Full-thickness Wounds Research Articles

Development of mADM-collagen wound dressings for mimicking native skin architecture to enhance skin wound healing

Acellular dermal matrix (ADM) is one of the most promising scaffold materials due to its ability to retain natural extracellular matrix structure. Micronized acellular dermal matrix (mADM) was prepared with no intact cell nuclei and preserved growth factors by High Hydrostatic Pressure (HHP) approach. And mADM-collagen wound dressings were developed with different proportion of type I collagen and recombinant humanized type III collagen. The porous structure of the mADM-collagen wound dressings made them a good candidate for preventing excessive fluid accumulation, while the collagens with gel-like texture combined with mADM powder to form pasty texture wound dressing, which preserving the moisture at the wound site. Moreover, the paste texture of the mADM-collagen wound dressing was easy to reshape to conform any wound shapes and body contours. Furthermore, the resulted mADM-collagen wound dressings showed good biocompatibility by supporting fibroblasts adhesion and proliferation in vitro. Subsequently, a murine model of full-thickness skin wounds was employed to assess its effects on wound healing. Notably, mADM-75% Col-I exhibited superior effects throughout the wound healing process, specifically it promoted neovascularization, skin appendage growth and new skin regeneration. This formulation closely mimicked the collagen ratio found in healthy skin, facilitating the favorable wound repair. These results indicated the superior performance of this mADM-collagen wound dressing providing an optimal environment for wound healing.Graphical

Developing multifunctional pectin-based hydrogel for wound dressing: In silico, in vitro and in vivo evaluation

Multifunctional hydrogel wound dressing with high hemostatic, antioxidant, and self-healing activity is desirable in clinical applications. In this contribution, we developed two distinct hydrogel formulations, namely PZ and PTBA, by employing low methoxyl pectin (P), zeolite, or 2-thiobarbituric acid (TBA) for sustained release of procaine (PC) in a controlled manner up to 40 h. These hydrogel systems (PZ and PTBA) utilize dynamic reversible hydrogen bonds between the components and a metal coordination bond between carboxyl acid groups of pectin chains and Ca2+ to confer self-healing properties, as demonstrated by molecular dynamics (MD) and rheological analyses. Moreover, PZ and PTBA hydrogels possess superior antioxidant, hemostasis, biocompatibility, and antibacterial activities. The data from the mouse skin incision model and infected full-thickness skin wound model demonstrated the highest wound closure rate (wound closure area per day) was achieved by the PZ (4.72) and PTBA (4.62) groups on day 21, which was better than the control (4.2) and Kaltostat groups (4.05) (p < 0.05). PZ and PTBA’s effectiveness in wound closure and acceleration of the wound healing process, highlighting its significant potential in wound management.

Streamlining Skin Regeneration: A Ready-To-Use Silk Bilayer Wound Dressing.

Silk proteins have been highlighted in the past decade for tissue engineering (TE) and skin regeneration due to their biocompatibility, biodegradability, and exceptional mechanical properties. While silk fibroin (SF) has high structural and mechanical stability with high potential as an external protective layer, traditionally discarded sericin (SS) has shown great potential as a natural-based hydrogel, promoting cell-cell interactions, making it an ideal material for direct wound contact. In this context, the present study proposes a new wound dressing approach by developing an SS/SF bilayer construct for full-thickness exudative wounds. The processing methodology implemented included an innovation element and the cryopreservation of the SS intrinsic secondary structure, followed by rehydration to produce a hydrogel layer, which was integrated with a salt-leached SF scaffold to produce a bilayer structure. In addition, a sterilization protocol was developed using supercritical technology (sCO2) to allow an industrial scale-up. The resulting bilayer material presented high porosity (>85%) and interconnectivity while promoting cell adhesion, proliferation, and infiltration of human dermal fibroblasts (HDFs). SS and SF exhibit distinct secondary structures, pore sizes, and swelling properties, opening new possibilities for dual-phased systems that accommodate the different needs of a wound during the healing process. The innovative SS hydrogel layer highlights the transformative potential of the proposed bilayer system for biomedical therapeutics and TE, offering insights into novel wound dressing fabrication.

