Functional Hydrogels as Wound Dressing to Enhance Wound Healing.
ACS nano
Hydrogels, due to their excellent biochemical and mechnical property, have shown attractive advantages in the field of wound dressings. However, a comprehensive review of the functional hydrogel as a wound dressing is still lacking. This work first summarizes the skin wound healing process and relates evaluation parameters and then reviews the advanced functions of hydrogel dressings such as antimicrobial property, adhesion and hemostasis, anti-inflammatory and anti-oxidation, substance delivery, self-healing, stimulus response, conductivity, and the recently emerged wound monitoring feature, and the strategies adopted to achieve these functions are all classified and discussed. Furthermore, applications of hydrogel wound dressing for the treatment of different types of wounds such as incisional wound and the excisional wound are summarized. Chronic wounds are also mentioned, and the focus of attention on infected wounds, burn wounds, and diabetic wounds is discussed. Finally, the future directions of hydrogel wound dressings for wound healing are further proposed.
10.1021/acsnano.1c04206
Anti-Inflammatory Peptide-Conjugated Silk Fibroin/Cryogel Hybrid Dual Fiber Scaffold with Hierarchical Structure Promotes Healing of Chronic Wounds.
Advanced materials (Deerfield Beach, Fla.)
Chronic wounds resulting from diabetes, pressure, radiation therapy, and other factors continue to pose significant challenges in wound healing. To address this, this study introduces a novel hybrid fibroin fibrous scaffold (FFS) comprising randomly arranged fibroin fibers and vertically aligned cryogel fibers (CFs). The fibroin scaffold is efficiently degummed at room temperature and simultaneously formed a porous structure. The aligned CFs are produced via directional freeze-drying, achieved by controlling solution concentration and freezing polymerization temperature. The incorporation of aligned CFs into the expanded fibroin fiber scaffold leads to enhanced cell infiltration both in vitro and in vivo, further elevating the hybrid scaffold's tissue compatibility. The anti-inflammatory peptide 1 (AP-1) is also conjugated to the hybrid fibrous scaffold, effectively transforming the inflammatory status of chronic wounds from pro-inflammatory to pro-reparative. Consequently, the FFS-AP1+CF group demonstrates superior granulation tissue formation, angiogenesis, collagen deposition, and re-epithelialization during the proliferative phase compared to the commercial product PELNAC. Moreover, the FFS-AP1+CF group displays epidermis thickness, number of regenerated hair follicles, and collagen density closer to normal skin tissue. These findings highlight the potential of random fibroin fibers/aligned CFs hybrid fibrous scaffold as a promising approach for skin tissue filling and tissue regeneration.
10.1002/adma.202307328
Exudate Absorbing and Antimicrobial Hydrogel Integrated with Multifunctional Curcumin-Loaded Magnesium Polyphenol Network for Facilitating Burn Wound Healing.
ACS nano
Burns are among the most common causes of trauma worldwide. Reducing the healing time of deep burn wounds has always been a major challenge. Traditional dressings not only require a lengthy medical procedure but also cause unbearable pain and secondary damage to patients. In this study, we developed an exudate-absorbing and antimicrobial hydrogel with a curcumin-loaded magnesium polyphenol network (Cur-Mg@PP) to promote burn wound healing. That hydrogel was composed of an ε-poly-l-lysine (ε-PLL)/polymer poly(γ-glutamic acid) (γ-PGA) hydrogel (PP) and curcumin-loaded magnesium polyphenol network (Cur-Mg). Because of the strong water absorption property of ε-PLL and γ-PGA, Cur-Mg@PP powder can quickly absorb the wound exudate and transform into a moist and viscous hydrogel, thus releasing payloads such as magnesium ion (Mg) and curcumin (Cur). The released Mg and Cur demonstrated good therapeutic efficacy on analgesic, antioxidant, anti-inflammation, angiogenesis, and tissue regeneration. Our findings provide a strategy for accelerating burn wound healing.
10.1021/acsnano.3c04556
Early prevention of trauma-related infection/sepsis.
