Course Of Wound Healing Research Articles

Clinical course of wound healing in patients with odontogenic phlegmons of the maxillofacial area with concomitant liver pathology

Clinical course of wound healing in patients with odontogenic phlegmons of the maxillofacial area with concomitant liver pathology

Botulinum toxin in wound treatment – literature review

Introduction and purpose Botulinum toxin has been used in medicine since the 1970s, although many years earlier it was known only as a biological weapon. Originally, it was used in medicine to treat strabismus in children. Over time, it has been used in the treatment of neurological disorders, excessive sweating of the armpits, wrinkles, and bladder disorders. In recent years, botulinum toxin has also begun to be used in wound healing. The paralyzing effect of botulinum toxin on the muscles within the wound eliminates micro-injuries caused by tension in these muscles. The aim of the article is to summarize information on the effects of botulinum toxin on the wound, its impact on inflammation, and the type of scar formation. Materials and methods The literature included in the PubMed databases is searched through the words such as botulinum toxin, wounds, and scars. Description of the state of knowledge: The literature review shows the breadth of the issue. Scientific studies showing the effect of using botulinum toxin on wounds emphasize its beneficial effects. However, it should be remembered that wound healing has a complex, dynamic course supported by numerous cellular processes that must be closely coordinated to effectively repair damaged tissues. Determinants influencing the course of wound healing include both local and systemic factors. Important factors influencing the process of proper wound healing are specialized wound preparation, pharmacotherapy, and other aspects of therapeutic intervention. Conclusions The range of applications of botulinum toxin is constantly expanding. In addition to reducing muscle tension within the wound, it also inhibits the production of inflammatory transmitters, limiting its development, and also reduces the development of microcirculation by preventing the development of vessels in hypertrophic scars.

Management of biofilm-associated infections in diabetic wounds – from bench to bedside

Abstract Biofilms are complex bacterial colonies embedded in an extracellular matrix. These pose a major obstacle to wound healing and are noticeable in chronic wounds. It protects the bacteria from the host’s immune system and conventional antibiotic treatments. The biofilm’s protective matrix prevents essential nutrients and oxygen from diffusing into the surrounding healthy tissue. In addition, microbes living in biofilms naturally have increased resistance to antibiotics, which reduces the effectiveness of traditional therapies. As such, biofilms serve as persistent reservoirs of infection, which further disrupts the normal course of wound healing. In this review, the current formulation strategies such as hydrogels, polymeric nanoparticles, and nanofibers that are used in wound healing to counteract biofilms have been comprehensively discussed. The formulations have been meticulously designed and developed to disturb the biofilm matrix, prevent the growth of microorganisms, and increase the potency of antimicrobials and antibiotics. The mechanism of action, advantages and limitations associated with the existing formulation strategies have been reviewed. The formulation strategies that have been translated into clinical applications and patented are also discussed in this paper.

Nanoliposome enabled topical gel-based drug delivery system of ivermectin: Fabrication, characterization, in vivo and in vitro investigation

Nanoliposomes loaded with ivermectin possess the ability to deliver the drug to an intended area, ensuring optimal stability and eventual release at that precise location. The nanoliposome's size range results in an expanded surface area, which enables the delivery of the maximum amount of medication to the designed location. This investigation shows that the thin film lipid hydration technique can be employed to formulate nanoliposomes. For the formulation, the amount of cholesterol and phosphatidylcholine was chosen applying response surface methodology (RSM). With a range of zeta potentials from −13.4 ​± ​0.14 ​mV to −34.5 ​± ​0.11 ​mV, average dimension of the particles in the different formulation tested in this study is between 93.2 ​nm and 156.4 ​nm. The factorial design optimization demonstrates that the entrapment efficiency (Y3) has a p-value of 0.0160, the percentage of medicament release rate 8 ​h (Y1) has a p-value of 0.0414, and the percentage of medicament release rate 12 ​h (Y2) has a p-value of 0.0119. Therefore, all the models and responses were significant. After the thorough assessment from the present investigation, it was found that F7 batch has the highest R2 value and n exponent, the release kinetics of the ivermectin-loaded nanoliposome accompanied zero-order release model as well as korsmeyer–peppas model. Additionally, the current study demonstrated the histopathological assessments in the course of wound healing in animal model. Investigated results showcased that the ivermectin loaded nanoliposomes has substantial possibility as a nano conveyor for the targeted drug delivery system.

