Multipronged Micelles–Hydrogel for Targeted and Prolonged Drug Delivery in Chronic Wound Infections

Abstract

Chronic diabetic wounds are a growing threat globally. Many aspects contribute to its deterioration, including bacterial infection, unbalanced microenvironment, dysfunction of cell repair, etc. In this work, we designed a multipronged micelles− hydrogel platform loaded with curcumin and rifampicin (CRMs− hydrogel) for bacteria-infected chronic wound treatment. The curcumin-and rifampicin-loaded micelles (CRMs) exhibited both MMP9-responsive and epidermal growth factor receptor (EGFR)targeting abilities. On the one hand, drugs could be released from micelles due to responsive disassembly by MMP9, a matrix metalloproteinase overexpressed in a chronic wound environment; on the other hand, CRMs showed specific targeting to EGFR on epithelial cells and fibroblasts and therefore increased intracellular drug delivery. The thermosensitive CRMs−hydrogel could form strong adhesion with the wound area and served as a suitable matrix for sustained release of CRMs directly at the wound bed, with excellent intracellular and extracellular bacterial elimination efficiency and wound healing promotion capability. We found that a single dose of CRMs−hydrogel achieved 99% antibacterial rate at the MRSA-infected diabetic wound, which effectively reduced inflammatory response and promoted the neovascularization and re-epithelialization process, with nearly half reduction of the skin barrier regeneration period. Collectively, our thermosensitive, MMP9-responsive, and targeted micelles−hydrogel nanoplatform is promising for chronic wound treatment.

Regenerated silk fibroin and alginate composite hydrogel dressings loaded with curcumin nanoparticles for bacterial-infected wound closure

“…Many factors, such as bacterial infection, microenvironment imbalance, and cellular repair dysfunction, can lead to wound deterioration and hinder the healing process [54] .…”

A Multifunctional, Tough, Stretchable, and Transparent Curcumin Hydrogel with Potent Antimicrobial, Antioxidative, Anti-inflammatory, and Angiogenesis Capabilities for Diabetic Wound Healing

“…26 Ma et al presented a Curand RIF-loaded micellar hydrogel with strong antibacterial ability, which shows a sterilization rate of 99% at the MRSAinfected diabetic wound, but there is a lack of exploration of the mechanical strength of these hydrogels. 19 These include bacterial infection, an unbalanced microenvironment, and dysfunction of cell repair. It is important to consider these factors simultaneously.…”

“…With a specific end goal to design and optimize novel efficient Cur-based wound-healing dressings, it is beneficial to incorporate other polymeric substances such as polyurethane, polysaccharides, − gelatin, poly­(vinyl alcohol), and pluronics into the structures of the Cur-based dressing, which will increase the contribution of Cur in wound healing: for example, mechanically tunable Cur-polyurethane, thiolated Cur-pluronic F127 micelles, Cur-coated magnetic nanoparticles hyaluronic acid, Cur-encapsulated fmoc-grafted chitosan and fmoc peptide hybrid hydrogel, organic–inorganic hybrids of CuS@C p–n junction, arginine-derived carbon quantum dots and polymeric Cur, water-soluble Cur, and esterification reactions . Various strategies have shown promising results in terms of antibacterial performance and enhanced angiogenesis by the sustained release of Cur.…”

Encapsulating Antibiotic and Protein-Stabilized Nanosilver into Sandwich-Structured Electrospun Nanofibrous Scaffolds for MRSA-Infected Wound Treatment

“…Since traditional dressings with strong adhesion are favorable for surrounding microorganisms colonization, leading to serious infection and inflammation, novel dressings including sponges, , hydrogels, , and films , have been developed to prevent microbial contamination. Among all of these formulations, electrospinning nanofiber membranes (ENMs) with nano/micro-scaled fibers resemble the steric structure of the extracellular matrix (ECM), which contributes to fitting onto the wound skin and is desirable for cell growth. , Besides, ENMs with high porosity promote the exchange of gas for tissue cells so as to maintain the moisture status around the wound. , As biomimetic carriers, ENMs may enable the efficient delivery of bioactive molecules to targeted wound tissues.…”

“…Since traditional dressings with strong adhesion are favorable for surrounding microorganisms colonization, leading to serious infection and inflammation, novel dressings including sponges, 3,28 hydrogels, 29,30 and films 31,32 have been developed to prevent microbial contamination. Among all of these formulations, electrospinning nanofiber membranes (ENMs) with nano/micro-scaled fibers resemble the steric structure of the extracellular matrix (ECM), which contributes to fitting onto the wound skin and is desirable for cell growth.…”