Cutaneous Wound Healing and the Effects of Cannabidiol.

Cutaneous wounds, both acute and chronic, begin with loss of the integrity, and thus barrier function, of the skin. Surgery and trauma produce acute wounds. There are 22 million surgical procedures per year in the United States alone, based on data from the American College of Surgeons, resulting in a prevalence of 6.67%. Acute traumatic wounds requiring repair total 8 million per year, 2.42% or 24.2 per 1000. The cost of wound care is increasing; it approached USD 100 billion for just Medicare in 2018. This burden for wound care will continue to rise with population aging, the increase in metabolic syndrome, and more elective surgeries. To heal a wound, an orchestrated, evolutionarily conserved, and complex series of events involving cellular and molecular agents at the local and systemic levels are necessary. The principal factors of this important function include elements from the neurological, cardiovascular, immune, nutritional, and endocrine systems. The objectives of this review are to provide clinicians engaged in wound care and basic science researchers interested in wound healing with an updated synopsis from recent publications. We also present data from our primary investigations, testing the hypothesis that cannabidiol can alter cutaneous wound healing and documenting their effects in wild type (C57/BL6) and db/db mice (Type 2 Diabetes Mellitus, T2DM). The focus is on the potential roles of the endocannabinoid system, cannabidiol, and the important immune-regulatory wound cytokine IL-33, a member of the IL-1 family, and connective tissue growth factor, CTGF, due to their roles in both normal and abnormal wound healing. We found an initial delay in the rate of wound closure in B6 mice with CBD, but this difference disappeared with time. CBD decreased IL-33 + cells in B6 by 70% while nearly increasing CTGF + cells in db/db mice by two folds from 18.6% to 38.8% (p < 0.05) using a dorsal wound model. We review the current literature on normal and abnormal wound healing, and document effects of CBD in B6 and db/db dorsal cutaneous wounds. CBD may have some beneficial effects in diabetic wounds. We applied 6-mm circular punch to create standard size full-thickness dorsal wounds in B6 and db/db mice. The experimental group received CBD while the control group got only vehicle. The outcome measures were rate of wound closure, wound cells expressing IL-33 and CTGF, and ILC profiles. In B6, the initial rate of wound closure was slower but there was no delay in the time to final closure, and cells expressing IL-33 was significantly reduced. CTGF + cells were higher in db/bd wounds treated with CBD. These data support the potential use of CBD to improve diabetic cutaneous wound healing.

An Injectable Hydrogel with Ultrahigh Burst Pressure and Innate Antibacterial Activity for Emergency Hemostasis and Wound Repair.

Uncontrolled bleeding and wound infections following severe trauma pose significant challenges for existing tissue adhesives, primarily due to their weak wet adhesion, slow adhesion formation, cytotoxicity concerns, and lack of antibacterial properties. Herein, an injectable hydrogel (denoted as ES gel) with rapid, robust adhesive sealing and inherent antibacterial activity based on ε-polylysine and a poly(ethylene glycol) derivative is developed. The engineered hydrogel exhibits rapid gelation behavior, high mechanical strength, strong adhesion to various tissues, and can sustain an ultrahigh burst pressure of 450mmHg. It also presents excellent biocompatibility, biodegradability, antibacterial properties, and on-demand removability. Significantly improved hemostatic efficacy of ES gel compared to fibrin glue is demonstrated using various injury models in rats and rabbits. Remarkably, the adhesive hydrogel can effectively halt lethal non-compressible hemorrhages in visceral organs (liver, spleen, and heart) and femoral artery injury models in fully anticoagulated pigs. Furthermore, the hydrogel outperforms commercial products in sutureless wound closure and repair in the rat liver defect, skin incision, and infected full-thickness skin wound models. Overall, this study highlights the promising clinical applications of ES gel for managing uncontrolled hemorrhage, sutureless wound closure, and infected wound repair.

