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Growth Factor Loaded Thermo-Responsive Injectable Hydrogel for Enhancing Diabetic Wound Healing

Background: Diabetic wound (DW) is the most devastating complication resulting in significant mortality and morbidity in diabetic patients. The objective of the current study was to formulate Epidermal Growth Factor loaded Chitosan nanoparticle impregnated with thermos-responsive injectable hydrogel...

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Autores principales: Tallapaneni, Vyshnavi, Mude, Lavanya, Pamu, Divya, Palanimuthu, Vasanth Raj, Magham, Sai Varshini, Karri, Veera Venkata Satyanarayana Reddy, Parvathaneni, Madhukiran
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9858321/
https://www.ncbi.nlm.nih.gov/pubmed/36661795
http://dx.doi.org/10.3390/gels9010027
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author Tallapaneni, Vyshnavi
Mude, Lavanya
Pamu, Divya
Palanimuthu, Vasanth Raj
Magham, Sai Varshini
Karri, Veera Venkata Satyanarayana Reddy
Parvathaneni, Madhukiran
author_facet Tallapaneni, Vyshnavi
Mude, Lavanya
Pamu, Divya
Palanimuthu, Vasanth Raj
Magham, Sai Varshini
Karri, Veera Venkata Satyanarayana Reddy
Parvathaneni, Madhukiran
author_sort Tallapaneni, Vyshnavi
collection PubMed
description Background: Diabetic wound (DW) is the most devastating complication resulting in significant mortality and morbidity in diabetic patients. The objective of the current study was to formulate Epidermal Growth Factor loaded Chitosan nanoparticle impregnated with thermos-responsive injectable hydrogel with protease inhibitor. EGF, shown in all stages of wound healing from inflammation to proliferation and remodelling, combined with Doxycycline, a well-known anti-inflammatory and anti-bacterial drug, could be a better strategy in diabetic wound healing. However, EGF’s low stability makes it difficult to use. Methodology: The nanoparticles were prepared using the ionic gelation method. The prepared nanoparticles were evaluated for particle size, zeta potential, entrapment efficiency, and SEM studies. Further, the optimized nanoparticle batch was loaded into hydrogel with a protease inhibitor. The hydrogel was evaluated for morphology, protease degradation, in vitro drug release, anti-bacterial activity, cell migration, in vitro cell biocompatibility, and in vivo wound healing studies. Results and Conclusion: The particle size analysis of nanoparticles revealed the size (203 ± 1.236 nm), Zeta potential (+28.5 ± 1.0 mV), and entrapment efficiency of 83.430 ± 1.8%, respectively. The hydrogel showed good porous morphology, injectability, thermo-responsive, biocompatibility, and controlled drug release. In vitro anti-bacterial studies revealed the potential anti-bacterial activity of doxycycline against various microbes. In vivo data indicated that combining EGF and DOX considerably reduced inflammation time-dependent than single-agent treatment. Furthermore, histological studies corroborated these findings. After topical application of hydrogel, histopathology studies revealed significant collagen synthesis and a fully regenerated epithelial layer and advancement in all three stages (proliferation, remodelling, and maturation), which are required to improve the diabetic wound healing process by any dressing. These findings demonstrated that hydrogel promoted cutaneous wound healing in STZ-induced rats by suppressing inflammation at the wound site. Furthermore, histological studies corroborated these findings. After topical application of hydrogel, histopathology studies revealed significant collagen synthesis, a fully regenerated epithelial layer, and advancement in all three stages (proliferation, remodelling, and maturation), which are required to improve the diabetic wound healing process by any dressing. These findings demonstrated that hydrogel promoted cutaneous wound healing in STZ-induced rats by suppressing inflammation at the wound site.