Ma Xiao-Yuan,Tian Li-Xing,Liang Hua-Ping
Military Medical Research
Trauma still represents one of the major causes of death worldwide. Despite the reduction of post-traumatic sepsis over the past two decades, the mortality of septic trauma inpatients is still high (19.5-23 %). Early prevention of sepsis development can aid in the subsequent treatment of patients and help improve their outcomes. To date, the prevention of trauma-related infection/sepsis has mainly included infection prevention (e.g., surgical management, prophylactic antibiotics, tetanus vaccination, immunomodulatory interventions) and organ dysfunction prevention (e.g., pharmaceuticals, temporary intravascular shunts, lung-protective strategies, enteral immunonutrition, acupuncture). Overall, more efficient ways should be developed to prevent trauma-related infection/sepsis.
10.1186/s40779-016-0104-3
Cryogel/hydrogel biomaterials and acupuncture combined to promote diabetic skin wound healing through immunomodulation.
Chen Tsai-Yu,Wen Tsung-Kai,Dai Niann-Tzyy,Hsu Shan-Hui
Biomaterials
Unhealed chronic wounds often deteriorate into multiple infection with several kinds of bacteria and excessive proteolytic wound exudate and remains one of the common healthcare issues. Here, the functional and antimicrobial hydrogel and cryogel biomaterials were prepared from glycol chitosan and a novel biodegradable Schiff base crosslinker difunctional polyurethane (DF-PU). The cryogel exhibited ~2730 ± 400% of water absorption with abundant macropores and 86.5 ± 1.6% of porosity formed by ice crystal as well as ~240% cell proliferation effect; while the hydrogel demonstrated considerable antimicrobial activity and biodegradability. As an optimized procedure to treat the diabetic skin wound in a rat model, the combined application of adipose stem cell-seeded cryogel/hydrogel biomaterials on the wound and acupuncture surrounding the wound may attain 90.34 ± 2.3% of wound closure and secure the formation of granulation tissue with sufficient microvessels and complete re-epithelialization in 8 days. The average increases in the superficial temperature of wounded animals after acupuncture were about 1-2 °C. Through the activation of C3a and C5a, the increased secretion of cytokines SDF-1 and TGFβ-1, as well as the down-regulation of proinflammatory cytokines TNF-α and IL-1β, the combined treatment of stem cell-seeded cryogel/hydrogel biomaterials and acupuncture on wounds produced synergistic immunomodulatory effects. The strategy using the combined treatment of biomaterials, stem cells, and acupuncture reveals a perspective new approach to accelerate the tissue regeneration.
10.1016/j.biomaterials.2020.120608
[Advances in the research of the relationship between wound temperature and wound healing].
Zhu L Y,Guo S X,Wu P,Li Q,Ho Z J,Yu M R,Weng T T,Han C M
Zhonghua shao shang za zhi = Zhonghua shaoshang zazhi = Chinese journal of burns
There are many factors that may affect the microenvironment of acute and chronic wounds. This article reviews the relationship between temperature factor in the external microenvironment of wound surface and wound healing. The temperature changes in different types and stages of wounds are closely related to the wound healing status. Therefore, wound temperature monitoring provides timely, reliable, and non-invasive method in the evaluation of wound status. As low temperature affects the physiological state of wound, relieving the low temperature state and maintaining normal temperature of the microenvironment of wound can promote wound healing. Further research is needed on the wound repair related effector cell proliferation and the mechanism of regulatory function to determine the optimal constant temperature and heat treatment duration needed for wound healing.
10.3760/cma.j.issn.1009-2587.2018.11.021
[The modern approach to wound treatment].
