Multifunctional, Adhesive, and PDA-Coated Bioactive Glass Reinforced Composite Hydrogel for Regenerative Wound Healing

Abstract

Effective wound management imposes several challenges in clinical outcomes due to the complexity of the wound microenvironment, bacterial infections, impaired angiogenesis, aggravated inflammation, and enduring pain. In addition, adhesion on wet biological tissue is another extremely challenging task. Addressing all the issues is necessary for an effective wound healing process. Herein, we developed a unique multifunctional, adhesive composite hydrogel composed of gelatin, chitosan, polydopamine-coated bioactive glass (BG), and curcumin-capped silver nanoparticles (Cur-AgNPs) to target the multifaceted complexity of the wound. The PDA-coated BG serves multiple purposes: (1) adhesivity: catechol groups of PDA and Ca ion released from BG chelate the group present in the hydrogel network and surrounding tissues, (2) angiogenesis: promotes vascularization due to the release of Si from BG, and (3) BG also serves as the “reservoir” for the pain-relieving diclofenac sodium drug with a sustained-release behavior. Cur-AgNPs provide excellent bactericidal and anti-inflammatory properties to the composite hydrogel. In situ application of the composite hydrogel could serve the purpose of a “skin biomimetic” and work as a barrier along with bactericidal properties to inhibit the microbial growth. The multifunctional composite hydrogel (MCH) targeted multiple aspects of wound repair including pain alleviation, elimination of microbes (up to 99%), reduced inflammation, high adhesivity, and increased angiogenesis for effective skin regeneration. The MCH showed excellent wound healing potential as significant wound closure was observed at day 7 and also significantly upregulated the expression of crucial genes involved in the skin regeneration process along with increasing vascularization in the wound area.

Opportunities for Bioactive Glass in Gastrointestinal Conditions: A Review of Production Methodologies, Morphology, Composition, and Performance

“…The Stöber methodology enables manipulation of particle shape and morphology using catalysts. The precursors or ions usually incorporated during the hydrolysis and condensation reactions differentiate between silica-only nanoparticles and sol–gel BGs, with NH 4 OH playing a key role as a solvent. ,, However, adding organic compounds and metal ions affects hydrolysis–condensation reactions, resulting in undesirable morphological changes. , Careful control of experimental conditions is needed (e.g., TEOS/water ratio, reaction pH, precursor types, and concentration) to avoid agglomeration and ensure shape, size, regularity and homogeneity is retained as this directly impacts morphology and bioactivity. ,,, Individual, homogeneous, mesoporous Si-based particles of controllable size form under basic conditions. , Under acidic conditions, Si-based particles aggregate and form a 3D-gelled structure as condensation reactions proceed. , Surfactants or polymers are commonly used as templating agents, usually during the hydrolysis and condensation steps, to positively manipulate the morphological characteristics of sol–gel-derived BG morphology. ,,− For example, the surfactant cetyltrimethylammonium bromide (CTAB) enhances mesoporosity, surface area, pore volume, and particle shape of BG formulations during micelle-BG formation (discussed further in section ). ,,,,− However, CTAB and metal ions are cationic and interact with each other, decreasing mesoporosity and/or pore volume. ,, These challenges motivated investigation of additive manufacturing style synthesis techniques, although they are not commonly utilized.…”

“…When optimizing morphology in BG synthesis, polymers/surfactants are deployed as structure-directing agents, which self-assemble into micelles and create an ordered organic–inorganic mesophase. ,, Common MBG synthesis techniques utilize polymer templating (e.g., modified Stöber, microemulsion or electrospinning methodologies). ,,,,,, Early sol–gel synthesis methods discovered that high-temperature treatment of sol–gel BGs resulted in decreased or lost porosity . However, sol–gel BG calcination is necessary to incorporate metallic ions into the silica network, remove surfactants/polymers and to create well-ordered, mesoporous morphology. ,,, Many different surfactants/polymers are used: Pluronic P123, F127, CTAB are most common. ,,,,,,,− Porosity and pore structure can be tailored by altering different experimental parameters such as polymer concentration, pH, temperature, and mixing conditions. , One strategy to increase mesoporosity in a formulation utilizing CTAB was to use ethyl ether as a cosolvent.…”

“…The second approach to administering BG to skin wounds involved formulating them into fibers, scaffolds, and composite materials. ,,− ,,− ,,,− Due to their physical characteristics, manipulation of melt-derived BGs presented challenges in the translation to soft tissue applications. Morphologically tailored porous sol–gel BGs provide a means to overcome these challenges.…”

“…1,44,48 Hence, mesoporous BGN can be used to codeliver biologically active ions and therapeutics, provided morphological characteristics are appropriately optimized. 38,44,48 When optimizing morphology in BG synthesis, polymers/ surfactants are deployed as structure-directing agents, which self-assemble into micelles and create an ordered organic− inorganic mesophase. 30,35,73 Common MBG synthesis techniques utilize polymer templating (e.g., modified Stober, m i c r o e m u l s i o n o r e l e c t r o s p i n n i n g m e t h o d o l ogies).…”

“…30,35,73 Common MBG synthesis techniques utilize polymer templating (e.g., modified Stober, m i c r o e m u l s i o n o r e l e c t r o s p i n n i n g m e t h o d o l ogies). 1,35,42,44,45,47,49 Early sol−gel synthesis methods discovered that high-temperature treatment of sol−gel BGs resulted in decreased or lost porosity. 1 However, sol−gel BG calcination is necessary to incorporate metallic ions into the silica network, remove surfactants/polymers and to create wellordered, mesoporous morphology.…”