Achieving Clearance of Drug-Resistant Bacterial Infection and Rapid Cutaneous Wound Regeneration Using an ROS-Balancing-Engineered Heterojunction.

Intractable infected microenvironments caused by drug-resistant bacteria stalls the normal course of wound healing. Sono-piezodynamic therapy (SPT) is harnessed to combat pathogenic bacteria, but the superabundant reactive oxygen species (ROS) generated during SPT inevitably provoke severe inflammatory response, hindering tissue regeneration. Consequently, an intelligent nanocatalytic membrane composed of poly(lactic-co-glycolic acid) (PLGA) and black phosphorus /V2C MXene bio-heterojunctions (2D2-bioHJs) is devised. Under ultrasonication, 2D2-bioHJs effectively eliminate drug-resistant bacteria by disrupting metabolism and electron transport chain (ETC). When ultrasonication ceases, they enable the elimination of SPT-generated ROS. The 2D2-bioHJs act as a "lever" that effectively achieves a balance between ROS generation and annihilation, delivering both antibacterial and anti-inflammatory properties to the engineered membrane. More importantly, in vivo assays corroborate that the nanocatalytic membranes transform the stalled chronic wound environment into a regenerative one by eradicating the bacterial population, dampening the NF-κB inflammatory pathway and promoting angiogenesis. As envisaged, this work demonstrates a novel tactic to arm membranes with programmed antibacterial and anti-inflammatory effects to remedy refractory infected wounds from drug-fast bacteria.

Wound healing after therapy of oral potentially malignant disorders with a 445-nm semiconductor laser: a randomized clinical trial

ObjectivesOral potentially malignant disorders (OPMDs) are the most clinically relevant precursor lesions of the oral squamous cell carcinoma (OSCC). OSCC is one of the 15 most common cancers worldwide. OSCC is with its high rate of mortality an important cause of death worldwide. The diagnosis and therapy of clinically relevant precursor lesions of the OSCC is one of the main parts of prevention of this malignant disease. Targeted therapy is one of the main challenges concerning an oncologically safe tissue removal without overwhelming functional and aesthetic impairment.Materials and methodsIn this randomized controlled trial, a newly introduced intraoral 445-nm semiconductor laser (2W; cw-mode; SIROLaser Blue, Dentsply Sirona, Bensheim, Germany) was used in the therapy of OPMDs. Duration and course of wound healing, pain, and scar tissue formation were compared to classical cold blade removal with primary suture by measuring remaining wound area, tissue colorimetry, and visual analogue scale. The study includes 40 patients randomized using a random spreadsheet sequence in two groups (n1 = 20; n2 = 20).ResultsThis comparative analysis revealed a significantly reduced remaining wound area after 1, 2, and 4 weeks in the laser group compared to the cold blade group (p < 0.05). In the laser group, a significantly reduced postoperative pain after 1 week was measured (p < 0.05).ConclusionLaser coagulation of OPMDs with the investigated 445-nm semiconductor laser is a safe, gentle, and predictable surgical procedure with beneficial wound healing and reduced postoperative discomfort.Clinical relevanceCompared to the more invasive and bloody cold blade removal with scalpel, the 445-nm semiconductor laser could be a new functional less traumatic tool in the therapy of OPMDs. The method should be further investigated with regard to the identification of further possible indications.Trail registrationGerman Clinical Trials Register No: DRKS00032626.

