A Control System Design to Establish Dose-Response Relationships in Wound Healing Therapy

Advanced biophysical wound healing therapies can apply mechanical, electrical, or light energy to re-stimulate healing processes in chronic wounds. Despite the growing evidence of the clinical efficacy of these therapies, the optimal treatment stimulation parameters remain unknown and there are no standard treatment protocols. We introduce a closed-loop control design as an experimental system to study the dose-response of wound healing therapy treatment within a prescribed multidimensional and multimodal stimulation parameter space. Systems engineering approaches are applied to the control problem for estimation of a transfer function and model equations derived for use in optimal model-based control. The experimental control system design consisted of simultaneous application of biophysical energies inputted into a wound system. A study design set up including the use of negative pressure wound therapy, electrical stimulation therapy, and photobiomodulation device systems was described. Treatment stimulation parameters were selected from experimental ranges used in the scientific literature. Classical control methods and model-based control were suggested for model selection and evaluation and design of the overall control system. An experimental design for multimodal biophysical wound healing therapy control system is introduced to establish the dose-response interactions for development of therapeutic applications and device design.

Establishment of a three-dimensional finite element model for gunshot wounds to the human mandible

Objective:To investigate the feasibility of a finite element model as an ideal research tool for human maxillofacial gunshot wounds.Methods:Mandible CT scan data on the Chinese Visible Human were imported into MIMICS software to obtain the surface mesh of the mandible.Then,these surface-meshed models were imported into ANSA software for automatic net generation.Elements and nodes were partitioned on the basis of the mesh to obtain a three-dimensional finite element model for the mandible with every internal parameter consistent with those of our previously developed model in the pig mandible.The finite element model was imported into LS-DYNA for computation.Finally,the LS-POST was used to complete the simulation and the measurements.Results:A three-dimensional finite element model was successfully established for gunshot wounds in the human mandible.The stress distribution and the degree of injury were simulated dynamically for shots from two types of projectiles in the mandible at one entry angle and at three impact velocities.Conclusion:Three-dimensional finite element models will become ideal research tools for treatment of ballistic wounds of the human maxillofacial region.Using this human mandibular model as a foundation,we will be able to successfully develop three-dimensional finite element models for human maxillofacial gunshot wounds.

Open wound management of esophagocutaneous fistula in unstable cervical spine after corpectomy and multilevel laminectomy:A case report and review of the literature

A 67-year-old female patient developed an esophagocutaneous fistula 4 mo after C4 and C5 partial corpectomy. Plain radiograph and computed tomography(CT) scan of cervical spine showed inferior screws pullout with plate migration that caused the esophageal perforation. Management included removal of anterior hardware, revision C4-5 corpectomy, iliac crest strut autograft and halo orthosis immobilization. The fistula was treated using antibiotics and a 10-french gauge rubber tube for daily irrigation and Penrose drain. At 3 mo, the esophagocutaneous fistula healed and the patient resumed oral feeding. Six months follow-up CT scan showed sound fusion with graft incorporation. At two-year follow-up, patient denied any neck pain or dysphagia. This case report presents a successful outcome of a conservative open wound management without attempted repair. The importance of this case report is to highlight this treatment method that may be considered in such a rare complication particularly if surgical repair failed.

The Application of Bilayer Artificial Dermis Combined with VSD Technology in Chronic Wounds