Tranexamic acid-loaded catechol-modified hyaluronic acid/carboxymethyl chitosan double cross-linked porous gel micropowders for rapid hemostasis and wound healing

Acquiring rapid and effective hemostasis remains a critical clinical challenge. Current researches focus on concentrating blood components to speed up the hemostatic while ignore the effect of anti-fibrinolysis in promoting blood coagulation. Herein, we designed a novel tranexamic acid (TA)-loaded physicochemical double cross-linked multifunctional catechol-modified hyaluronic acid-dopamine/carboxymethyl chitosan porous gel micropowders (TA&Fe3+@HA-DA/CMCS PGMs) for rapid hemostasis and wound healing. TA&Fe3+@HA-DA/CMCS PGMs exhibited high water absorption rate (505.9 ± 62.1 %) and rapid hemostasis (79 ± 4 s) in vivo. Catechol groups, Fe3+ and the protonated amino groups of CMCS induced bacterial death. Moreover, TA&Fe3+@HA-DA/CMCS PGMs displayed sufficient adhesion to a variety of wet rat tissues. TA&Fe3+@HA-DA/CMCS PGMs on various bleeding wounds, including rat liver injury and tail severed models showed excellent hemostasis performance. The TA&Fe3+@HA-DA/CMCS PGMs could promote the healing of full-thickness skin wounds on the backs of rats. The advantages of TA&Fe3+@HA-DA/CMCS PGMs including rapid hemostasis, effective wound healing, good tissue adhesion, antibacterial properties and ease of use make it potentially valuable in clinical application.

Modification of mesenchymal stromal cells with silibinin-loaded PLGA nanoparticles improves their therapeutic efficacy for cutaneous wound repair

The use of mesenchymal stromal cells (MSCs) for treating chronic inflammatory disorders, wounds, and ischemia-reperfusion injuries has shown improved healing efficacy. However, the poor survival rate of transplanted cells due to oxidative stress in injured or inflamed tissue remains a significant concern for MSC-based therapies. In this study, we developed a new approach to protect MSCs from oxidative stress, thereby improving their survival in a wound microenvironment and enhancing their therapeutic effect. We produced PLGA nanoparticles loaded with the cytoprotective phytochemical silibinin (SBN), and used them to modify MSCs. Upon internalization, these nanoformulations released SBN, activating the Nrf2/ARE signaling pathway, resulting in threefold reduction in intracellular ROS content and improved cell survival under oxidative stress conditions. Modification of MSCs with SBN-loaded PLGA nanoparticles increased their survival upon transplantation to full-thickness cutaneous wounds and improved wound healing. This study suggests that MSC modification with cytoprotective nanoparticles could be a promising approach for improving wound healing.

Pluronic F127 composite hydrogel for the repair of contraction suppressed full-thickness skin wounds in a rabbit model

Hydrogels are commonly used as carriers for cell delivery due to their similarities to the extracellular matrix. A contraction-suppressed full-thickness wound model was used to evaluate the therapeutic potential of Pluronic F127 (PF127) hydrogel loaded with adipose-derived stromal vascular fraction (AdSVF), mesenchymal stem cells (AdMSC), and conditioned media (AdMSC-CM) for the repair of wounds in a rabbit model. The experimental study was conducted on forty-eight healthy adult New Zealand white rabbits randomly divided into eight groups with six animals each and treated with AdSVF, AdMSC, and AdMSC-CM as an injectable or topical preparation. The healing potential of different adipose-derived cell-based and cell-free therapeutics was evaluated based on percentage wound healing, period of epithelialization, epidermal thickness, scar evaluation, histopathology analysis, histochemical evaluation, immunohistochemistry (collagen type I), and hydroxyproline assay by comparing with the positive and negative control. Collagen density analysis using different staining methods, immunohistochemistry, and hydroxyproline assay consistently showed that delivering AdMSC and AdMSC-CM in PF127 hydrogel enhanced epithelialization, collagen production, and organization, contributing to improved tissue strength and quality. Even though allogeneic AdSVF was found to promote wound healing in rabbits, it has a lower potential than AdMSC and AdMSC-CM. The wound healing potential of AdMSC and AdMSC-CM was enhanced when loaded in PF127 hydrogel and applied topically. Even though wounds treated with AdMSC outperformed AdMSC-CM, a significant difference in the healing quality was not observed in most instances, indicating almost similar therapeutic potential. The findings indicate that the wound healing potential of AdMSC and AdMSC-CM was enhanced when loaded in PF127 hydrogel and applied topically. These treatments promoted collagen production, tissue organization, and epidermal regeneration, ultimately improving overall healing outcomes.