507-P: Trajectories of Inflammatory Proteins over Diabetic Wound Healing Course

Background: Inflammatory processes are dynamic over the Diabetic Foot Ulceration (DFU) course. We aimed to evaluate longitudinal trajectories of circulating biomarkers in subjects with DFU. Methods: The study cohort comprised 39 subjects with DFU from the Joslin-Beth Israel Deaconess Foot Center. During the 12 weeks of follow-up (6 bi-weekly visits), 15 subjects (38%) had their DFU healed (healers). Twenty-eight proteins were measured at each visit on the Luminex platform. Results: Circulating IL-10 levels at baseline were significantly higher in DFU healers in comparison with non-healers (OR: 2.4, p=0.047). Moreover, IL-10 levels remained stable over time within each group (IL10 Δ in DFU healers: p=0.2 and in non-healers: p=0.8). Levels of 6 other proteins revealed dynamic trajectories over time in one or both groups: MMP-2, EGF, IFNγ, TNF, IL-8, and MIP1b. MMP-2 levels in healers increased from baseline to V6 (β=0.07, p=0.0003), but remained stable in non-healers. Conclusion: We identified an anti-inflammatory cytokine, IL-10, as a prognostic biomarker of the diabetic wound healing course. Six inflammatory proteins (MMP-2, EGF, IFNγ, TNF, IL-8, and MIP1b) revealed dynamic temporal changes in levels within or across groups. Disclosure S.Pickett: None. S.Moon: None. G.Theocharidis: None. Z.Md dom: None. M.Niewczas: None. A.Veves: None. Funding National Institutes of Health (R61DK131915, R01DK091949); Joslin Diabetes Center; National Rongxiang Xu Foundation

Application of combined photobiomodulation and curcumin-loaded iron oxide nanoparticles considerably enhanced repair in an infected, delayed-repair wound model in diabetic rats compared to either treatment alone.

Herein, we attempted toevaluate the therapeutic potential of photobiomodulation (PBM) and curcumin-loaded iron nanoparticles (CUR), alone and in combination, on wound closure rate (WCR), microbial flora by measuring colony-forming units (CFUs), the stereological and biomechanical properties of repairing wounds in the maturation stage of the wound healing course in an ischemic infected delayed healing wound model (IIDHWM) of type I diabetic (TIDM) rats. There were four groups: group 1 was the control, group 2 received CUR, rats in group 3 were exposed to PBM (80Hz, 890nm, and 0.2J/cm2), and rats in group 4 received both PBM and CUR (PBM + CUR). We found CFU was decreased in groups 2, 3, and 4 compared to group 1 (p = 0.000 for all). Groups 2, 3, and 4 showed a considerable escalation in WCR compared to group 1 (p = 0.000 for all). In terms of wound strength parameters, substantial increases in bending stiffness and high-stress load were observed in groups 2, 3, and 4 compared to group 1 (p = 0.000 for all). Stereological examinations revealed decreases in neutrophil and macrophage counts and increases in fibroblast counts in groups 2, 3, and 4compared to group 1 (p = 0.000 for all). Blood vessel counts were more dominant in the PBM and PBM + CURgroups over group 1 (p = 0.000 for all). CFU and wound strength as well as macrophage, neutrophil, and fibroblast counts were found to be improved in the PBM + CUR and PBMgroups compared to the CUR group (ranging fromp = 0.000 top < 0.05). Better results were achieved in the PBM + CUR treatment over the PBM therapy. We determined therapy with PBM + CUR, PBM alone, and CUR alone substantially accelerated diabetic woundhealing in an IIDHWM of TIDM rats compared to control group. Concomitantly, the PBM + CUR and PBM groups attained significantly enhanced results for WCR, stereological parameters, and wound strength than the CUR group, with the PBM + CUR results being superior to those of the PBM group.

