Strategy For Wound Healing Research Articles

Programmable Artificial Skins Accomplish Antiscar Healing with Multiple Appendage Regeneration.

Functional appendage regeneration is essential for skin rehabilitation, but it has always failed by current existing healing approaches, owing to their inefficacy in preventing disfiguring scars. In this study, a novel regeneration-directing artificial skin (RDAS) system is presented, which is based on the rational design of multi-layered hydrogels that closely mimic natural skin matrices. By leveraging the programmability and architectural rigidity of DNA components, without the need for exogenous cell transplantation, such RDAS effectively minimizes tissue fibrosis by accurately guiding the regenerative process in wound fibroblasts, enabling rapid scarless wound repair, restoration of dermal function, and successful in situ regeneration of multiple appendages, such as hair follicles (HFs), sebaceous glands (SGs), and sweat glands (SwGs). Therefore, the RDAS offers a cell-free antiscarring therapeutic strategy for regenerative wound healing, resulting in improved outcomes. This innovative approach holds great potential for future clinical applications and burn rehabilitation.

A triple-mode strategy combining low-temperature photothermal, photodynamic, and chemodynamic therapies for treating infectious skin wounds.

The skin is the first natural barrier of the human body. Bacterial infections severely hinder the healing process of skin wounds and pose a great threat to human health. Therefore, it is particularly urgent to develop new antimicrobial strategies for bacterial pathogen clearance and wound healing. In this study, a metal-organic framework (MOF), Fe-MIL88B-NH2, was incorporated with the photosensitizer indocyanine green (ICG) to construct composite nanoparticles (MOF@ICG NPs) with multiple antibacterial activities. Under mild near-infrared (NIR) irradiation, the photosensitizer ICG in the MOF@ICG NPs undergoes photothermal conversion (∼45 °C) and photodynamic reactions to generate heat and singlet oxygen (1O2). In addition, the Fenton reaction of the NPs with hydrogen peroxide (H2O2) in the bacterial infection microenvironment resulted in the generation of hydroxyl radicals (˙OH), thus achieving the three-mode combination of low-temperature photothermal therapy (PTT)/photodynamic therapy (PDT)/chemodynamic therapy (CDT). The in vitro experimental results showed that MOF@ICG MPs had excellent antibacterial properties and good cytocompatibility, with some ability to promote the migration of L-929 fibroblasts. Furthermore, under NIR irradiation, MOF@ICG NPs could significantly kill bacteria and promote skin wound healing according to the results of animal experiments. The wound healing rate reached 87.1% after 7 days of treatment. The research results break through the limitations of single-mode antibacterial technology and provide certain theoretical guidance and technical support for the research and development of new antibacterial materials.

Cold atmospheric plasma activation of human gingival fibroblasts for improved wound healing

Abstract Soft tissue regeneration plays a crucial role after oral surgery, as the successful healing of the soft tissue is a primary indicator of an efficacious intervention. Cold atmospheric plasma (CAP) has recently emerged as a promising therapeutic modality, exhibiting notable effects on cell migration and proliferation. Despite its potential, the dental application of CAP remains underexplored. This in vitro study aims to elucidate the impact of CAP activated medium on human gingival fibroblast responses, for future wound healing strategies. The study was divided into four parts: initial characterization of the plasma Jet, assessment of cell concentration, exploration of treatment distance effects, and treatment time dynamics. Human gingival fibroblasts were exposed to complete DMEM medium (without sodium pyruvate) activated with CAP at treatment distances of 2, 5, 7, and 9 mm, and treatment times of 15, 60, 120, 180, and 300 s for 1, 2 and 3 d of culture. The cell viability was evaluated using resazurin-based method, while wound healing dynamics was assessed via the scratch assay technique using phase-contrast microscopy. The cell morphology was characterised through fluorescence microscopy using propidium iodide and phalloidin staining, complemented by scanning electron microscopy. The results revealed that treatment distances and exposure times can influence the cell behaviour depending on the cell concentration. For the selected concentration of 1 × 104 cells ml−1, a treatment distance of 9 mm appeared to enhance human gingival fibroblast viability compared to a treatment distance of 2 mm and the control group. The images revealed adherent cells with a pattern typical of fibroblasts. However, no differences were observed for exposure times of 15 s and 180 s. The observed results further evidence that the exposure of the medium to the CAP device promoted an increase in cell viability, proliferation, and attachment in human gingival fibroblasts.