Komarcević A
Medicinski pregled
INTRODUCTION:Wound healing is a complex process involving interactions among a variety of different cell types. The normal wound repair process consists of three phases--inflammation, proliferation, and remodeling that occur in a predictable series of cellular and biochemical events. Wounds are classified according to various criteria: etiology, lasting, morphological characteristics, communications with solid or hollow organs, the degree of contamination. In the last few years many authors use the Color Code Concept, which classifies wounds as red, yellow and black wounds. This paper presents conventional methods of local wound treatment (mechanical cleansing, disinfection with antiseptic solutions, wound debridement--surgical, biological and autolytic; wound closure, topical antibiotic treatment, dressing), as well as general measures (sedation, antitetanous and antibiotic protection, preoperative evaluation and correction of malnutrition, vasoconstriction, hyperglycemia and steroid use, appropriate surgical technique, and postoperative prevention of vasoconstriction through pain relief, warming and adequate volume resuscitation). THE ROLE OF PHYSIOLOGICAL FACTORS AND ANTIMICROBIAL AGENTS IN WOUND HEALING:Growth factors play a role in cell division, migration, differentiation, protein expression, enzyme production and have a potential ability to heal wounds by stimulating angiogenesis and cellular proliferation, affecting the production and the degradation of the extracellular matrix, and by being chemotactic for inflammatory cells and fibroblasts. There are seven major families of growth factors: epidermal growth factor (EGF), transforming growth factor-beta (TGF-beta), insulin-like growth factor (IGF), platelet-derived growth factor (PDGF), fibroblast growth factor (FGF), interleukins (ILs), and colony-stimulating factor (CSF). Acute wounds contain many growth factors that play a crucial role in the initial phases of wound healing. The events of early wound healing reflect a finely balanced environment leading to uncomplicated and rapid wound healing. Chronic wounds, for many reasons, have lost this fine balance. Multiple studies have evaluated the effect that exogenously applied growth factors have on the healing of chronic wounds. In the study conducted by Knighton and colleagues, topical application of mixture of various growth factors (PDGF, TGF-beta, PDAF, PF4, PDEGF) demonstrated increased wound healing over controls. Brown and associates demonstrated a decrease in skin graft donor site healing time of 1 day using topically applied EGF. Herndon and ass. used systemic growth hormone in burned children and reduction in healing time made a significant clinical difference by allowing earlier wound coverage and decreasing the duration of hospitalization. The TGF family of growth factors is believed to be primarily responsible for excessive scar formation, especially the beta 1 and beta 2 isoforms. TGF-beta 3 isoform has recently been described and may have an inhibitory function on scar formation by being a natural antagonist to the TGF-beta 1 and TGF-beta 2 isoforms. Cytokines, especially interferon-alpha (INF-alpha), INF-alpha, and INF-alpha 2b, may also reduce scar formation. These cytokines decrease the proliferation rate of fibroblasts and reduce the rate of collagen and fibronectin synthesis by reducing the production of mRNA. Expression of nitric oxide synthase (NOS) and heat shock proteins (HSP) have an important role in wound healing, as well as trace elements (zinc, copper, manganese). Applications of some drugs (antioxidants--asiaticoside, vitamin E and ascorbic acid; calcium D-pantothenate, exogenous fibronectin; antileprosy drugs--oil of hydnocarpus; alcoholic extract of yeast) accelerate wound healing. Thymic peptide thymosin beta 4 (T beta 4R) topically applicated, increases collagen deposition and angiogenesis and stimulates keratinocyte migration. Thymosin alpha 1 (T alpha 1R), peptide isolated from the thymus, is a potent chemoattractant which accelerates angiogenesis and wound healing. On the contrary, steroid drugs, hemorrhage and denervation of wounds have negative effect on the healing process.
Local Immunomodulation Using an Adhesive Hydrogel Loaded with miRNA-Laden Nanoparticles Promotes Wound Healing.
Small (Weinheim an der Bergstrasse, Germany)
Chronic wounds are characterized by impaired healing and uncontrolled inflammation, which compromise the protective role of the immune system and may lead to bacterial infection. Upregulation of miR-223 microRNAs (miRNAs) shows driving of the polarization of macrophages toward the anti-inflammatory (M2) phenotype, which could aid in the acceleration of wound healing. However, local-targeted delivery of microRNAs is still challenging, due to their low stability. Here, adhesive hydrogels containing miR-223 5p mimic (miR-223*) loaded hyaluronic acid nanoparticles are developed to control tissue macrophages polarization during wound healing processes. In vitro upregulation of miR-223* in J774A.1 macrophages demonstrates increased expression of the anti-inflammatory gene Arg-1 and a decrease in proinflammatory markers, including TNF-α, IL-1β, and IL-6. The therapeutic potential of miR-223* loaded adhesive hydrogels is also evaluated in vivo. The adhesive hydrogels could adhere to and cover the wounds during the healing process in an acute excisional wound model. Histological evaluation and quantitative polymerase chain reaction (qPCR) analysis show that local delivery of miR-223* efficiently promotes the formation of uniform vascularized skin at the wound site, which is mainly due to the polarization of macrophages to the M2 phenotype. Overall, this study demonstrates the potential of nanoparticle-laden hydrogels conveying miRNA-223* to accelerate wound healing.
