Unveiling the regenerative potency of human amniotic membrane-based bioactive matrices for wound healing application

Biocompatible nanomaterials have attracted enormous interest for biomedical applications. Carbonaceous materials, including carbon nanotubes (CNTs), have been widely explored in wound healing and other applications because of their superior physicochemical and potential biomedical properties to the nanoscale level. CNTs-based hydrogels are widely used for wound-healing and antibacterial applications. CNTs-based materials exhibited improved antimicrobial, antibacterial, adhesive, antioxidants, and mechanical properties, which are beneficial for the wound-healing process. This review concisely discussed the preparation of CNTs-based hydrogels and their antibacterial and wound-healing applications. The conductive potential of CNTs and their derivatives is discussed. It has been observed that the conductivity of CNTs is profoundly affected by their structure, temperature, and functionalization. CNTs properties can be easily modified by surface functionalization. CNTs-based composite hydrogels demonstrated superior antibacterial potential to corresponding pure polymer hydrogels. The accelerated wound healing was observed with CNTs-based hydrogels.

Bioactive functional scaffolds for stem cells delivery in wound healing and skin regeneration

Doxycycline (DOXY)-loaded hydroxyapatite (HAp) pectin hydrogel films were prepared for sustained drug release and wound healing application. A series of pectin-based, DOXY-loaded hydrogels were synthesized via a solution casting method. HAp at varying amounts was used as a filler to synthesize PEC/PVA/APTES/HAp (PPC-5, -10, -15, -20) hydrogels. SEM, FTIR, TGA, and XRD analyses verified the porous morphology, structural integrity, thermal stability and amorphous nature of the hydrogels, respectively. A biodegradation study of the hydrogel was conducted using phosphate buffer saline (PBS) and proteinase-K enzymatic solutions. Cell viability was evaluated using the MTT assay with HEK293 cells. Moreover, drug-loaded hydrogel dressings were developed and subjected to in vivo wound healing studies on albino mice. Excision wound infliction was created to produce a 5–6 mm wide and 2–3 mm deep cutaneous wound. Swelling of the hydrogel films was found to be inversely related to the concentrations of HAp. The hydrogels exhibited significant swelling profiles in distilled water with a maximum swelling of 2519% in 140 min, while the highest swelling was observed at pH 6 in both buffer and non-buffer solutions. Antibacterial studies indicated bactericidal activity of hydrogels against both Gram-positive (S. aureus) and Gram-negative (E. coli) bacteria. In vitro release of DOXY from the hydrogel matrix (PPC-10) revealed 88.57% drug release in PBS solution within 3.5 h. Wound healing studies exhibited exceptional healing tendency, with complete excision wound healing achieved in 8 days. In conclusion, the remarkable biocompatible, biodegradable and nontoxic pectin-based hydrogel systems are suitable for drug delivery, tissue engineering, wound healing, and other medico-biological applications.

640 Mussel-inspired Polydopamine-assisted Bromelain Immobilization onto Electrospun Fibrous Membrane for Potential Application as Wound Dressing

Natural polymers, or biopolymers, are widely utilized in regenerative medicine and tissue engineering. These polymers, derived from proteins, polysaccharides, and nucleic acids, serve as biomaterials for scaffolds, drug delivery systems, and bioactive materials that mimic the extracellular matrix. They offer advantages such as biocompatibility, biodegradability, versatility, and integration with gene therapy. Collagen, gelatin, chitosan, hyaluronic acid, fibrin, and alginate are commonly used natural polymers in regenerative medicine. They promote cell growth, tissue formation, wound healing, and tissue regeneration. Natural polymers also play a crucial role in controlled drug and gene delivery systems, providing safe and effective alternatives to synthetic polymers. Moreover, they contribute to developing bioactive and bio-functional materials, including hydrogels, which mimic natural biological processes and have applications in tissue engineering, drug delivery, and wound healing. Overall, natural polymers hold great promise for advancing regenerative medicine and tissue engineering. However, several challenges impede the widespread adoption and utilization of natural polymers in regenerative medicine. These challenges include variations in batch-to-batch composition, limited mechanical strength, rapid degradation rates, immunogenicity concerns, and difficulties achieving precise control over their properties. Overcoming these challenges necessitates a comprehensive understanding of the structure-function relationships of natural polymers and the development of innovative processing techniques to enhance their mechanical properties and stability. The future of natural polymers in regenerative medicine holds immense potential. Ongoing research efforts focus on refining their properties, tailoring their degradation rates, and integrating them with advanced technologies like 3D bioprinting and nanotechnology. By leveraging these advancements, natural polymers can be further optimized for specific tissue engineering applications, enabling the creation of patient-specific scaffolds, enhanced wound healing materials, and personalized drug delivery systems. Additionally, harnessing the innate bioactivity of natural polymers and their interactions with cells and tissues opens new avenues for the development of bioactive materials that promote tissue regeneration and healing.