Strontium ranelate-loaded human hair keratin-hyaluronic acid hydrogel accelerates wound repair with anti-inflammatory and antioxidant properties

Inflammation and reactive oxygen species (ROS) production often accompany the repair of severe skin wounds, and the management of wounds has always been a clinical challenge, so the design of a hydrogel wound dressing with antioxidant and anti-inflammatory properties is of significant importance. This work incorporated strontium ranelate (SrR) into the keratin/hyaluronic acid (K/HA) hydrogel, which could scavenge ROS and reduce inflammation. The optimized hydrogel exhibits large pore size (217.2 μm), high porosity (57 %), high swelling rate (1759.52 %), and an elastic modulus (3.41 kPa). In the in vitro study, incorporating SrR into hydrogel effectively inhibited oxidative damage in mouse fibroblasts (L929) and improved anti-inflammatory effect in RAW264.7 cells stimulated by lipopolysaccharide. The in vivo study showed that, compared with the control group, the expression of ROS, IL-6 and TNF - α in the K/HA/0.5 mM SrR group were significantly reduced to 31.6 %, 39.7 % and 61.1 %, respectively. The in vivo evaluation in a full-thickness wound defect model demonstrated that K/HA/0.5 mM SrR hydrogel promotes wound healing by attenuating ROS levels, reducing inflammation, and promoting microangiogenesis. In summary, the excellent ROS scavenging and anti-inflammatory properties of SrR make the K/HA/SrR hydrogel a promising and effective strategy for wound healing.

Accelerating Oral Wound Healing Using Bilayer Biomaterial Delivery of FTY720 Immunotherapy.

Orofacial clefts are the most common congenital craniofacial anomaly. Adverse healing following cleft palate repair can lead to oronasal fistula (ONF), a persistent connection between the oral and nasal cavities. Although human allograft tissues are currently the gold standard for ONF repair, these methods carry risks of infection and rejection, often requiring surgical revision. Immunoregenerative therapies present a novel alternative approach to harness the body's immune response and enhance the wound healing environment. An FDA-approved immunomodulatory drug, FTY720, is repurposed to reduce lymphocyte egress and induce immune cell fate switching toward pro-regenerative phenotypes. In this study, a bilayer biomaterial system is engineered using Tegaderm to secure and control the delivery of FTY720-nanofiber scaffolds (FTY720-NF). The release kinetics of the bilayer FTY720-NF is optimized to maintain drug release for up to 7 days, ensuring safe transdermal absorption and tissue biodistribution. The comprehensive immunophenotyping results demonstrate a regenerative state transition in hybrid immune cells recruited to the wound site. Further, histological evaluations reveal a significant ONF closure in mice by day 7 following bilayer FTY720-NF implantation. These findings demonstrate the utility of immunomodulatory strategies for oral wound healing, better positing the field to develop more efficacious treatment options in pediatric patients.

NIR stimulated epigallocatechin gallate loaded polydopamine with enhanced antibacterial and ROS scavenging abilities for improved infectious wound healing