10.1002/smll.201902232
Nanomedicines and gene therapy for the delivery of growth factors to improve perfusion and oxygenation in wound healing.
Desmet Céline M,Préat Véronique,Gallez Bernard
Advanced drug delivery reviews
Oxygen plays a key role in wound healing, and hypoxia is a major cause of wound healing impairment; therefore, treatments to improve hemodynamics and increase wound oxygenation are of particular interest for the treatment of chronic wounds. This article describes the roles of oxygen and angiogenesis in wound healing as well as the tools used to evaluate tissue oxygenation and perfusion and then presents a review of nanomedicines and gene therapies designed to improve perfusion and oxygenation and accelerate wound healing.
10.1016/j.addr.2018.02.001
Injury-activated glial cells promote wound healing of the adult skin in mice.
Parfejevs Vadims,Debbache Julien,Shakhova Olga,Schaefer Simon M,Glausch Mareen,Wegner Michael,Suter Ueli,Riekstina Una,Werner Sabine,Sommer Lukas
Nature communications
Cutaneous wound healing is a complex process that aims to re-establish the original structure of the skin and its functions. Among other disorders, peripheral neuropathies are known to severely impair wound healing capabilities of the skin, revealing the importance of skin innervation for proper repair. Here, we report that peripheral glia are crucially involved in this process. Using a mouse model of wound healing, combined with in vivo fate mapping, we show that injury activates peripheral glia by promoting de-differentiation, cell-cycle re-entry and dissemination of the cells into the wound bed. Moreover, injury-activated glia upregulate the expression of many secreted factors previously associated with wound healing and promote myofibroblast differentiation by paracrine modulation of TGF-β signalling. Accordingly, depletion of these cells impairs epithelial proliferation and wound closure through contraction, while their expansion promotes myofibroblast formation. Thus, injury-activated glia and/or their secretome might have therapeutic potential in human wound healing disorders.
10.1038/s41467-017-01488-2
Drug therapies and delivery mechanisms to treat perturbed skin wound healing.
Chin Jiah Shin,Madden Leigh,Chew Sing Yian,Becker David L
Advanced drug delivery reviews
Acute wound healing is an orderly process of four overlapping events: haemostasis, inflammation, proliferation and remodelling. A drug delivery system with a temporal control of release could promote each of these events sequentially. However, acute wound healing normally proceeds very well in healthy individuals and there is little need to promote it. In the elderly and diabetics however, healing is often slow and wounds can become chronic and we need to promote their healing. Targeting the events of acute wound healing would not be appropriate for a chronic wound, which have stalled in the proinflammatory phase. They also have many additional problems such as poor circulation, low oxygen, high levels of leukocytes, high reactive oxygen species, high levels of proteolytic enzymes, high levels of proinflammatory cytokines, bacterial infection and high pH. The future challenge will be to tackle each of these negative factors to create a wound environment conducive to healing.
10.1016/j.addr.2019.03.006
Circadian actin dynamics drive rhythmic fibroblast mobilization during wound healing.
Hoyle Nathaniel P,Seinkmane Estere,Putker Marrit,Feeney Kevin A,Krogager Toke P,Chesham Johanna E,Bray Liam K,Thomas Justyn M,Dunn Ken,Blaikley John,O'Neill John S
Science translational medicine
Fibroblasts are primary cellular protagonists of wound healing. They also exhibit circadian timekeeping, which imparts an approximately 24-hour rhythm to their biological function. We interrogated the functional consequences of the cell-autonomous clockwork in fibroblasts using a proteome-wide screen for rhythmically expressed proteins. We observed temporal coordination of actin regulators that drives cell-intrinsic rhythms in actin dynamics. In consequence, the cellular clock modulates the efficiency of actin-dependent processes such as cell migration and adhesion, which ultimately affect the efficacy of wound healing. Accordingly, skin wounds incurred during a mouse's active phase exhibited increased fibroblast invasion in vivo and ex vivo, as well as in cultured fibroblasts and keratinocytes. Our experimental results correlate with the observation that the time of injury significantly affects healing after burns in humans, with daytime wounds healing ~60% faster than nighttime wounds. We suggest that circadian regulation of the cytoskeleton influences wound-healing efficacy from the cellular to the organismal scale.