Phosvitin-based hydrogels prepared in AmimCl under magnetic field treatment: Structural characteristics, biological functions, and application in skin wound healing

The main purpose of implementing biomaterials for regenerative medicine, e.g., in wound healing, is provision of topographical, biochemical, and biomechanical cues to regulate cell activities and to support cell attachment. In this regard, nature has already established a template, i.e., the extracellular matrix (ECM), which has been inspiring in the creation of different classes of biomaterials. Biomaterials that recapitulate the structure, composition, and dynamics of the ECM have been shown to be effective in tissue regeneration and wound healing applications. In particular, nanofiber materials that can simulate the ECM’s collagen nanofilamentous structure, in terms of topography and biochemistry, are highly attractive not only for regeneration of wounded tissue but also for modelling of human native skin to study disease, aging, and therapeutic conditions. Hybrid or composite nanofibers made of synthetic materials, natural materials or a blend of both can not only be employed as wound healing materials, but also as the basis of the epidermal and dermal layer in three-dimensional (3D) organotypic skin models, a new paradigm for modelling of human skin to identify the efficacy of therapeutics and wound healing processes. In this chapter, hybrid and composite nanofibrous materials are discussed from an ECM biomimicry standpoint (structural and biochemical biomimicry) that is crucial for their wound healing and skin modelling application. In collecting the presented information, we mainly considered the innovations carried out in the past five years to provide an updated overview on the ECM mimicking nanofibrous materials that have been applied as wound dressings, skin substitutes, and 3D skin models.

We disclose the use of hybrid materials featuring Au/Ag core/shell nanorods in porous chitosan/polyvinyl alcohol scaffolds for applications in tissue engineering and wound healing. The combination of Au and Ag in a single construct provides synergistic opportunities for optical activation of functions as near infrared laser tissue bonding, and remote interrogation to return parameters of prognostic relevance in wound healing monitoring. In particular, the bimetallic component ensures optical tunability, enhanced shelf life and photothermal stability, serves as a reservoir of germicidal silver cations, and changes in near-infrared and visible color according to the environmental level of oxidative stress. At the same time, the polymeric blend is ideal to bind connective tissue upon photothermal activation, and to support fabrication processes that provide high porosity, such as electrospinning, thus putting all the premises for cellular repopulation and antimicrobial protection.

Topical application of BRAF inhibitors has been shown to accelerate wound healing in murine models, which can be extrapolated into clinical applications. The aim of the study was to identify suitable pharmacological targets of BRAF inhibitors and elucidate their mechanisms of action for therapeutic applicability in wound healing, by employing bioinformatics tools including network pharmacology and molecular docking. The potential targets for BRAF inhibitors were obtained from SwissTargetPrediction, DrugBank, CTD, Therapeutic Target Database, and Binding Database. Targets of wound healing were obtained using online databases DisGeNET and OMIM (Online Mendelian Inheritance in Man). Common targets were found by using the online GeneVenn tool. Common targets were then imported to STRING to construct interaction networks. Topological parameters were assessed using Cytoscape and core targets were identified. FunRich was employed to uncover the signaling pathways, cellular components, molecular functions, and biological processes in which the core targets participate. Finally, molecular docking was performed using MOE software. Key targets for the therapeutic application of BRAF inhibitors for wound healing are peroxisome proliferator-activated receptor γ, matrix metalloproteinase 9, AKT serine/threonine kinase 1, mammalian target of rapamycin, and Ki-ras2 Kirsten rat sarcoma viral oncogene homolog. The most potent BRAF inhibitors that can be exploited for their paradoxical activity for wound healing applications are Encorafenib and Dabrafenib. By using network pharmacology and molecular docking, it can be predicted that the paradoxical activity of BRAF inhibitors can be used for their potential application in wound healing.