Infectious wound healing is complicated with and limited by infection and oxidative stress at the wound site. In recent years, various evidences suggest that nanozymes with multiple enzymatic activities have enabled the development of novel strategies for infectious wound healing. In this study, epigallocatechin gallate loaded polydopamine (P@E) was developed to act as a potent reactive oxygen species (ROS) scavenger for scavenging ROS, alleviating inflammatory responses, and promoting infectious wound healing. Combining with near infrared (NIR) irradiation, P@E presented excellent antibacterial ability of Escherichia coli (E. coli, 93.6%) and methicillin-resistant Staphylococcus aureus (MRSA, 87.6%). Specifically, P@E+NIR exhibited the most potent antioxidant, anti-inflammatory and cell proliferation behaviors through down-regulating intracellular ROS levels (81.9% and 94.3% for NIH3T3 and RAW264.7 respectively) and inducible nitric oxide synthase (iNOS) expression level (55.7%), and up-regulating the expression levels of arginase-1 (Arg-1, 71.4%), heat shock protein 70 (HSP70, 48.6%) and platelet endothelial cell adhesion molecule (CD31, 35.3%) compared to control group. Meanwhile, it also efficiently induced M2 directional polarization of lipopolysaccharide induced murine macrophages to achieve anti-inflammation, indicated by the down-regulation of CD86 (86.2%), and up-regulation of CD206 (85.6%). Significantly, it was also observed that P@E+NIR presented the excellent behaviors of inhibiting wound infection, alleviating wound inflammation, as well as promoting skin tissue repairing. Altogether, it has developed the strategy of using P@E combining with NIR irradiation for the synergistic enhanced healing of infectious skin wound, which can serve as a promising therapeutic strategy for its clinical treatment.

Engineering Injectable Coassembled Hydrogel by Photothermal Driven Chitosan-Stabilized MoS2 Nanosheets for Infected Wound Healing.

The application of enzyme-like molybdenum disulfide (MoS2) in tissue repair was confronted with stable dispersion, solubilization, and biotoxicity. Here, the injectable self-healing hydrogel was successfully designed using a step-by-step coassembly of chitosan and MoS2. Polyphenolic chitosan as a "structural stabilizer" of MoS2 nanosheets reconstructed well-dispersed MoS2@CSH nanosheets, which improved the biocompatibility of traditional MoS2, and strengthened its photothermal conversion and enzyme-like activities, guaranteeing highly efficient radical scavenging and antimicrobial properties. Furthermore, the polyphenol chitosan was employed again as a "molecular cross-linking agent" to form the injectable NIR-responsive MoS2@CSH hydrogel by accelerating hydrogen-bond interaction among chitosan and the multicross-linking reaction among polyphenols. The rapid self-healing ability was conducive to wound closure and dynamic adaptability. An experimental study on infected wound healing demonstrated that MoS2@CSH hydrogel could substantially eradicate bacteria and accelerate the angiogenesis of infected wounds. The photothermal-driven coassembly of MoS2 and polycation provided an alternative strategy for infected wound healing.

The Angiogenic Repertoire of Stem Cell Extracellular Vesicles: Demystifying the Molecular Underpinnings for Wound Healing Applications.

Stem cells-derived extracellular vesicles (SC-EVs) have emerged as promising therapeutic agents for wound repair, recapitulating the biological effects of parent cells while mitigating immunogenic and tumorigenic risks. These EVs orchestrate wound healing processes, notably through modulating angiogenesis-a critical event in tissue revascularization and regeneration. This study provides a comprehensive overview of the multifaceted mechanisms underpinning the pro-angiogenic capacity of EVs from various stem cell sources within the wound microenvironment. By elucidating the molecular intricacies governing their angiogenic prowess, we aim to unravel the mechanistic repertoire underlying their remarkable potential to accelerate wound healing. Additionally, methods to enhance the angiogenic effects of SC-EVs, current limitations, and future perspectives are highlighted, emphasizing the significant potential of this rapidly advancing field in revolutionizing wound healing strategies.

Amorphous zinc phosphate nanoclusters loaded polycarbonate thermosensitive hydrogel: An innovative strategy for promoting wound healing

Skin trauma is a matter of great concern for public health, emphasizing the importance of reconstructing the microenvironment at the trauma site to facilitate tissue regeneration. Therefore, the investigation of innovative wound dressings has significant research and clinical implications. In this study, we prepared a thermosensitive hydrogel based on a hydrophilic-hydrophobic-hydrophilic triblock polycarbonate polymer (PTP), and created a composite hydrogel, PTPH-AZP, by incorporating amorphous zinc phosphate (AZP) nanoclusters. We evaluated the effects of PTPH-AZP on human umbilical vein endothelial cells (HUVECs) and the ability to promote skin wound healing. According to the results, PTPH-AZP was found to promote the proliferation, migration, and tube formation of HUVECs through the sustained release of Zn2+ at appropriate concentrations. In vivo experiments demonstrated that in the early-mid stages of wound healing, PTPH-AZP promotes increases in Platelet Endothelial Cell Adhesion Molecule-1 (CD31) and α-Smooth Muscle Actin (α-SMA) content within the wound area, facilitating accelerated re-epithelialization and enhanced collagen deposition. In later healing stages, epidermal thickness in the PTPH-AZP treated group was significantly improved, aligning with surrounding intact skin with no instances of attenuated or hypertrophic scarring observed. The findings from the in vivo study suggested that PTPH-AZP may have a positive impact on vascularization and wound healing. In conclusion, this study presents a promising strategy for skin wound healing, highlighting the potential of PTPH-AZP as an effective therapeutic approach.