Macrochannel-aligned cryogels with oxygen release and antibacterial properties for MRSA-infected diabetic wound healing

Wounds in diabetic patients suffer from bacterial infection, reduced angiogenesis, and inadequate oxygen supply, which prolong healing time and form chronic wounds. Long-term hypoxia is one of the main causes of delayed wound healing. Therefore, it is particularly urgent to develop new dressings with oxygen release and antibacterial properties for the infected diabetic wound. In this paper, we developed oxygen-releasing and macrochannel-aligned cryogels based on acylhydrazone bond cross-linking between the adipic dihydrazide grafted hyaluronic acid (AHA) and oxidized dextran (OD). The aligned macroporous structure of cryogels formed by the unidirectional freezing technique is favorable for the release of oxygen. The incorporated calcium peroxide (CPO) can react with water to produce oxygen and hydrogen peroxide (H2O2), which can provide good antibacterial properties, while excess H2O2 can be decomposed into oxygen by catalase (CAT), achieving oxygen release for up to 10 days. The macrochannel-aligned cryogels have suitable mechanical properties, oxygen release property, good biological property, and antibacterial property resulting from H2O2 release. In the MRSA-infected diabetic full-thickness defect wound model, compared to the commercial dressing, the cryogel showed excellent bactericidal property and better wound healing by providing oxygen, regulating inflammation, accelerating collagen deposition, and promoting granulation tissue formation and vascularization. In brief, this study developed an efficient oxygen-releasing and antibacterial cryogel with an aligned macroporous structure, which may provide a new strategy for the management of chronic hypoxic infected diabetic wounds.

Multi-dynamic-bond cross-linked antibacterial and adhesive hydrogel based on boronated chitosan derivative and loaded with peptides from Periplaneta americana with on-demand removability

The design and development of a bio-adhesive hydrogel with on-demand removability and excellent antibacterial activities are meaningful to achieve high wound closure effectiveness and post-wound-closure care, which is desirable in clinical applications. In this work, a series of adhesive antioxidant antibacterial hydrogels containing peptides from Periplaneta americana (PAP) were prepared through multi-dynamic-bond cross-linking among 3,4-dihydroxybenzaldehyde (DBA) containing catechol and aldehyde groups and chitosan grafted with 3-carboxy-4-fluorophenylboronic acid (CS-FPBA) to enable the effective adhesion of skin tissues and prevention of bacterial infection of wound. PAP was derived from alcohol-extracted residues generated during the pharmaceutical process, aiming to minimize resource wastage and achieve the high-value development of such a medicinal insect. The hydrogel was prepared by freezing-thawing with no toxic crosslinkers. The multi-dynamic-bond cross-linking of dynamic borate ester bonds and dynamic Schiff base bonds can achieve reversible breakage and re-formation and the adhesive strength of CS-FPBA-DBA-P-gel treated with a 20 % glucose solution dramatically decreased from 3.79 kPa to 0.35 kPa within 10 s. Additionally, the newly developed hydrogel presents ideal biocompatibility, hemostasis and antibacterial activity against Staphylococcus aureus and Escherichia coli compared to commercial chitosan gel (approximately 50 % higher inhibition rate), demonstrating its great potential in dealing with infected full-thickness skin wounds.