Biological scaffolds have been widely employed in wound healing applications, while their practical efficiency is compromised by insufficient oxygen delivery to the 3-dimensional constructs and inadequate nutrient supply for the long-term healing process. Here, we present an innovative living Chinese herbal scaffold to provide a sustainable oxygen and nutrient supply for promoting wound healing. Through a facile microfluidic bioprinting strategy, a traditional Chinese herbal medicine (Panax notoginseng saponins [PNS]) and a living autotrophic microorganism (microalgae Chlorella pyrenoidosa [MA]) were successfully encapsulated into the scaffolds. The encapsulated PNS could be gradually released from the scaffolds, which promoted cell adhesion, proliferation, migration, and tube formation invitro. In addition, benefiting from the photosynthetic oxygenation of the alive MA, the obtained scaffolds would produce sustainable oxygen under light illumination, exerting a protective effect against hypoxia-induced cell death. Based on these features, we have demonstrated through invivo experiments that these living Chinese herbal scaffolds could efficiently alleviate local hypoxia, enhance angiogenesis, and thereby accelerate wound closure in diabetic mice, indicating their great potential in wound healing and other tissue repair applications.

Objective: This study aims to develop and characterize electroactive hydrogels based on reduced bacterial cellulose (BC) and Ti3C2T x -MXene for their potential application in wound healing and real-time monitoring. Impact Statement: The integration of Ti3C2T x -MXene into BC matrices represents a novel approach to creating multifunctional hydrogels that combine biocompatibility, electrical conductivity, and mechanical durability. These properties make the hydrogels promising candidates for advanced wound care and real-time monitoring applications. Introduction: Wound healing requires materials that support cell growth, promote tissue regeneration, and enable real-time monitoring. MXenes, a class of 2-dimensional materials, offer unique electrical and mechanical properties, making them suitable for biomedical applications. This study explores the integration of Ti3C2T x -MXene with BC, a biopolymer known for its excellent biocompatibility and mechanical strength, to create electroactive composite hydrogel films for advanced wound care. Methods: Ti3C2T x -MXene was synthesized by etching Ti3AlC2 with hydrofluoric acid and integrated into BC pellicles produced by Gluconacetobacter xylinum. The composite hydrogel films underwent characterization through x-ray diffraction (XRD), x-ray photoelectron spectroscopy (XPS), Fourier transform infrared spectroscopy (FTIR), and thermogravimetric analysis (TGA) to determine structural, chemical, and thermal properties. Mechanical testing assessed tensile and compressive strengths. Biological assessments, including cell viability, hemolysis rate, and protein expression, evaluated biocompatibility and regenerative potential. Results: XRD confirmed the crystallographic structure of MXene and BC composite film. XPS and FTIR validated the successful incorporation of MXene into the film matrix. Composite hydrogel films demonstrated a tensile strength of 3.5 MPa and a compressive strength of 4.2 MPa. TGA showed stability up to 350 °C, and the electrical conductivity reached 9.14 × 10-4 S/m, enabling real-time monitoring capabilities. Cell viability exceeded 95%, with a hemolysis rate below 2%. Protein expression studies revealed the ability to promote skin regeneration through collagen I, K10, K5, and filaggrin expression. Conclusion: The BC/MXene composite hydrogel films exhibit important potential as electronic-skin patches for accelerating wound healing and enabling real-time monitoring. Their unique combination of mechanical durability, electrical conductivity, and biocompatibility highlights their promise for advanced wound care applications.