Investigating the Influence of Natural Compounds on the Healing Process of Wounds

Advancements in modern medicine have not fully resolved the complexities associated with wound healing, particularly for chronic wounds, such as diabetic ulcers and burn injuries. Effective wound management necessitates not only the regeneration of damaged tissue but also minimizing scar formation. In this context, natural compounds derived from plants have emerged as promising candidates for enhancing wound healing. Ethnobotanical research has demonstrated that various herbal extracts possess properties that could significantly improve wound healing outcomes. This review explores the potential of these natural compounds, focusing on their mechanisms of action, efficacy in clinical and preclinical studies, and the challenges that still need to be addressed. By synthesizing findings from traditional medicinal practices and contemporary scientific research, this review aims to provide a comprehensive understanding of how natural compounds can contribute to more effective wound healing strategies. In this review, widely used and studied plants are discussed, along with their ability to induce wound healing through all the phase and their mechanism of action.

Risk Factors for Postoperative Donor Site Complications in Radial Forearm Free Flaps.

Background and Objectives: The radial forearm free flap (RFFF) is the most commonly used flap for head and neck reconstruction. However, complications at the donor site are its major drawbacks. We aimed to identify the patient comorbidities and factors that predict donor site complications after RFFF. Materials and Methods: A retrospective chart review of consecutive patients who underwent RFFF reconstruction for head and neck cancer between 2015 and 2022 was performed. Demographic variables, clinical processes, and postoperative complications were assessed. All variables were analyzed using univariate and multivariate analyses. Results: Sixty-seven patients underwent RFFF reconstruction, and all received a split-thickness skin graft at the donor site. Twenty-five patients experienced delayed skin graft healing, whereas nine experienced sensory changes at the donor site. Hypertension and age had statistically significant negative effects on wound healing. The incidence of hand swelling was related to graft size, and the occurrence of paresthesia was significantly higher in diabetic patients and significantly lower in those with acellular dermal matrix (ADM). Conclusions: Patients with hypertension had a higher risk of prolonged wound healing after RFFF than their normotensive patients. Clinicians should pay particular attention to wound healing strategies in patients with hypertension. Additionally, better neuropathy care is recommended to achieve sensory recovery after RFFF in patients with diabetes. Using a skin graft with ADM could be a method to alleviate neurological symptoms.

Formulation of Dual-Functional Nonionic Cetomacrogol Creams Incorporated with Bacteriophage and Human Platelet Lysate for Effective Targeting of MDR P. aeruginosa and Enhanced Wound Healing.