Retrospective Evaluation of the Use of a Dermal Substitute in Septorhinoplasty

At the present time, various methods exist for camouflaging the dorsum of the nose in septorhinoplasty. The subject of this paper is a retrospective descriptive evaluation of the surgical use of the bovine collagen/glycosaminoglycan matrix Integra Dermal Regeneration Template Single Layer Thin (IDRT-SL Thin) developed by Integra LifeSciences in septorhinoplasty procedures. The focus of this work is to evaluate the postoperative tolerability, the safety, and the course of wound healing when IDRT-SL Thin is applied as a collagen sheet in septorhinoplasty. The evaluation was performed using an evaluation form that was developed for this paper. Patients included in the study were followed up for one year postoperatively; however, the postoperative observation period considered in the evaluation was 14 weeks. The analysis of the surgical results shows relatively homogeneous results for the criteria and time period we examined. No notable complications were observed within the patient cohort up to the 14th postoperative week. Despite the limiting factors within the study due to the lack of a control group undergoing other surgical treatment procedures and the small number of patient cases, the observation period of six and 14 weeks applied in this study is suitable to determine the suitability and tolerability in principle. The results presented in this study can therefore be understood as a possible starting point for further investigations on the use of IDRT-SL Thin in septorhinoplasty.

Transcriptional changes in human palate and skin healing.

Most human tissue injuries lead to the formation of a fibrous scar and result in the loss of functional tissue. One adult tissue that exhibits a more regenerative response to injury with minimal scarring is the oral mucosa. We generated a microarray gene expression dataset to examine the response to injury in human palate and skin excisional biopsies spanning the first 7 days after wounding. Differential expression analyses were performed in each tissue to identify genes overexpressed or underexpressed over time when compared to baseline unwounded tissue gene expression levels. To attribute biological processes of interest to these gene expression changes, gene set enrichment analysis was used to identify core gene sets that are enriched over the time-course of the wound healing process with respect to unwounded tissue. This analysis identified gene sets uniquely enriched in either palate or skin wounds and gene sets that are enriched in both tissues in at least one time point after injury. Finally, a cell type enrichment analysis was performed to better understand the cell type distribution in these tissues and how it changes over the time course of wound healing. This work provides a source of human wound gene expression data that includes two tissue types with distinct regenerative and scarring phenotypes.

Platelet-rich fibrin vs. buccal advancement flap for closure of oroantral communications: a prospective clinical study

ObjectivesThe primary aim was to evaluate the success of the defect closure (tight or open) of oroantral communications (OAC) after treatment with platelet-rich fibrin (PRF) clots or a buccal advancement flap (BAF). Secondary outcome measurements were the evaluation of the wound healing, the displacement of the mucogingival border (MGB), and the pain level.Material and methodsFifty eligible patients with an OAC defect larger than 3 mm were randomly assigned to either PRF (test group, n = 25) or BAF (control group, n = 25) for defect closure. In a prospective follow-up program of 21 days, the defect closure healing process, the wound healing course using Landry’s wound healing index (score: 0–5), the displacement of the MGB, and the postoperative pain score were evaluated.ResultsFive patients in each group were lost to follow-up resulting in 40 patients (20 in each group) for continuous evaluation. On postoperative day 21 (study endpoint), no difference regarding success rate (defined as closure of OAC) was noticed between the test (90%; 18/20) and control group (90%; 18/20). A univariate analysis showed significant differences for age and defect size/height for the use of PRF between successful-tight and open–failed defect healing. At the final evaluation, a significantly (p = 0.005) better wound healing score, a lower displacement of the MGB as well as lower pain-score were seen for the use of PRF.ConclusionsBased on the findings of the current study, the use of platelet-rich fibrin represents a reliable and successful method for closure of oroantral communications. The use of PRF clots for defect filling is associated with lowered pain levels and less displacement of the mucogingival border.Clinical relevanceThe defect size should be taken into account when choosing the number and size of PRF plugs.