Effect of ‘Procumbenase’ a serine protease from Tridax procumbens aqueous extract on wound healing: A scar free healing of full thickness wounds

Wound healing involves several cellular and molecular pathways. Tridax procumbens activates genetic pathways with antibacterial, antioxidant, anticancer, and anti-inflammatory properties, aiding wound healing. This study purified Procumbenase, a serine protease from T. procumbens extract, using gel filtration (Sephadex G-75) and ion exchange (CM-Sephadex C-50) chromatography. Characterization involved analyses of protease activity, RP-HPLC, SDS-PAGE, gelatin zymogram, PAS staining, mass spectrometry, and circular dichroism. Optimal pH and temperature were determined. Protease type was identified using inhibitors. Wound-healing potential was evaluated through tensile strength, wound models, hydroxyproline estimation, and NIH 3T3 cell scratch analysis. In incision wound rat models, Procumbenase increased tensile strength on day 14 more than saline and Povidone‑iodine. It increased wound contraction by 89 % after 10 days in excision wound models, attaining full contraction by day 15 and closure by day 21. Scarless wound healing was enhanced by 18 days of epithelialization against 22 and 21 days for saline and povidone‑iodine. Procumbenase increased hydroxyproline concentration 2.53-fold (59.93 ± 2.89 mg/g) compared to saline (23.67 ± 1.86 mg/g). In NIH 3 T3 cell scratch assay, Procumbenase increased migration by 60.93 % (50 μg) and 60.57 % (150 μg) after 48 h. Thus, Procumbenase is the primary bioactive molecule in T. procumbens, demonstrates scar-free wound healing properties.

The mesenchymal stromal cell secretome promotes tissue regeneration and increases macrophage infiltration in acute and methicillin-resistant Staphylococcus aureus-infected skin wounds in vivo

Background aimsThe prevalence of chronic wounds continues to be a burden in human medicine. Methicillin-resistant Staphylococcus aureus (MRSA) is commonly isolated from infected wounds. MRSA infections primarily delay healing by impairing local immune cell functions. This study aimed to investigate the potential of mesenchymal stromal cell (MSC)-secreted bioactive factors, defined as the secretome, to improve innate immune responses in vivo. MSCs were isolated from the bone marrow of horses, which serve as valuable translational models for wound healing. The MSC secretome, collected as conditioned medium (CM), was evaluated in vivo using mouse models of acute and MRSA-infected skin wounds. MethodsPunch biopsies were used to create two full-thickness skin wounds on the back of each mouse. Acute wounds were treated daily with control medium or bone marrow-derived MSC (BM-MSC) CM. The antibiotic mupirocin was administered as a positive control for the MRSA-infected wound experiments. Wounds were photographed daily, and wound images were measured to determine the rate of closure. Trichrome staining was carried out to examine wound tissue histologically, and immunofluorescence antibody binding was used to assess immune cell infiltration. Wounds in the MRSA-infected model were swabbed for quantification of bacterial load. ResultsAcute wounds treated with BM-MSC CM showed accelerated wound closure compared with controls, as illustrated by enhanced granulation tissue formation and resolution, increased vasculature and regeneration of hair follicles. This treatment also led to increased neutrophil and macrophage infiltration. Chronic MRSA-infected wounds treated with BM-MSC CM showed reduced bacterial load accompanied by better resolution of granulation tissue formation and increased infiltration of pro-healing M2 macrophages compared with control-treated infected wounds. ConclusionsCollectively, our findings indicate that BM-MSC CM exerts pro-healing, immunomodulatory and anti-bacterial effects on wound healing in vivo, validating further exploration of the MSC secretome as a novel treatment option to improve healing of both acute and chronic wounds, especially those infected with antibiotic-resistant bacteria.

Tropoelastin modulates systemic and local tissue responses to enhance wound healing

Wound healing is facilitated by biomaterials-based grafts and substantially impacted by orchestrated inflammatory responses that are essential to the normal repair process. Tropoelastin (TE) based materials are known to shorten the period for wound repair but the mechanism of anti-inflammatory performance is not known. To explore this, we compared the performance of the gold standard Integra Dermal Regeneration Template (Integra), polyglycerol sebacate (PGS), and TE blended with PGS, in a murine full-thickness cutaneous wound healing study. Systemically, blending with TE favorably increased the F4/80+ macrophage population by day 7 in the spleen and contemporaneously induced elevated plasma levels of anti-inflammatory IL-10. In contrast, the PGS graft without TE prompted prolonged inflammation, as evidenced by splenomegaly and greater splenic granulocyte and monocyte fractions at day 14. Locally, the inclusion of TE in the graft led to increased anti-inflammatory M2 macrophages and CD4+T cells at the wound site, and a rise in Foxp3+ regulatory T cells in the wound bed by day 7. We conclude that the TE-incorporated skin graft delivers a pro-healing environment by modulating systemic and local tissue responses. Statement of significanceTropoelastin (TE) has shown significant benefits in promoting the repair and regeneration of damaged human tissues. In this study, we show that TE promotes an anti-inflammatory environment that facilitates cutaneous wound healing. In a mouse model, we find that inserting a TE-containing material into a full-thickness wound results in defined, pro-healing local and systemic tissue responses. These findings advance our understanding of TE's restorative value in tissue engineering and regenerative medicine, and pave the way for clinical applications.