Successful development of phage-based therapeutics and their utility predominantly depend on the mode and route of phage administration. Topical and site-directed phage application evokes minimal immune clearance and allows more phage-host adsorption, thereby ensuring higher phage efficacy. However, a notable drawback of conventional topical phage applications is the absence of sustained release. Occlusive emollients guarantee the controlled release of active pharmaceutical ingredients (APIs), thereby facilitating administration, preventing moisture loss, and acting as a skin barrier. In this study, we developed phage and human platelet lysate (h-PL) incorporated cetomacrogol-based creams for combined phage therapy and wound healing. The base material for phage immobilization was formulated by emulsifying paraffin and sterile water with cetomacrogol (emulsifying agent). Specifically, we incorporated a Pseudomonas aeruginosa-infecting lytic phage vB_PaeM_M12PA in the formulation and characterized its genome in this study. Cetomacrogol, a nonionic PEG (polyethylene glycol) based ether, rendered phage stability and allowed initial burst release followed by continuous controlled release of phages from the embedding matrix in the initial 6-8 h. Rheological studies showed that the material has elastic properties with storage moduli (G') values ranging from 109.51 ± 2.10 to 126.02 ± 3.13 kPa, indicating frequency-independent deformation. Platelet lysates in the cream acted as wound healing agents, and in vitro evaluation of cell migration and wound healing capacity of h-PL showed a significant enhancement by the sixth hour compared to untreated groups. The phage-incorporated cream showed sustained phage release in solid media and a significant reduction in bacterial growth in liquid cultures. In vivo wound healing studies in 6-week-old Wistar rats with full-thickness excision wounds and subsequent histopathological studies showed that the formulation enhanced wound healing and tissue restoration efficiency. In conclusion, the study unveils a promising approach for integrated phage therapy and wound healing strategies.

Bioinspired Collagen Scaffold Loaded with bFGF-Overexpressing Human Mesenchymal Stromal Cells Accelerating Diabetic Skin Wound Healing via HIF-1 Signal Pathway Regulated Neovascularization.

The healing of severe chronic skin wounds in chronic diabetic patients is still a huge clinical challenge due to complex regeneration processes and control signals. Therefore, a single approach is difficult in obtaining satisfactory therapeutic efficacy for severe diabetic skin wounds. In this study, we adopted a composite strategy for diabetic skin wound healing. First, we fabricated a collagen-based biomimetic skin scaffold. The human basic fibroblast growth factor (bFGF) gene was electrically transduced into human umbilical cord mesenchymal stromal cells (UC-MSCs), and the stable bFGF-overexpressing UC-MSCs (bFGF-MSCs) clones were screened out. Then, an inspired collagen scaffold loaded with bFGF-MSCs was applied to treat full-thickness skin incision wounds in a streptozotocin-induced diabetic rat model. The mechanism of skin damage repair in diabetes mellitus was investigated using RNA-Seq and Western blot assays. The bioinspired collagen scaffold demonstrated good biocompatibility for skin-regeneration-associated cells such as human fibroblast (HFs) and endothelial cells (ECs). The bioinspired collagen scaffold loaded with bFGF-MSCs accelerated the diabetic full-thickness incision wound healing including cell proliferation enhancement, collagen deposition, and re-epithelialization, compared with other treatments. We also showed that the inspired skin scaffold could enhance the in vitro tube formation of ECs and the early angiogenesis process of the wound tissue in vivo. Further findings revealed enhanced angiogenic potential in ECs stimulated by bFGF-MSCs, evidenced by increased AKT phosphorylation and elevated HIF-1α and HIF-1β levels, indicating the activation of HIF-1 pathways in diabetic wound healing. Based on the superior biocompatibility and bioactivity, the novel bioinspired skin healing materials composed of the collagen scaffold and bFGF-MSCs will be promising for healing diabetic skin wounds and even other refractory tissue regenerations. The bioinspired collagen scaffold loaded with bFGF-MSCs could accelerate diabetic wound healing via neovascularization by activating HIF-1 pathways.

Fusion protein of FGF21 and elastin-like peptide improves wound healing in diabetic mice via inflammation modulation, collagen synthesis, and vascular network formation

Chronic-healing skin wounds are a common complication in diabetic individuals. To alleviate patient suffering, there is a pressing demand for more effective strategies to expedite the repair of diabetic wounds. Fibroblast growth factor 21(FGF21) has been proven to accelerate wound healing, but its stability and ability to assist in the healing of diabetic ulcers have not met expectations. Therefore, we have fused FGF21 with an elastin-like peptide (ELP) to create a recombinant fusion protein (abbreviated as “ELF”) to increase the bioactivity and stability in vitro or in vivo. Our results demonstrated that ELF significantly improved the efficiency of FGF21 purification due to the inverse temperature responsive phase transition property of ELP. Meanwhile, the fusion strategy did not impair the structure of FGF21 or diminish its activity, as demonstrated by the highly similar secondary structure of ELF and FGF21, and their considerable inhibitory activity in the glucose consumption experiment of Huh-7 cells. An in vitro migration assay revealed that ELF promoted healing more effectively than either free FGF21 or ELP. Further in vivo study revealed the ability of ELF to improve skin wound healing quality, manifested by lower levels of inflammatory factors, more collagen formation and deposition, and the formation of robust vascular networks, though there was no significant difference in healing rate among the ELF, FGF21, and ELP groups. In conclusion, our study indicated that FGF21 and ELP fusion molecules could be developed as more efficient and cost-effective therapeutic strategies for diabetic wound healing.