МОДЕЛЬ ДЛЯ ОЦЕНКИ РИСКА ЗАМЕДЛЕННОГО ТЕЧЕНИЯ РАНЕВОГО ПРОЦЕССА У БОЛЬНЫХ С ИЗБЫТОЧНОЙ МАССОЙ ТЕЛА

Objective: Develop a model for predicting the risk of a delayed and complicated course of wound healing in obese patients Methods: The study included 49 patients above 30 years of age (mean age 46.98±7.10 years) with a body mass index (BMI) above 25 kg/m2 (mean value 31.64±5.04 kg/m2 ), who underwent augmentation mammaplasty and aesthetic anterior abdominal wall reconstruction in the period from 2016 to 2018. In the postoperative period, the patients were divided into three groups depending on the wound healing pattern: Group I – complicated wound healing (n=21; 42.86%); Group II – delayed wound healing (n=16; 32.65%); Group III – standard wound healing (n=12; 24.49%). The assessment of the prognostic risk of developing a delayed and complicated wound healing was carried out using a new mathematical model, taking into account the insulin level (mIU/l) and spontaneous secretion of interleukin-1β (pg/ml). Logistic regression analysis was used to determine the significance of prognostic factors. The decision tree model was used to stratify risk groups. A receiver operating characteristic (ROC) analysis was used to assess the quality of the constructed model. Results: Using the decision tree, three risk classes of delayed and complicated wound healing were identified. The highest risk of developing postoperative wound complications (risk=95.0%, n=20) was observed in patients with insulin levels ≥14.0 mIU/l. The average level of risk was determined at the value of insulin &lt;14.0 mIU/l and spontaneous production of interleukin-1β ≥51.0 pg/ml (risk=50.0%, n=2). The lowest risk level of complications (risk=3.7%, n=27) was found with a combination of factors: insulin &lt;14.0 mIU/l and interleukin-1β spontaneous production &lt;51.0 pg/ml. The predictive quality of the constructed model is high (the area under the ROC curve is 0.98). Conclusion: The proposed prognostic model will allow the identification of patients with a high risk of delayed or complicated wound healing in the preoperative period and timely adjust the treatment tactics. Keywords: Overweight, wound healing, prognosis, non-healing wounds.

The role of polyamines in the regenerative process of skin aerobic-purulent wounds

Aliphatic polyamines (putrescine, spermidine, spermine) are organic polycations that play an important role in wound healing by stimulating several cellular mechanisms. In a human skin wound sample, the activity of the enzyme ornithine decarboxylase, which regulates the rate of polyamine synthesis, rapidly increases along the wound edges and leads to the activation of the polyamine synthesis cascade. Under the influence of polyamines, some signaling systems are also activated in wounds, which are the main pathways for the release of cellular mechanisms, and thanks to them, the healing process begins in wounds. For example, spermine induces the synthesis of urokinase-type plasminogen activator, the binding of which to the corresponding receptor at the wound margins executes the urokinase-type plasminogen activator and its receptor signaling system, which is the main driver of keratinocyte migration. Eukaryotic cell proliferation depends on precise modification of the eukaryotic initiation factor 5A1, in which spermidine plays an indispensable role. However, in addition to the significant functions performed by polyamines in the human body, polyamines are also necessary for the normal growth and development of fungi and bacteria. Small amounts of some microorganisms have a positive effect on the healing of wounds, but their increase, on the contrary, leads to the impairment of the normal course of wound healing due to their enhanced synthesis of polyamines. On the other hand, many studies show that excess ornithine decarboxylase and polyamines increase the risk of skin cancer. Suppression of polyamine synthesis by pathogenic microflora during wound healing can contribute to both rapid healing and the prevention of skin cancer. In our study, we offer a way of inhibition of polyamine synthesis by wound microflora for rapid wound healing and prevention of subsequent cancer. The medicinal mixture “Armenicum/Eflornithine” is a mixture of the drug “Armenicum” and α-difluoromethylornithine.

Green Synthesis and Evaluation of Lepidium didymum-mediated Silver Nanoparticles for in vitro Antibacterial Activity and Wound Healing in the Animal Model.