Background: Bilayer artificial dermis promotes wound healing and offers a treatment option for chronic wounds. Aim: Examine the clinical efficacy of bilayer artificial dermis combined with Vacuum Sealing Drainage (VSD) technology in the treatment of chronic wounds. Method: From June 2021 to December 2023, our hospital treated 24 patients with chronic skin tissue wounds on their limbs using a novel tissue engineering product, the bilayer artificial dermis, in combination with VSD technology to repair the wounds. The bilayer artificial dermis protects subcutaneous tissue, blood vessels, nerves, muscles, and tendons, and also promotes the growth of granulation tissue and blood vessels to aid in wound healing when used in conjunction with VSD technology for wound dressing changes in chronic wounds. Results: In this study, 24 cases of chronic wounds with exposed bone or tendon larger than 1.0 cm2 were treated with a bilayer artificial skin combined with VSD dressing after wound debridement. The wounds were not suitable for immediate skin grafting. At 2 - 3 weeks post-treatment, good granulation tissue growth was observed. Subsequent procedures included thick skin grafting or wound dressing changes until complete wound healing. Patients were followed up on average for 3 months (range: 1 - 12 months) post-surgery. Comparative analysis of the appearance, function, skin color, elasticity, and sensation of the healed chronic wounds revealed superior outcomes compared to traditional skin fl repairs, resulting in significantly higher satisfaction levels among patients and their families. Conclusion: The application of bilayer artificial dermis combined with VSD technology for the repair of chronic wounds proves to be a viable method, yielding satisfactory therapeutic effects compared to traditional skin flap procedures.

Platelet-rich plasma treatment for chronic wounds:A case report and literature review

BACKGROUND Wound healing is a complicated process that can be heavily influenced by patient comorbidities,in some cases leading to a chronic non-healing wound.Evidence presented in the medical literature supporting the clinical use of autologous platelet-rich plasma(PRP)in treatment of such wounds is becoming increasingly compelling.Mechanisms involved include complex interactions between the patient’s thrombocytes,cytokines,and growth factors.CASE SUMMARY We present a case of a 72-year-old male patient with a long-standing chronic wound and multiple comorbidities.Over the course of more than 7 months,the patient was unsuccessfully treated with all routinely used measures,including different dressing approaches.Multiple antibiotic regimens were administered for wound infection,with repeated evaluation of microbiological swab results.Finally,after three PRP applications,the wound showed clinical improvement with complete restitution of the epithelial layer of the skin.CONCLUSION PRP treatment may be beneficial to reduce healing time in chronic wounds.

A mechanically stable self-pumping organohydrogel dressing with aligned microchannels for accelerated diabetic wound healing

Self-pumping dressings(SPDs)have been developed as a new type of effective material for the drainage of excessive wound exudates based on the structure of asymmetric wettability.However,current SPDs are easy to lose their asymmetric wettability due to the weak interfacial mechanical stability between the hydrophobic and hydrophilic layers.Herein,we report an integrated self-pumping organohydrogel dressing with aligned microchannels(SPD-AM),prepared by an ice-templating-assisted wetting-enabled-transfer(WET)polymerization strategy,that can accelerate the healing process of diabetic wounds.The WET polymerization strategy enables strong interfacial mechanical stability between the hydrophobic organogel and hydrophilic hydrogel layers.The aligned microchannels greatly improve the draining capability of SPDs.Taking a diabetic rat model as an example,the SPD-AM can significantly reduce the bacterial colonization with low inflammatory responses,enhance dermal remodeling by about 47.31%,and shorten wound closure time by about 1/5 compared with other dressings,ultimately accelerating diabetic wound healing.This study is valuable for developing next-generation SPDs with stable mechanical performance for clinical applications.

Understanding wound healing in obesity

Obesity has become more prevalent in the global population.It is associated with the development of several diseases including diabetes mellitus,coronary heart disease,and metabolic syndrome.There are a multitude of factors impacted by obesity that may contribute to poor wound healing outcomes.With millions worldwide classified as obese,it is imperative to understand wound healing in these patients.Despite advances in the understanding of wound healing in both healthy and diabetic populations,much is unknown about wound healing in obese patients.This review examines the impact of obesity on wound healing and several animal models that may be used to broaden our understanding in this area.As a growing portion of the population identifies as obese,understanding the underlying mechanisms and how to overcome poor wound healing is of the utmost importance.

