Disclosure of a Promising Lead to Tackle Complicated Skin and Skin Structure Infections: Antimicrobial and Antibiofilm Actions of Peptide PP4-3.1

Efficient antibiotics are being exhausted, which compromises the treatment of infections, including complicated skin and skin structure infections (cSSTI) often associated with multidrug resistant (MDR) bacteria, methicillin-resistant S. aureus (MRSA) being the most prevalent. Antimicrobial peptides (AMP) are being increasingly regarded as the new hope for the post-antibiotic era. Thus, future management of cSSTI may include use of peptides that, on the one hand, behave as AMP and, on the other, are able to promote fast and correct skin rebuilding. As such, we combined the well-known cosmeceutical pentapeptide-4 (PP4), devoid of antimicrobial action but possessing collagenesis-boosting properties, with the AMP 3.1, to afford the chimeric peptide PP4-3.1. We further produced its N-methyl imidazole derivative, MeIm-PP4-3.1. Both peptide-based constructs were evaluated in vitro against Gram-negative bacteria, Gram-positive bacteria, and Candida spp. fungi. Additionally, the antibiofilm activity, the toxicity to human keratinocytes, and the activity against S. aureus in simulated wound fluid (SWF) were assessed. The chimeric peptide PP4-3.1 stood out for its potent activity against Gram-positive and Gram-negative bacteria, including against MDR clinical isolates (0.8 ≤ MIC ≤ 5.7 µM), both in planktonic form and in biofilm matrix. The peptide was also active against three clinically relevant species of Candida fungi, with an overall performance superior to that of fluconazole. Altogether, data reveal that PP4-3.1 is as a promising lead for the future development of new topical treatments for severe skin infections.

Recent Progress in Intelligent Wearable Sensors for Health Monitoring and Wound Healing Based on Biofluids

The intelligent wearable sensors promote the transformation of the health care from a traditional hospital-centered model to a personal portable device-centered model. There is an urgent need of real-time, multi-functional, and personalized monitoring of various biochemical target substances and signals based on the intelligent wearable sensors for health monitoring, especially wound healing. Under this background, this review article first reviews the outstanding progress in the development of intelligent, wearable sensors designed for continuous, real-time analysis, and monitoring of sweat, blood, interstitial fluid, tears, wound fluid, etc. Second, this paper reports the advanced status of intelligent wound monitoring sensors designed for wound diagnosis and treatment. The paper highlights some smart sensors to monitor target analytes in various wounds. Finally, this paper makes conservative recommendations regarding future development of intelligent wearable sensors.

Protease-Triggered Release of Stabilized CXCL12 from Coated Scaffolds in an Ex Vivo Wound Model

Biomaterials are designed to improve impaired healing of injured tissue. To accomplish better cell integration, we suggest to coat biomaterial surfaces with bio-functional proteins. Here, a mussel-derived surface-binding peptide is used and coupled to CXCL12 (stromal cell-derived factor 1α), a chemokine that activates CXCR4 and consequently recruits tissue-specific stem and progenitor cells. CXCL12 variants with either non-releasable or protease-mediated-release properties were designed and compared. Whereas CXCL12 was stabilized at the N-terminus for protease resistance, a C-terminal linker was designed that allowed for specific cleavage-mediated release by matrix metalloproteinase 9 and 2, since both enzymes are frequently found in wound fluid. These surface adhesive CXCL12 derivatives were produced by expressed protein ligation. Functionality of the modified chemokines was assessed by inositol phosphate accumulation and cell migration assays. Increased migration of keratinocytes and primary mesenchymal stem cells was demonstrated. Immobilization and release were studied for bioresorbable PCL-co-LC scaffolds, and accelerated wound closure was demonstrated in an ex vivo wound healing assay on porcine skin grafts. After 24 h, a significantly improved CXCL12-specific growth stimulation of the epithelial tips was already observed. The presented data display a successful application of protein-coated biomaterials for skin regeneration.

This Review Recent Advances in Chitosan and Alginate‐Based Hydrogels for Wound Healing Application

Wound healing is a complicated yet necessary event that takes place in both animals and human beings for the body to repair itself due to injury. Wound healing involves various stages that ensure the restoration of the injured tissue at the end of the process. Wound dressing material acts as a protective extracellular barrier against potential damage to the injury and microbial invasion. Naturally, polysaccharides (chitosan and alginate) have inherent properties that have made them attractive for their usage in wound healing therapy. Alginate and chitosan have been used to develop novel wound healing and smart biomaterials due to various functionalities such as reducing swelling, non-toxic nature, biocompatibility, antimicrobial potential, and maintenance moist environment, ability to absorb wound fluid, and skin regeneration promotion. Functionalization of polysaccharides is one of the many approaches that have been used to modify and enhance the wound healing properties of these biomaterials. Many studies have been done to modify the polysaccharide hydrogels. Some of these are highlighted in this paper. The designing and development of smart hydrogels that react to their environment have recently sparked a significant scientific and pharmaceutical interest. Smart hydrogel development has been the primary focal area for developing highly advanced and sophisticated wound healing therapeutic technologies. This paper seeks to comprehensively shed light on the advancements of functionalized chitosan and alginate-based hydrogels and their applicability in wound healing therapeutics. In addition to this, thus identifying critical drawbacks faced in existing hydrogel systems and how prospective technologies enable digitally controlled bio-platforms coupled with biomaterials to improve wound care. This review hopes to stimulate and encourage researchers to identify future avenues worth investigation.

Curdlan-Based Hydrogels for Potential Application as Dressings for Promotion of Skin Wound Healing—Preliminary In Vitro Studies

The aim of this work was to establish whether novel curdlan-based hydrogels enriched with Ca2+ ions may be considered as potential candidates for dressings, for the acceleration of skin wound healing. Firstly, biomaterials were allocated for evaluation of structural and mechanical properties. Subsequently, the ability of hydrogels to absorb simulated wound fluid and water vapor permeability, as well their capacity to release calcium ions, was evaluated. The biocompatibility of biomaterials was assessed using normal human skin fibroblasts. Importantly, the main features of the obtained curdlan-based hydrogels were compared with those of KALTOSTAT® (a commercial calcium sodium alginate wound dressing). The obtained results showed that curdlan-based biomaterials possessed a mesoporous structure (pore diameter ranged from 14–48 nm) and exhibited a good ability to absorb simulated wound fluid (swelling ratio close to 974–1229%). Moreover, in a wet state, they enabled proper water vapor transmission rate (>2000 g/m2/day), thanks to their hydrogel structure. Finally, it was found that biomaterial composed of 11 wt.% of curdlan (Cur_11%) possessed the most desirable biological properties in vitro. It released a beneficial amount of calcium ions to the aqueous environment (approximately 6.12 mM), which significantly enhanced fibroblast viability and proliferation. Taking into account the beneficial properties of Cur_11% biomaterial, it seems justified to subject it to more advanced cell culture experiments in vitro and to in vivo studies in order to determine its precise influence on skin wound healing.