Wounds serve as an appropriate medium for the growth of pathogenic bacteria, and bacterial resistance to already available antibiotics demands new and safe approaches in the field of medicine. Silver nanoparticles (AgNPs) exhibited a wide range of applications in biomedicine and emerged as promising nano-antibiotics. The biological preparation of AgNPs by utilizing aqueous plant extract has become an encouraging alternative to traditional chemical methodologies, owing to a viable eco-friendly approach. In the present study, Lepidium didymum leaves extract was used for the biosynthesis of AgNPs-LD. The nanoparticles were characterized through UV-Vis spectroscopy, Fourier transforms infrared spectrometry (FTIR), Scanning electron microscopy (SEM), and X-ray diffraction (XRD). The antibacterial activity of AgNPs-LD was evaluated against Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, and Pseudomonas aeruginosa. Further, AgNPs-LD nanoparticles were incorporated into topical gels to evaluate their effectiveness for wound healing in the rat model. UV-visible spectra showed a surface resonance peak around 400 nm correlated with the synthesis of AgNPs; FTIR spectra verified the participation of phytochemicals present in L. didymum leaves extract in AgNPs-LD synthesis; and SEM revealed dispersed spherical nanoparticles as well as aggregated clusters. XRD analysis confirmed the crystalline nature, face-centered cubic lattice, and average crystallite size of 21.42 nm. The AgNPs-LD showed promising antibacterial activity against tested strains with a maximum zone of inhibition against P. aeruginosa and showed accelerated wound healing capacity comparable to control and standard treatments over the time course of wound healing. The current study concluded that biosynthesized AgNPs-LD nanoparticles are effective as antibacterial agents and are promising novel wound healing products for clinical applications.

A simplified method for monitoring cytokines in wound fluid.

Cytokines in wound fluid are used as surrogates for wound healing in clinical research. The current methods used to collect and process wound fluid are noninvasive but not optimal. The aim of this prospective study was to evaluate a method (NovaSwab) by which wound fluid is collected by a surface swab and eluted in a physiological buffer for subsequent cytokine analysis. Wound fluid from 12 patients with leg ulcers was assessed by NovaSwab at the start (Day 0) and at the end of a 23-h collection period of wound fluid retained by foam oblates beneath an occlusive film dressing (Day 1). GM-CSF, IL-1α, IL-1β, IL-6, IL-8, PDGF-AA, TNF-α and VEGF levels were measured by multiplex and electrochemiluminescence assays. IL-1α (2.4×), IL-1β (2.0×) and IL-8 (1.8×) levels increased from Day 0 to Day 1 as detected by NovaSwab, indicating local production of these polypeptides in the wounds. On Day 1, the NovaSwab method yielded higher levels of IL-1α (4.0×), IL-1β (2.7×) and IL-6 (2.7×), and 35% lower levels of VEGF than those in wound fluid accumulated for 23 h in foam oblates (on average, 5ml of wound fluid). In vitro experiments showed that the investigated cytokines in cell-free wound fluid were recovered in a quantitative manner by the NovaSwab method. We conclude that the method presented here is a promising research tool to study the kinetics of soluble cytokines over the course of wound healing. More studies are needed to determine the interobserver variation and reproducibility of the NovaSwab method.

Features of microcirculatory responses in experimental wound area in white rats

Objective: to examine changes in the microcirculatory bed parameters via laser Doppler flowmetry in the course of wound healing and the possibility of their use for upgrading the technology of evaluating the effectiveness of wound healing agents. Materials and Methods. The studies were performed on 25 white rats distributed between two groups: 10 control animals (intact rats) and 15 animals with a full-thickness experimental skin defect. The microcirculation parameters in the skin of experimental wound edges in rats were evaluated using laser Doppler flowmetry, and histological preparations of tissues in the wound area were analyzed. Results. Changes in skin microcirculation at the wound edges were characterized by inflammatory hyperemia manifested by an increase in the perfusion index by 27% and augmented normalized amplitudes of myogenic, respiratory and cardiogenic oscillations. Changes in microcirculation were verified by the morphological picture of inflammation, which reflects an increase in the number of vessels fully filled with arterial and venous blood, as well as in leukocyte infiltration of the wound edges and bottom. Conclusion. Monitoring of microcirculatory disorders occurring in the area of skin wounds allows assessing the dynamics of the reparative process, which could be used for developing and evaluating the effectiveness of existing medicamentous and non-medicamentous methods of stimulating regeneration.