A hydrogel based on Bletilla striata polysaccharide and hyaluronic acid topically administers tetramethylpyrazine for diabetic wound therapy

The delayed and incomplete wound healing often gives rise to the disability and mortality of diabetic patients. Conventional regimens are frequently inefficient to achieve diabetic wound recovery, and innovative alternatives are therefore needed to provide therapeutic benefits. Over the past decades, the advances in phytomedicines have revolutionized the field of wound healing and tissue regeneration. In the present study, tetramethylpyrazine (TMP), an alkaloid isolated from Ligusticum chuanxiong Hort, was applied for diabetic wound treatment. A hydrogel was developed using two biopolymers namely Bletilla striata polysaccharide (BSP) and hyaluronic acid (HA) for facilitating in situ administration of TMP on full-thickness wound in mice with streptozocin-induced diabetes. The resulting hydrogel formulation (termed TMP-BSP-HA) fulfilled inflammation attenuation, blood vessel growth, and collagen deposition. Consequently, TMP-BSP-HA significantly expedited diabetic wound healing relative to a TMP-loaded hydrogel formulation prepared by INTRASITE Gel (a commercial carboxymethylcellulose-based wound dressing). The present study demonstrates the pro-healing efficacy of TMP-BSP-HA, and provides a promising approach for diabetic wound therapy.

Accelerated full-thickness skin wound tissue regeneration by self-crosslinked chitosan hydrogel films reinforced by oxidized CNC-AgNPs stabilized Pickering emulsion for quercetin delivery

BackgroundThe non-toxic self-crosslinked hydrogel films designed from biocompatible materials allow for controlled drug release and have gathered remarkable attention from healthcare professionals as wound dressing materials. Thus, in the current study the chitosan (CS) film is infused with oil-in-water Pickering emulsion (PE) loaded with bioactive compound quercetin (Qu) and stabilized by dialdehyde cellulose nanocrystal-silver nanoparticles (DCNC-AgNPs). The DCNC-AgNPs play a dual role in stabilizing PE and are involved in the self-crosslinking with CS films. Also, this film could combine the advantage of the controlled release and synergistic wound-healing effect of Qu and AgNPs.ResultsThe DCNC-AgNPs were synthesized using sodium periodate oxidation of CNC. The DCNC-AgNPs were used to stabilize oil-in-water PE loaded with Qu in its oil phase by high speed homogenization. Stable PEs were prepared by 20% v/v oil: water ratio with maximum encapsulation of Qu in the oil phase. The Qu-loaded PE was then added to CS solution (50% v/v) to prepare self-crosslinked films (CS-PE-Qu). After grafting CS films with PE, the surface and cross-sectional SEM images show an inter-penetrated network within the matrix between DCNC and CS due to the formation of a Schiff base bond between the reactive aldehyde groups of DCNC-AgNPs and amino groups of CS. Further, the addition of glycerol influenced the extensibility, swelling ratio, and drug release of the films. The fabricated CS-PE-Qu films were analyzed for their wound healing and tissue regeneration potential using cell scratch assay and full-thickness excisional skin wound model in mice. The as-fabricated CS-PE-Qu films showed great biocompatibility, increased HaCat cell migration, and promoted collagen synthesis in HDFa cells. In addition, the CS-PE-Qu films exhibited non-hemolysis and improved wound closure rate in mice compared to CS, CS-Qu, and CS-blank PE. The H&E staining of the wounded skin tissue indicated the wounded tissue regeneration in CS-PE-Qu films treated mice.ConclusionResults obtained here confirm the wound healing benefits of CS-PE-Qu films and project them as promising biocompatible material and well suited for full-thickness wound healing in clinical applications.Graphical