Development and application of a mechanical arm-based in situ 3D bioprinting method for the repair of skin wounds

Current treatments for skin wounds typically involve multiple surgical procedures that require complex processes and expensive costs, making it difficult to achieve timely treatment in field environments. We developed an innovative in situ printing method, utilizing robotic arm control, to address the significant challenges of large-scale skin wound repair resulting from natural disasters such as earthquakes, fires, and explosions during relief efforts. Our portable 3D printing equipment, which integrates debridement, precise 3D scanning and modeling of wounds, and compatibility with cell-loaded bioink, facilitates rapid repair of large-area skin wounds in specialized field environments. Compared with traditional methods, this in situ printing method has significant advantages, including the ability to customize treatment according to the unique needs of the wound, achieve rapid healing, and the potential to reduce the total cost. We conducted experiments on rats with full-thickness dorsal skin defects and compared the performance of in situ bioprinting method with commercial skin defect repair dressings. Our results demonstrate that the in situ bioprinted skin achieved faster wound healing and more uniform re-epithelialization than the commercial dressing treatment. This study demonstrates the potential of in situ bioprinting method as a promising and effective strategy for rapid skin wound healing, especially for patients in remote environments where traditional wound treatment methods may not be readily available or practical.

Nanofibrous dressing with drug/electroactivity synergistic effect for wound healing

Although electrical stimulation (ES) and drugs are desirable for wound healing, dressings that combine ES and drugs are scarce. In this study, an electroactive drug-loaded nanofibrous dressing (PUE-Zn/AB@CA) was prepared by loading zinc/acetylene black nanoparticle particles (Zn/AB) in Puerarin/cellulose acetate (PUE/CA) nanofibres, respectively. Due to the different potentials, many galvanic couples can be formed between Zn and AB, generating electrical stimulation that promotes cell migration and proliferation. Benefiting from the synergistic effect of Zn/AB electrical stimulation and PUE, PUE-Zn/AB@CA exhibits excellent antioxidant, antibacterial, and anti-inflammatory properties. The whole-layer wound defect model experiment showed that PUE-Zn/AB@CA can significantly accelerate wound closure and promote granulation tissue formation, collagen deposition, and angiogenesis at the wound. Moreover, PUE-Zn/AB@CA could inhibit the inflammatory infiltration of M1-type macrophages in damaged wounds. In addition, flow cytometry and Western blot (WB) revealed that PUE-Zn/AB@CA could effectively down-regulate the lipopolysaccharide (LPS)-induced macrophage polarisation towards M1-type and reduce the protein level of pro-inflammatory cytokines (iNOS) in the cells. This work provided an effective wound healing strategy based on drug/electroactivity synergistic effects.

Promoting the healing of infected diabetic wound by nanozyme-containing hydrogel with anti-bacterial inflammation suppressing, ROS-scavenging and oxygen-generating properties.