WOUND HEALING ACTIVITY OF A GELATIN-BASED HYDROGEL CONTAINING 2% ETHANOLIC EXTRACT OF HIMATANTHUS BRACTEATUS

Objectives To analyze the effect of topical application of a photopolymerizable hydrogel based on methacrylated gelatin containing 2% ethanolic extract of Himatanthus bracteatus (GelMA-HB) on wound healing in rodents. Study Design Standard-sized (0.8 cm diameter) round-shaped wounds were made in the back of Wistar rats treated with photopolymerizable hydrogel based on methacrylated gelatin (GelMA), GelMA-HB, and saline (CTR). The animals were euthanized after 3, 7, and 14 days. Wound retraction index (WRi), wound healing histologic grading (WHHG), and immunohistochemical expression of α-SMA and CD105 were assessed for myofibroblastic differentiation (MFd) and microvascular density (MVd) analysis, respectively. Results The WRi and WHHG in GelMA-HB were significantly greater than in GelMA (P < .05) and CTR (P < .01) over the full time course of the experiment. Both the MFd and MVd were greater in GelMA-HB than in CTR on day 3 (P < .05) and day 7 (P < .001). Conclusions The GelMA-based formulation containing ethanolic extract of H. bracteatus improved wound healing in a rodent model, and such biological effects might be related to the modulation of myofibroblastic and microvascular differentiation over the course of wound healing. To analyze the effect of topical application of a photopolymerizable hydrogel based on methacrylated gelatin containing 2% ethanolic extract of Himatanthus bracteatus (GelMA-HB) on wound healing in rodents. Standard-sized (0.8 cm diameter) round-shaped wounds were made in the back of Wistar rats treated with photopolymerizable hydrogel based on methacrylated gelatin (GelMA), GelMA-HB, and saline (CTR). The animals were euthanized after 3, 7, and 14 days. Wound retraction index (WRi), wound healing histologic grading (WHHG), and immunohistochemical expression of α-SMA and CD105 were assessed for myofibroblastic differentiation (MFd) and microvascular density (MVd) analysis, respectively. The WRi and WHHG in GelMA-HB were significantly greater than in GelMA (P < .05) and CTR (P < .01) over the full time course of the experiment. Both the MFd and MVd were greater in GelMA-HB than in CTR on day 3 (P < .05) and day 7 (P < .001). The GelMA-based formulation containing ethanolic extract of H. bracteatus improved wound healing in a rodent model, and such biological effects might be related to the modulation of myofibroblastic and microvascular differentiation over the course of wound healing.

Dually-Thermoresponsive Hydrogel with Shape Adaptability and Synergetic Bacterial Elimination in the Full Course of Wound Healing.

Incomplete contact between a pre-formed hydrogel and irregular wound limits the therapeutic effect of the dressing and increases the risk of infection; while great concerns have remained regarding the potential toxicity of the residual additives of chemical crosslinking for in situ forming hydrogels. Therefore, it is desirable to develop a self-adaptive hydrogel in response to skin temperature with shape adaptability and efficient antibacterial properties to prevent microbial invasion. Herein, a dually-thermoresponsive hydrogel composed of poly(N-isopropylacrylamide) (PNIPAm) and methacrylated κ-carrageenan (MA-κ-CA) is designed with compliance at physiological temperature to realize shape adaptability for completely covering irregular wounds. Furthermore, the hydrogel with near-infrared (NIR)-responsive polypyrrole-polydopamine nanoparticles (PPy-PDA NPs) and Zn2+ -derived zeolitic imidazolate framework (ZIF-8) can generate localized heat and gradually release Zn2+ to realize safe, effective synergetic photothermal-chemical bactericidal capability. In addition, the release rate of Zn2+ can be accelerated by NIR-induced heating, and thus a more efficient sterilization can be provided to severely infected wounds. Therefore, the proposed hydrogel would serve as a promising wound dressing for the full course of wound healing, with the abilities of perfectly covering the wound and adapting to regenerating tissue, and controllable photothermal-chemical antibacterial capability to reach high bactericidal efficiency and long-term release of antibacterial agents.

