop a polymeric composite wound dressing containing ion-releasing nanoparticles for chronic wound healing. This composite was chemically and physically characterized and evaluated using a pressure ulcer wound model in diabetic (db/db) mice to explore their potential as novel wound dressing. Results: This dressing exhibits a controlled ion release and a good in vitro bioactivity. The polymeric composite dressing treatment stimulates angiogenesis, collagen synthesis, granulation tissue formation, and accelerates wound closure of ischemic wounds created in diabetic mice. In addition, the performance of the newly designed composite is remarkably better than a commercially available dressing frequently used for the treatment of low-exuding chronic wounds. Innovation: The developed nanoplatforms are cell- and growth factor free and control the host microenvironment resulting in enhanced wound healing. These nanoplatforms are available by cost-effective synthesis with a defined composition, offering an additional advantage in potential clinical application. Conclusion: Based on the obtained results, these polymeric composites offer an optimum approach for chronic wound healing without adding cells or external biological factors.

Keywords: angiogenesis; bioactive dressings; chronic wounds; diabetes.

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Conflict of interest statement

No competing financial interests exist. The content of this article was expressly written by the authors listed. No ghostwriters were used to write this article.

Figures

None
Elisabeth Engel, PhD
Figure 1.
Figure 1.
Schematic representation of the workflow. (A) Fabrication of PLA-SG5 mats by electrospinning. (B) Morphological characterization of PLA-SG5 mats by CLMS, FE-SEM, contact angle, and ion release. (C) Biocompatibility of PLA-SG5 using human dermal fibroblasts. (D) In vivo evaluation of PLA-SG5 mats using a pressure ulcer model in diabetic mice. CLMS, confocal laser microscopy scanner; FE-SEM, field emission scanning electron microscopy; PLA, poly(lactic acid). Color images are available online.
Figure 2.
Figure 2.
Characterization of electrospun PLA mats with and without SG5 particles. (A, B) PLA (left) and PLA-SG5 (right) mats imaged with SEM. Arrowheads indicate the presence of particles embedded in the fibers. (C) Representative tensile–stress curves of mats. (D) Cumulative calcium release over time of mats in CCM. (n = 5, mean ± SD). CCM, complete culture medium; SD, standard deviation. Color images are available online.
Figure 3.
Figure 3.
Three-dimensional reconstructions from CLSM sections of (A) PLA and (B) PLA-SG5 mats. Pore size distribution of PLA mats of pore areas (C) 0–425 μm2, (c) 0–105 μm2, and PLA-SG5 mats of pore area (D) 0–475 μm2, (d) 0–95 μm2. CLSM, confocal laser scanning microscopy. Color images are available online.
Figure 4.
Figure 4.
Assessment of human dermal fibroblasts viability in conditioned medium. (A) Adult human dermal fibroblast from healthy donors were exposed to CCM previously incubated with PLA or PLA-SG5 mats, and metabolic activity was quantified after 1 and 4 days posttreatment. Values were normalized to the average of the control sample exposed to nonconditioned medium on day 1. (n = 8, mean ± SD). Assessment of wound healing size at different time points. (B) Representative images of the group treated with Mepilex®, PLA, and PLA-SG5 on day 0, 3, and 8 posttreatment. (C) Percentage of wound size relative to the initial size during the course of the experiment. Data are expressed as the mean ± SD (n = 8). *p < 0.05 (vs. PLA-SG5), **p < 0.01 (vs. PLA-SG5), ****p < 0.0001 (vs. PLA-SG5). Scale bar = 0.5 mm. Color images are available online.
Figure 5.
Figure 5.
Analysis of wound structure from sections stained with H&E. (A) Representative images of wound sections stained with H&E from day 3 and 8 posttreatment. Arrows delimit the unepithelialized surface of the wound. (B) Quantification of the epithelial gap length from each experimental condition on day 3 and 8 posttreatment. Data are expressed as the mean ± SD of at least five wounds from different animals. *p < 0.05, **p < 0.01 (vs. PLA-SG5). ***p < 0.001 (vs. PLA-SG5). Scale bar = 1 mm. Color images are available online.
Figure 6.
Figure 6.
Analysis of granulation tissue and collagen deposition from sections stained with (A) H&E and (B) Masson's Trichrome. Representative images of all conditions from wound sections stained with H&E from day 3 and 8 posttreatment at two different magnifications showing the granulation tissue. (C) Increased collagen deposition in PLA-SG5 treated wounds at 3 and 8 days postwounding. *p < 0.05 (vs. PLA-SG5), ***p < 0.001 (vs. PLA-SG5). Scale bar = 250 μm. Color images are available online.
Figure 7.
Figure 7.
Imaging and quantification of blood vessels immunolabeled for CD31. (A) Representative images of immunostaining against CD31 of sections of wounds treated with Mepilex (Control), PLA, and PLA-SG5 mats at 3 and 8 days postwounding. (B) Quantification of the number of vessels from the immunostained images. *p < 0.05 (vs. PLA-SG5). ****p < 0.0001 (vs. PLA-SG5). Scale bar = 250 μm. Color images are available online.
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