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spelling pubmed-98583212023-01-21 Growth Factor Loaded Thermo-Responsive Injectable Hydrogel for Enhancing Diabetic Wound Healing Tallapaneni, Vyshnavi Mude, Lavanya Pamu, Divya Palanimuthu, Vasanth Raj Magham, Sai Varshini Karri, Veera Venkata Satyanarayana Reddy Parvathaneni, Madhukiran Gels Article Background: Diabetic wound (DW) is the most devastating complication resulting in significant mortality and morbidity in diabetic patients. The objective of the current study was to formulate Epidermal Growth Factor loaded Chitosan nanoparticle impregnated with thermos-responsive injectable hydrogel with protease inhibitor. EGF, shown in all stages of wound healing from inflammation to proliferation and remodelling, combined with Doxycycline, a well-known anti-inflammatory and anti-bacterial drug, could be a better strategy in diabetic wound healing. However, EGF’s low stability makes it difficult to use. Methodology: The nanoparticles were prepared using the ionic gelation method. The prepared nanoparticles were evaluated for particle size, zeta potential, entrapment efficiency, and SEM studies. Further, the optimized nanoparticle batch was loaded into hydrogel with a protease inhibitor. The hydrogel was evaluated for morphology, protease degradation, in vitro drug release, anti-bacterial activity, cell migration, in vitro cell biocompatibility, and in vivo wound healing studies. Results and Conclusion: The particle size analysis of nanoparticles revealed the size (203 ± 1.236 nm), Zeta potential (+28.5 ± 1.0 mV), and entrapment efficiency of 83.430 ± 1.8%, respectively. The hydrogel showed good porous morphology, injectability, thermo-responsive, biocompatibility, and controlled drug release. In vitro anti-bacterial studies revealed the potential anti-bacterial activity of doxycycline against various microbes. In vivo data indicated that combining EGF and DOX considerably reduced inflammation time-dependent than single-agent treatment. Furthermore, histological studies corroborated these findings. After topical application of hydrogel, histopathology studies revealed significant collagen synthesis and a fully regenerated epithelial layer and advancement in all three stages (proliferation, remodelling, and maturation), which are required to improve the diabetic wound healing process by any dressing. These findings demonstrated that hydrogel promoted cutaneous wound healing in STZ-induced rats by suppressing inflammation at the wound site. Furthermore, histological studies corroborated these findings. After topical application of hydrogel, histopathology studies revealed significant collagen synthesis, a fully regenerated epithelial layer, and advancement in all three stages (proliferation, remodelling, and maturation), which are required to improve the diabetic wound healing process by any dressing. These findings demonstrated that hydrogel promoted cutaneous wound healing in STZ-induced rats by suppressing inflammation at the wound site. MDPI 2022-12-29 /pmc/articles/PMC9858321/ /pubmed/36661795 http://dx.doi.org/10.3390/gels9010027 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Tallapaneni, Vyshnavi
Mude, Lavanya
Pamu, Divya
Palanimuthu, Vasanth Raj
Magham, Sai Varshini
Karri, Veera Venkata Satyanarayana Reddy
Parvathaneni, Madhukiran
Growth Factor Loaded Thermo-Responsive Injectable Hydrogel for Enhancing Diabetic Wound Healing
title Growth Factor Loaded Thermo-Responsive Injectable Hydrogel for Enhancing Diabetic Wound Healing
title_full Growth Factor Loaded Thermo-Responsive Injectable Hydrogel for Enhancing Diabetic Wound Healing
title_fullStr Growth Factor Loaded Thermo-Responsive Injectable Hydrogel for Enhancing Diabetic Wound Healing
title_full_unstemmed Growth Factor Loaded Thermo-Responsive Injectable Hydrogel for Enhancing Diabetic Wound Healing
title_short Growth Factor Loaded Thermo-Responsive Injectable Hydrogel for Enhancing Diabetic Wound Healing
title_sort growth factor loaded thermo-responsive injectable hydrogel for enhancing diabetic wound healing
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9858321/
https://www.ncbi.nlm.nih.gov/pubmed/36661795
http://dx.doi.org/10.3390/gels9010027
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