Aloesin-loaded chitosan/cellulose-based scaffold promotes skin tissue regeneration

Skin wound healing and regeneration is very challenging across the world as simple or acute wounds can be transformed into chronic wounds or ulcers due to foreign body invasion, or diseases like diabetes or cancer. The study was designed to develop a novel bioactive scaffold, by loading aloesin to chitosan-coated cellulose scaffold, to cure full-thickness skin wounds. The physiochemical characterization of the scaffold was carried out using scanning electron microscopy (SEM) facilitated by energy-dispersive spectrophotometer (EDS), atomic force microscopy (AFM), and Fourier transform infrared spectroscopy (FTIR). The results indicated the successful coating of chitosan and aloesin on cellulose without any physical damage. The drug release kinetics confirmed the sustained release of aloesin by showing a cumulative release of up to 88 % over 24 h. The biocompatibility of the aloesin-loaded chitosan/cellulose (AlCsCFp) scaffold was evaluated by the WST-8 assay that confirmed the significantly increased adherence and proliferation of fibroblasts on the AlCsCFp scaffold. The in vivo wound healing study showed that both 0.05 % and 0.025 % AlCsCFp scaffolds have significantly higher wound closure rates (i.e. 88.2 % and 95.6 % approximately) as compared to other groups. This showed that novel composite scaffold has a wound healing ability. Furthermore, histological and gene expression analysis demonstrated that the scaffold also induced cell migration, angiogenesis, re-epithelialization, collagen deposition, and tissue granulation formation. Thus, it is concluded that the aloesin-loaded chitosan/cellulose-based scaffold has great therapeutic potential for being used in wound healing applications in the clinical setting in the future.

A Novel Dehydrated Human Umbilical Cord Particulate Medical Device: Matrix Characterization, Performance, and Biocompatibility for the Management of Acute and Chronic Wounds.

Chronic wounds present a significant socioeconomic burden forecasted to increase in prevalence and cost. Minimally manipulated human placental tissues have been increasingly employed and proven to be advantageous in the treatment of chronic wounds, showing improved clinical outcomes and cost-effectiveness. However, technological advances have been constrained by minimal manipulation and homologous use criteria. This study focuses on the characterization of a novel dehydrated human umbilical cord particulate (dHUCP) medical device, which offers a unique allogeneic technological advancement and the first human birth tissue device for wound management. Characterization analyses illustrated a complex extracellular matrix composition conserved in the dHUCP device compared to native umbilical cord, with abundant collagens and glycosaminoglycans imbibing an intricate porous scaffold. Dermal fibroblasts readily attached to the intact scaffold of the dHUCP device. Furthermore, the dHUCP device elicited a significant paracrine proliferative response in dermal fibroblasts, in contrast to fibrillar collagen, a prevalent wound device. Biocompatibility testing in a porcine full-thickness wound model showed resorption of the dHUCP device and normal granulation tissue maturation during healing. The dHUCP device is a promising advancement in wound management biomaterials, offering a unique combination of structural complexity adept for challenging wound topographies and a microenvironment supportive of tissue regeneration.

Aggregation-Induced Emission Photosensitizer with Ag(I)-π Interaction-Enhanced Reactive Oxygen Species for Eliminating Multidrug Resistant Bacteria.