Ultrastable in-situ silver nanoparticle dressing for effective prevention and treatment of wound infection in emergency

The use of antibacterial dressings is crucial in the prevention and treatment of wound infection in emergency sit-uations.However,the efficacy of dressings is compromised by long-term storage or exposure to harsh conditions.Here,an ultrastable in-situ silver nanoparticle dressing(AgSNP@CD)was prepared for effective prevention and treatment of wound infection in emergency.The fabrication process of AgSNP@CD is simple,suitable for large-scale production.Due to the strong interaction between the in-situ synthesized AgNPs and the cotton fabric,AgSNP@CD owned remarkable stability,thus retaining its antimicrobial efficacy even after long-term storage(up to 2 years)and under extreme conditions(damp heat,low temperatures,low-oxygen,water immersion,acid-alkali erosion).Both in vitro and in vivo results demonstrated the extraordinary antibacterial efficacy and stability of AgSNP@CD,facilitating infection prevention and wound healing in extreme conditions.In particular,AgSNP@CD exhibited a superior treatment effect on severe bacteria-infected trauma and can prevent the occur-rence of sepsis effectively.The exceptional stability and antibacterial efficacy of AgSNP@CD under complex and extreme conditions make it a well-suited dressing strategy for the prevention and treatment of wound infection in emergency.

Research advances in smart responsive-hydrogel dressings with potential clinical diabetic wound healing properties

The treatment of chronic and non-healing wounds in diabetic patients remains a major medical problem.Recent reports have shown that hydrogel wound dressings might be an effective strategy for treating diabetic wounds due to their excellent hydrophilicity,good drug-loading ability and sustained drug release properties.As a typical example,hyaluronic acid dressing(Healoderm)has been demonstrated in clinical trials to improve wound-healing efficiency and healing rates for diabetic foot ulcers.However,the drug release and degradation behavior of clinically-used hydrogel wound dressings cannot be adjusted according to the wound microenvironment.Due to the intricacy of diabetic wounds,antibiotics and other medications are frequently combined with hydrogel dressings in clinical practice,although these medications are easily hindered by the hostile environment.In this case,scientists have created responsive-hydrogel dressings based on the microenvironment features of diabetic wounds(such as high glucose and low pH)or combined with external stimuli(such as light or magnetic field)to achieve controllable drug release,gel degradation,and microenvironment improvements in order to overcome these clinical issues.These responsive-hydrogel dressings are anticipated to play a significant role in diabetic therapeutic wound dressings.Here,we review recent advances on responsive-hydrogel dressings towards diabetic wound healing,with focus on hydrogel structure design,the principle of responsiveness,and the behavior of degradation.Last but not least,the advantages and limitations of these responsive-hydrogels in clinical applications will also be discussed.We hope that this review will contribute to furthering progress on hydrogels as an improved dressing for diabetic wound healing and practical clinical application.

Double-nylon purse-string suture in closing postoperative wounds following endoscopic resection of large(≥3 cm)gastric submucosal tumors

BACKGROUND Endoscopic full-thickness resection(EFTR)of gastric submucosal tumors(SMTs)is safe and effective;however,postoperative wound management is equally important.Literature on suturing following EFTR for large(≥3 cm)SMTs is scarce and limited.AIM To evaluate the efficacy and clinical value of double-nylon purse-string suture in closing postoperative wounds following EFTR of large(≥3 cm)SMTs.METHODS We retrospectively analyzed the data of 85 patients with gastric SMTs in the fundus of the stomach or in the lesser curvature of the gastric body whose wounds were treated with double-nylon purse-string sutures after successful tumor resection at the Endoscopy Center of Renmin Hospital of Wuhan University.The operative,postoperative,and follow-up conditions of the patients were evaluated.RESULTS All tumors were completely resected using EFTR.36(42.35%)patients had tumors located in the fundus of the stomach,and 49(57.65%)had tumors located in the body of the stomach.All patients underwent suturing with double-nylon sutures after EFTR without laparoscopic assistance or further surgical treatment.Postoperative fever and stomach pain were reported in 13(15.29%)and 14(16.47%)patients,respectively.No serious adverse events occurred during the intraoperative or postoperative periods.A postoperative review of all patients revealed no residual or recurrent lesions.CONCLUSION Double-nylon purse-string sutures can be used to successfully close wounds that cannot be completely closed with a single nylon suture,especially for large(≥3 cm)EFTR wounds in SMTs.

