Functional biopolymer-based matrices for modulation of chronic wound enzyme activities

• Published in: Acta biomaterialia Vol. 9; no. 2; pp. 5216 - 5225
• Main Authors: Francesko, Antonio, Soares da Costa, Diana, Reis, Rui L., Pashkuleva, Iva, Tzanov, Tzanko
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.02.2013
• Subjects: Adsorption; Animals; Bandages; biocompatibility; biopolymers; Biopolymers - pharmacology; catechin; Cattle; Cell Line; Cell Shape - drug effects; Cell Survival - drug effects; cell viability; Chitosan; Chronic wounds; Collagen; Collagen - metabolism; collagenase; Collagenases - metabolism; Cross-Linking Reagents - pharmacology; Elastic Modulus - drug effects; enzyme activity; epigallocatechin; fibroblasts; Fibroblasts - cytology; Fibroblasts - drug effects; Fibroblasts - enzymology; Fibroblasts - ultrastructure; gallic acid; Humans; Hyaluronic acid; Hydrogen-Ion Concentration - drug effects; inflammation; Inhibitory Concentration 50; modulus of elasticity; molecular weight; myeloperoxidase; Peroxidase - antagonists & inhibitors; Peroxidase - metabolism; Polyphenols; Polyphenols - pharmacology; Porifera; Proteolysis - drug effects; Spectroscopy, Fourier Transform Infrared; Time Factors; Wound Healing - drug effects; Polyphenols; Chronic wounds; Chitosan; Hyaluronic acid; Collagen
• ISSN: 1742-7061; 1878-7568
• DOI: 10.1016/j.actbio.2012.10.014

Collagen, collagen/hyaluronic acid (HA) and collagen/HA/chitosan (CS) sponges loaded with epigallocatechin gallate (EGCG), catechin (CAT) and gallic acid (GA) were developed and evaluated as active chronic wound dressings. Their physico-mechanical properties, biostability, biocompatibility and ability to inhibit in vitro myeloperoxidase (MPO) and collagenase—major enzymes related with the persistent inflammation in chronic wounds—were investigated as a function of the biopolymer composition and the polyphenolic compound used. The results demonstrated that the molecular weight of HA influences significantly the bulk properties of the obtained materials: higher elastic modulus, swelling ability and biostability against collagenase were measured when HA with higher molecular weights (830 and 2000kDa) were added to the collagen matrices. The addition of CS and the polyphenols increased further the biostability of the sponges. Preliminary in vitro tests with fibroblasts revealed that the cells were able to adhere to all sponges. Cell viability was not affected significantly by the addition of the polyphenols; however, the presence of CS or high molecular weight HA in the sponge composition was associated with lower cellular viability. Finally, all specimens containing polyphenols efficiently inhibited the MPO activity. The highest inhibition capacity was observed for EGCG (IC50=15±1μM) and it was coupled to the highest extent of binding to the biopolymers (>80%) and optimal release profile from the sponges that allowed for prolonged (up to 3–5days) effects.