Heparin-Loaded Alginate Hydrogels: Characterization and Molecular Mechanisms of Their Angiogenic and Anti-Microbial Potential

Abstract

Background: Chronic wounds continue to be a global concern that demands substantial resources from the healthcare system. The process of cutaneous wound healing is complex, involving inflammation, blood clotting, angiogenesis, migration and remodeling. In the present study, commercially available alginate wound dressings were loaded with heparin. The purpose of the study was to enhance the angiogenic potential of alginate wound dressings and analyze the antibacterial activity, biocompatibility and other relevant properties. We also aimed to conduct some molecular and gene expression studies to elaborate on the mechanisms through which heparin induces angiogenesis. Methods: The physical properties of the hydrogels were evaluated by Fourier transform infrared spectroscopy (FTIR). Swelling ability was measured by soaking hydrogels in the Phosphate buffer at 37 °C, and cell studies were conducted to evaluate the cytotoxicity and biocompatibility of hydrogels in NIH3T3 (fibroblasts). Real-time PCR was conducted to check the molecular mechanisms of heparin/alginate-induced angiogenesis. The physical properties of the hydrogels were evaluated by Fourier transform infrared spectroscopy (FTIR). Results: FTIR confirmed the formation of heparin-loaded alginate wound dressing and the compatibility of both heparin and alginate. Among all, 10 µg/mL concentration of heparin showed the best antibacterial activity against E. coli. The swelling was considerably increased up to 1500% within 1 h. Alamar Blue assay revealed no cytotoxic effect on NIH3T3. Heparin showed good anti-microbial properties and inhibited the growth of E. coli in zones with a diameter of 18 mm. The expression analysis suggested that heparin probably exerts its pro-angiogenetic effect through VEGF and cPGE. Conclusions: We report that heparin-loaded alginate dressings are not cytotoxic and offer increased angiogenic and anti-bacterial potential. The angiogenesis is apparently taken through the VEGF pathway.

Alginate-Based Hydrogels and Scaffolds for Biomedical Applications

“…The best results were obtained against L. monocytogenes , P. aeruginosa , S. typhimurium and S. aureus . Although alginate does not have antimicrobial activity, alginate hydrogel retained and immobilized bacteria, allowing for a reaction of the active substance with the bacteria [ 85 ]. To investigate the angiogenic potential and antibacterial activity of heparin, three different concentrations (1, 5 and 10 µg/mL, marked A, B and C, respectively) were loaded into commercially available alginate wound dressing biomaterials [ 85 ].…”

“…Although alginate does not have antimicrobial activity, alginate hydrogel retained and immobilized bacteria, allowing for a reaction of the active substance with the bacteria [ 85 ]. To investigate the angiogenic potential and antibacterial activity of heparin, three different concentrations (1, 5 and 10 µg/mL, marked A, B and C, respectively) were loaded into commercially available alginate wound dressing biomaterials [ 85 ]. The loaded hydrogel samples displayed a much higher swelling rate (1524, 1202 and 1279% for samples A, B and C, respectively), compared to the non-loaded alginate sample (838%).…”

Diversity of Rationally Modified Polysaccharides for Pharmaceutical Applications

“…The exemplary antimicrobial, mucoadhesive, biocompatible, biodegradable, and nontoxic properties make it a potent polymer in food industry, drug delivery, tissue regeneration cosmetics, and wound dressings. To improve the physiochemical property, primary amino and hydroxyl groups [55][56][57] Created with BioRender.com. (Abbreviations: BMP2: bone morphogenetic protein 2; OCN: osteocalcin; TNF-α-tumor necrosis factor alpha; IL-1β: Interleukin 1 beta; #:downregulation;": upregulation).…”

“…Figure 4. Biomedical applications and molecular pathways regulated by modified alginate demonstrating apoptosis and anti proliferation of tumor cells in vitro [55][56][57]. Created with BioRender.com.…”

Surface engineered mesoporous silica carriers for the controlled delivery of anticancer drug 5-fluorouracil: Computational approach for the drug-carrier interactions using density functional theory

“…The main aim of designing a drug carrier system is to address the limitations related to drug delivery to the desired sites of therapeutic action while minimizing the adverse side effects and managing the therapeutics with great selectivity and control of the targeted sites ( Davis et al, 2008 ; Cal et al, 2014 ). For this purpose, so far, many materials, e.g., polymers, ceramics, bioactive glasses, organic–inorganic materials, proteins, and lipids, have been reported ( Vallet-Regí, 2006 ; Iqbal et al, 2019 ; Khan et al, 2019 ; Tayyab et al, 2019 ; Malik et al, 2020 ; Pasha et al, 2020 ; Fuloria et al, 2022 ; Karthic et al, 2022 ; Nawaz et al, 2022 ; Thalluri et al, 2022 ).…”