Bacterial infections already pose a significant threat to skin wounds, especially in diabetic patients who have difficulty healing wounds. However, wound or bacterial infections are known to produce excess reactive oxygen species (ROS), and hypoxia may further hinder wound healing and the development of chronic wounds. In this study, a multifunctional hydrogel for ROS scavenging and bacterial inhibition was developed by cross-linking polyvinyl alcohol (PVA) and sodium alginate (SA) with graphene oxide (GO) loaded with silver-platinum hybrid nanoparticles (GO@Ag-Pt). The PVA/SA hydrogel loaded with GO@Ag-Pt exhibited the ability to scavenge different types of ROS, generate O2, and kill a broad spectrum of bacteria in vitro. The silver-platinum hybrid nanoparticles significantly increased the antibacterial ability against Escherichia coli and Staphylococcus aureus compared with silver nanoparticles (AgNps). GO@Ag-Pt loaded hydrogel was effective in treating infections caused by S.aureus, thereby significantly promoting wound healing during the inflammatory phase. Hydrogel therapy significantly reduced the level of ROS and alleviated inflammation levels. Notably, our ROS-scavenging, antibacterial hydrogels can be used to effectively treat various types of wounds, including difficult-to-heal diabetic wounds with bacterial infections. Thus, this study proposes an effective strategy for various chronic wound healing based on ROS clearance and bacteriostatic hydrogels.

Application of Mesenchymal Stem Cells and Exosome alone or Combination Therapy as a Treatment Strategy for Wound Healing.

The process of wound healing consists of multiple phases, and any disruptions in these phases can lead to the wound becoming chronic and impose heavy financial and psychological costs on the patient and a huge economic burden on the country's healthcare system. Various treatments such as drugs, matrix and scaffolds, blood products, cell therapy, and a combination of these treatments are used for wound healing. The use of mesenchymal stem cells (MSCs) is one of these methods that have produced appropriate responses in the healing of patients' wounds. MSCs by secreting growth factors, cytokines, chemokines, and RNAs elicit changes in cell proliferation, migration, growth, signaling, immunomodulation, and wound re-epithelialization process, and as a result, accelerate wound closure and wound healing. These cells can be isolated from different body sources with different cell characteristics and used directly on the wound site or by injection. In addition, MSCs-derived exosomes have attracted growing attention due to circumventing concerns relating to the direct use of MSCs. To increase the performance of MSCs, they can be used together with other compounds such as platelets, matrices, or scaffolds. This study examined the functions of MSCs in wound healing, as well as the vesicles they secrete, cellular and molecular mechanisms, and combined treatments with MSCs for wound healing.

Self-Assembled DNA Microflowers for Platelet-Derived Extracellular Vesicle Isolation and Infected Wound Healing.

Platelet-derived extracellular vesicles (PEVs) showing great potential in wound healing have attracted increasing attention recently. Nondestructive isolation and effective utilization strategies are highly conducive for PEVs developing into recognized therapeutic entities. Here, we present an efficient strategy for PEV isolation and bacterial infected wound healing based on self-assembled DNA microflowers. First, DNA microflowers are prepared using rolling circle amplification. Then, the hydrophobic interaction between cholesteryl modified on DNA microflowers and the phospholipid bilayer membrane of PEVs leads to the formation of a network structure with improved mechanical strength and the separation of PEVs from biological samples. Finally, controlled release of PEVs is achieved through bacterial-induced hydrogel degradation. In vitro experiments demonstrate the obtained DNA hydrogel with good cytocompatibility and therapeutic potential. Taken together, the DNA microflower-based hydrogels with bioadhesive, self-healing, tunable mechanical properties and bacteria-responsive behavior offer substantial potential for EV isolation and wound healing.

Hydrogel Loaded with Extracellular Vesicles: An Emerging Strategy for Wound Healing.

An increasing number of novel biomaterials have been applied in wound healing therapy. Creating beneficial environments and containing various bioactive molecules, hydrogel- and extracellular vesicle (EV)-based therapies have respectively emerged as effective approaches for wound healing. Moreover, the synergistic combination of these two components demonstrates more favorable outcomes in both chronic and acute wound healing. This review provides a comprehensive discussion and summary of the combined application of EVs and hydrogels to address the intricate scenario of wounds. The wound healing process and related biological mechanisms are outlined in the first section. Subsequently, the utilization of EV-loaded hydrogels during the wound healing process is evaluated and discussed. The moist environment created by hydrogels is conducive to wound tissue regeneration. Additionally, the continuous and controlled release of EVs from various origins could be achieved by hydrogel encapsulation. Finally, recent in vitro and in vivo studies reported on hydrogel dressings loaded with EVs are summarized and challenges and opportunities for the future clinical application of this therapeutic approach are outlined.