Multidrug-resistant (MDR) bacteria pose serious threats to public health due to the lack of effective and biocompatible drugs to kill MDR bacteria. Photodynamic antibacterial therapy has been widely studied due to its low induction of resistance. However, photosensitizers that can efficiently generate reactive oxygen species (ROS) through both type I and type II mechanisms and that have the capability of multiple modes of action are rarely reported. Addressing this issue, we developed a near-infrared-emitting triphenylamine indole iodoethane (TTII) and its silver(I) self-assembled (TTIIS) aggregation-induced emission (AIE) photosensitizer for multimode bacterial infection therapy. TTII can efficiently produce both Type I ROS •OH and Type II ROS 1O2. Interestingly, the Ag(I)-π interaction contributed in TTIIS efficiency promotion of the generation of 1O2. Moreover, by releasing Ag+, TTIIS enabled photodynamic-Ag(I) dual-mode sterilization. As a result, TTIIS achieved an effective enhancement of antibacterial activity, with a 1-2-fold boost against multidrug-resistant Escherichia coli (MDR E. coli). Both TTII and TTIIS at a concentration as low as 0.55 μg mL-1 can kill more than 98% of methicillin resistant Staphylococcus aureus (MRSA) on MRSA-infected full-thickness defect wounds of a mouse, and both TTII and TTIIS were effective in eliminating the bacteria and promoting wound healing.

Self-Healing Conductive Hydrogels with Dynamic Dual Network Structure Accelerate Infected Wound Healing via Photothermal Antimicrobial and Regulating Inflammatory Response.

Wound infections are an escalating clinical challenge with continuous inflammatory response and the threat of drug-resistant bacteria. Herein, a series of self-healing conductive hydrogels were designed based on carboxymethyl chitosan/oxidized sodium alginate/polymerized gallic acid/Fe3+ (CMC/OSA/pGA/Fe3+, COGFe) for promoting infected wound healing. The Schiff base and catechol-Fe3+ chelation in the dynamical dual network structure of the hydrogels endowed dressings with good toughness, conductivity, adhesion, and self-healing properties, thus flexibly adapting to the deformation of skin wounds. In terms of ultraviolet (UV) resistance and scavenging of reactive oxygen species (ROS), the hydrogels significantly reduced oxidative stress at the wound site. Additionally, the hydrogels with photothermal therapy (PTT) achieved a 95% bactericidal rate in 5 min of near-infrared (NIR) light radiation by disrupting the bacterial cell membrane structure through elevated temperature. Meanwhile, the inherent antimicrobial properties of GA could reduce healthy tissue damage caused by excessive heat. The composite hydrogels could effectively promote the proliferation and migration of fibroblasts and possess good biocompatibility and hemostatic effect. In full-thickness infected wound repair experiments in rats, the COGFe5 hydrogel combined with NIR effectively killed bacteria, modulated macrophage polarization (M1 to M2 phenotype) to improve the immune microenvironment of the wound, and shortened the repair time by accelerating the expression of collagen deposition (TGF-β) and vascular factors (CD31). This combined therapy might provide a prospective strategy for infectious wound treatment.

Facile Synthesis of Multifunctional Mesoporous Starch-Based Microparticle for Effective Hemostasis and Wound Healing.

Uncontrolled hemorrhage and infection are the principal causes of mortality associated with trauma in both military and civilian medical settings. Modified starch granules have emerged as a safe hemostatic agent for irregular and noncompressible wounds, but their performance is constrained by limited hemostasis efficiency and modest antibacterial activity. This study reported a directed self-assembly approach for a multifunctional mesoporous starch-based microparticle loaded with chitosan and calcium ions (Ca@MSMP) used for rapid hemostasis and wound healing. Directed self-assembly of uniform Ca@MSMP with a hierarchical hollow structure in the presence of chitosan was confirmed by scanning electron microscopy (SEM) analysis and pore structure analysis. The resulting Ca@MSMP exhibited a well-defined spherical shape and uniform size of 1 μm and demonstrated excellent antibacterial activity (>95%) without hemolytic activity. Importantly, Ca@MSMP enhanced blood coagulation and platelet aggregation via the synergistic effect of rapid calcium release and chitosan-mediated electrostatic interactions, leading to a significant decrease in blood loss and reduction in hemostasis time in rat tail amputation and liver injury models. In comparative analyses, Ca@MSMP significantly outperformed the commercial hemostatic agent Quickclean, notably enhancing the healing of full-thickness skin wounds in vivo by effectively preventing infection. These results underscore the potential of this innovative hemostatic material in diverse clinical scenarios, offering effective solutions for the management of bleeding in wounds that are irregularly shaped and noncompressible.