10.1126/scitranslmed.aal2774
Skin Cell Heterogeneity in Development, Wound Healing, and Cancer.
Trends in cell biology
Skin architecture and function depend on diverse populations of epidermal cells and dermal fibroblasts. Reciprocal communication between the epidermis and dermis plays a key role in skin development, homeostasis and repair. While several stem cell populations have been identified in the epidermis with distinct locations and functions, it is now recognised that there is additional heterogeneity within the mesenchymal cells of the dermis. Here, we discuss recent insights into how these distinct cell populations are maintained and coordinated during development, homeostasis, and wound healing. We highlight the importance of the local environment, or niche, in cellular plasticity. We also discuss new mechanisms that have been identified as influencing wound repair and cancer progression.
10.1016/j.tcb.2018.05.002
The Evolution of Animal Models in Wound Healing Research: 1993-2017.
Parnell Laura K S,Volk Susan W
Advances in wound care
Wound healing is a complex and dynamic series of events influenced by a variety of intrinsic and extrinsic factors. Problematic wounds, particularly chronic wounds and pathologic scars, remain clinically significant burdens. Modeling physiologic and aberrant wound repair processes using or models have contributed to (); however, the fidelity of each model used, particularly with respect to its species-specific limitations, must be taken into account for extrapolation to human patients. Twenty-five years of wound healing models published in (1993-2017) and (2012-2017) were collected and analyzed to determine trends in species utilization and models used. In 25 years, 1,521 original research articles utilizing one or more wound models were published (total of 1,665 models). Although 20 different species were used over the course of 25 years, 5 species were most commonly utilized: human, mouse, rat, pig, and rabbit. modeling was used most frequently, followed by , , and modeling of wound healing processes. A comparison of articles from 1993 to 1997 and 2013 to 2017 periods showed notable differences in model and species usage. Experiments utilizing mouse and human models increased, while the usage of pig models remained constant, rabbit and rat models declined in the more recent time period examined compared to the time period two decades before. This analysis shows notable changes in types of models and species used over time which may be attributed to new knowledge, techniques, technology, and/or reagents. Explorations into mechanisms of limb regeneration and wound healing of noncutaneous tissues have also contributed to a shift in modeling over time. Changes within the journals (, page expansion and increased rejection rates), research funding, and model expense may also influence the observed shifts.
10.1089/wound.2019.1098
Cellular and molecular mechanisms of repair in acute and chronic wound healing.
Martin P,Nunan R
The British journal of dermatology
A considerable understanding of the fundamental cellular and molecular mechanisms underpinning healthy acute wound healing has been gleaned from studying various animal models, and we are now unravelling the mechanisms that lead to chronic wounds and pathological healing including fibrosis. A small cut will normally heal in days through tight orchestration of cell migration and appropriate levels of inflammation, innervation and angiogenesis. Major surgeries may take several weeks to heal and leave behind a noticeable scar. At the extreme end, chronic wounds - defined as a barrier defect that has not healed in 3 months - have become a major therapeutic challenge throughout the Western world and will only increase as our populations advance in age, and with the increasing incidence of diabetes, obesity and vascular disorders. Here we describe the clinical problems and how, through better dialogue between basic researchers and clinicians, we may extend our current knowledge to enable the development of novel potential therapeutic treatments.
10.1111/bjd.13954
Diversity of Fibroblasts and Their Roles in Wound Healing.
Cold Spring Harbor perspectives in biology
Wound healing disorders are a societal, clinical, and healthcare burden and understanding and treating them is a major challenge. A particularly important cell type in the wound healing processes is the fibroblast. Fibroblasts are not homogenous; however, there are diverse functional fibroblast subtypes coming from different embryonic origins and residing in dispersed anatomic locations including distinct classes of fibroblasts at various skin depths. In this review, we discuss the implications of fibroblast heterogeneity, with a focus on the fundamental physiological functions of the fibroblast subtypes that govern wound repair and clinical degrees of healing. A better understanding of these diverse functional fibroblast populations will likely lead to novel therapies to enhance wound healing and inhibit excessive scarring.
10.1101/cshperspect.a041222