Plant-derived medicinal materials have significant potential and promising applications in wound healing and skin regeneration. This study aims to develop a plant-based extract hydrogel from Bletilla striata (Thunb.Reichb.f.), specifically a glucosyloxybenzyl 2-isobutylmalates extract (B), and characterize its potential effects on wound healing. We synthesized the hydrogel using carbomer (C), glycerol (G), and triethanolamine (T) as the matrix, incorporating B into the hydrogel base, and evaluated its physical and chemical properties. In vitro tests assessed the biocompatibility of the glucosyloxybenzyl 2-isobutylmalates-carbomer-glycerol-triethanolamine (B-CGT) hydrogel and its effects on cell proliferation, migration, and adhesion. Animal model experiments evaluated its potential to promote wound healing. The results showed that the prepared B-CGT hydrogel possessed a good three-dimensional network structure and stability, demonstrating significant free radical scavenging capacity in antioxidant tests. In cell experiments, the B-CGT hydrogel exhibited no potential cytotoxicity and showed good hemocompatibility and promotion of cell proliferation. Animal experiments indicated that wounds treated with the B-CGT hydrogel healed significantly faster, with improved formation of new epithelial tissue and collagen. This study suggests that the developed B-CGT hydrogel is a promising candidate for wound dressings, with excellent physicochemical properties and controlled drug release capabilities, effectively promoting the wound healing process.

The design of biopolymers matrices for incorporating bioactive compounds represents a valuable technique for various biomedical and packaging applications. Propolis has developed as a natural byproduct from beekeeping for wound healing, food packaging, and food production applications. The current review focuses on the various composites prepared from propolis with polysaccharides like cellulose, chitosan, starch, and alginate, where the chemistry, synthesis, and application are seriously discussed. This study found that polysaccharide composite matrix with propolis may provide an appropriate platform for different applications such as wound healing and adequate biodegradable packaging. Using polysaccharide composite matrix with propolis is a promise policy for biodegradable active packaging upgrading and wound healing applications.

This systematic review aims to examine the existing literature on the therapeutic potential of medicinal plants to improve caudal fin regeneration and wound healing in zebrafish (Danio rerio), focusing on uncovering their pharmacological properties and potential use in enhancing tissue repair and regeneration. A thorough review of suitable and eligible full-text articles was performed on PubMed, Scopus, Web of Science, and Google Scholar from 1 st January 2014 to 31 st December 2024. These articles were searched using the Medical Subject Headings terms "zebrafish," "zebrafish larvae," "zebrafish embryo," "angiogenesis," "Medicinal plants," "Natural products," "Fin regeneration," "wound healing," and "inflammation." Here, 520 articles on medicinal plants and their potential in caudal fin regeneration and wound healing in zebrafish were identified across the databases searched, of which 26 were included in this study following screening. After thoroughly reviewing the articles, some were found to have used multiple medicinal plants. Thus, 38 medicinal plants were found to have promoted effects on zebrafish caudal fin regeneration and wound healing, and 21 revealed no effects on either caudal fin regeneration and wound healing. This systematic review explores the therapeutic potential of medicinal plants in caudal fin regeneration and wound healing in a zebrafish model. The results show a promising effect of various plant species in enhancing fin regeneration and wound healing. Further research is needed to understand the molecular mechanisms and to translate these findings into clinical applications for human wound healing and regenerative medicine.

Healing is a specific biological process related to the general phenomenon of growth and tissue regeneration and is a process generally affected by several systemic conditions or as detrimental side-effects of chemotherapy- and radiotherapy-induced inflammation of the oral mucosa. The objectives of this study is to evaluate the novel chitosan based functional drug delivery systems, which can be successfully incorporated into “dual action bioactive restorative materials”, capable of inducing in vitro improved wound healing prototype and containing an antibiotic, such as nystatin, krill oil as an antioxidant and hydroxyapatite as a molecular bone scaffold, which is naturally present in bone and is reported to be successfully used in promoting bone integration when implanted as well as promoting healing. The hydrogels were prepared using a protocol as previously reported by us. The physico-chemical features, including surface morphology (SEM), release behaviors, stability of the therapeutic agent-antioxidant-chitosan, were measured and compared to the earlier reported chitosan-antioxidant containing hydrogels. Structural investigations of the reactive surface of the hydrogel are reported. Release of nystatin was investigated for all newly prepared hydrogels. Bio-adhesive studies were performed in order to assess the suitability of these designer materials. Free radical defense capacity of the biomaterials was evaluated using established in vitro model. The bio-adhesive capacity of the materials in the in vitro system was tested and quantified. It was found that the favorable synergistic effect of free radical built-in defense mechanism of the new functional materials increased sustainable bio-adhesion and therefore acted as a functional multi-dimensional restorative material with potential application in wound healing in vitro.