Simvastatin cream alleviates dermal fibrosis in a rabbit ear hypertrophic scar model.

Hypertrophic scars (HTS) result from injury to the skin and represent a clinical burden with limited treatment options. Previously, we demonstrated that statin drugs could attenuate HTS formation, but convenient topical delivery and retention of these drugs at the wound site remains a challenge. Here, we aimed to develop a topical cream formulation that can deliver statin drugs simply and conveniently to reduce scar hypertrophy. We formulated creams containing 10% pravastatin, 2% simvastatin, and 10% simvastatin. We tested these creams for their ability to reduce scar hypertrophy and attenuate dermal fibrosis in a clinically relevant HTS wound model performed in rabbit ear skin. We also monitored trans-epidermal water loss (TEWL) over the course of wound healing in order to understand the effects of statin treatment on epidermal barrier recovery. Of the three creams formulated, only application of 10% simvastatin cream significantly attenuated hypertrophy of resultant scars compared with vehicle cream application. Application of 10% simvastatin cream resulted in a decrease in macrophage and myofibroblast density at post-operative day 28 (POD28) harvest. Application of 10% simvastatin cream resulted in visible symptoms of dryness and increased TEWL at POD28, but subsequent withdrawal of statin cream treatment resulted in rapid alleviation of dryness and decrease in TEWL back to normal levels. Our data demonstrate that topical administration of 10% simvastatin cream antagonizes dermal fibrosis and reduces hypertrophy in an HTS model, and withdrawal of the cream enables recovery of epidermal barrier and resolution of skin dryness.

Objective and Quantitative Evaluation of Spontaneous Pain-Like Behaviors Using Dynamic Weight-Bearing System in Mouse Models of Postsurgical Pain.

BackgroundThe paucity of objective and reliable measurements of pain-like behaviors has impeded the translatability of mouse models of postsurgical pain. The advanced dynamic weight-bearing (DWB) system enables evaluation of spontaneous pain-like behaviors in pain models. This study investigated the suitability and efficiency of the DWB system for assessing spontaneous pain-like behaviors and analgesic therapies in murine models of postsurgical pain.MethodsMale adult C57BL/6JJcl mice were subjected to multiple surgical pain models with distinct levels of invasiveness, including a superficial incisional pain model involving only hind paw skin incision, deep incisional pain model that also involved incision and elevation of the underlying hind paw muscles, and orthopedic pain model involving tibial bone fracture and fixation with a pin (fracture and pinning [F/P] model). Spontaneous pain-like behaviors post-surgery were evaluated using weight distribution, pawprint area of the operated paw in the DWB system, and guarding pain score. Mechanical hypersensitivity was assessed using the von Frey test. The therapeutic effects of analgesics (diclofenac and buprenorphine for the deep incision model and diclofenac for the F/P model) were evaluated using the DWB system and von Frey test.ResultsThe von Frey test demonstrated contradictory results between superficial and deep incisional pain models. The DWB system captured weight distribution changes in the operated hind paw, in accordance with the invasiveness and time course of wound healing in these surgical pain models. The reduction in weight-bearing on the operated paw correlated with guarding score, degree of paw swelling, and local expression of inflammatory mediators. DWB enabled accurate evaluation of the pharmacological effects of analgesics for detecting attenuation of surgery-induced weight-bearing changes in these models.ConclusionThe DWB system serves as an objective and reliable method for quantifying pain-like behaviors and evaluating the therapeutic effects of analgesics in mouse models of postsurgical pain models.