Mesenchymal stem cell-derived extracellular vesicles in skin wound healing:roles,opportunities and challenges

Skin wounds are characterized by injury to the skin due to trauma,tearing,cuts,or contusions.As such injuries are common to all human groups,they may at times represent a serious socioeconomic burden.Currently,increasing numbers of studies have focused on the role of mesenchymal stem cell(MSC)-derived extracellular vesicles(EVs)in skin wound repair.As a cell-free therapy,MSC-derived EVs have shown significant application potential in the field of wound repair as a more stable and safer option than conventional cell therapy.Treatment based on MSC-derived EVs can significantly promote the repair of damaged substructures,including the regeneration of vessels,nerves,and hair follicles.In addition,MSC-derived EVs can inhibit scar formation by affecting angiogenesis-related and antifibrotic pathways in promoting macrophage polarization,wound angiogenesis,cell proliferation,and cell migration,and by inhibiting excessive extracellular matrix production.Additionally,these structures can serve as a scaffold for components used in wound repair,and they can be developed into bioengineered EVs to support trauma repair.Through the formulation of standardized culture,isolation,purification,and drug delivery strategies,exploration of the detailed mechanism of EVs will allow them to be used as clinical treatments for wound repair.In conclusion,MSCderived EV-based therapies have important application prospects in wound repair.Here we provide a comprehensive overview of their current status,application potential,and associated drawbacks.

ROS Balance Autoregulating Core-Shell CeO_(2)@ZIF-8/Au Nanoplatform for Wound Repair

Reactive oxygen species(ROS)plays important roles in living organisms.While ROS is a double-edged sword,which can eliminate drug-resistant bacteria,but excessive levels can cause oxidative damage to cells.A core–shell nanozyme,Ce O_(2)@ZIF-8/Au,has been crafted,spontaneously activating both ROS generating and scavenging functions,achieving the multifaceted functions of eliminating bacteria,reducing inflammation,and promoting wound healing.The Au Nanoparticles(NPs)on the shell exhibit high-efficiency peroxidase-like activity,producing ROS to kill bacteria.Meanwhile,the encapsulation of Ce O_(2) core within ZIF-8 provides a seal for temporarily limiting the superoxide dismutase and catalase-like activities of Ce O_(2) nanoparticles.Subsequently,as the ZIF-8 structure decomposes in the acidic microenvironment,the Ce O_(2) core is gradually released,exerting its ROS scavenging activity to eliminate excess ROS produced by the Au NPs.These two functions automatically and continuously regulate the balance of ROS levels,ultimately achieving the function of killing bacteria,reducing inflammation,and promoting wound healing.Such innovative ROS spontaneous regulators hold immense potential for revolutionizing the field of antibacterial agents and therapies.

ON101 Cream Increases the Wound Healing Rate in Diabetic Patients with Uremia—Cases Report

Diabetic patients who underwent long-term dialysis may increase the prevalence of foot ulceration. In addition, diabetic foot ulcer (DFUs) patients with end-stage renal disease (ESRD) do not heal well, and the amputation rate is 6.5 - 10 times higher compared to the non-nephropathic diabetic population. Thus, a suitable therapeutic agent was needed. ON101 is a topical cream that promotes diabetic wound healing through a unique macrophage-regulating ability. In this case series, we included 5 diabetes patients (mean age 54.6 ± 8.7 years, 4 mal) with ESRD (mean eGFR 7.4 ± 3.35 mL/min/1.73m2) and had experienced dialysis for at least 4.5 years. These patients also have UT (University of Texas) grade 2A DFUs that have existed for at least 1.5 months (mean ulcer duration 8.3 ± 8.97 months). These subjects were applied ON101 twice daily for up to 20 weeks, and wound size was recorded during treatment. Among these subjects, three ulcers (patient No. 1, 2, and 3) completely healed within 10 weeks upon ON101 application, and one ulcer was 99% reduced at 20th weeks (patient No. 4). Only one ulcer didn’t show an obvious response that may due to poor compliance in wound care and glucose control. In summary, the overall healing rate was 60%, suggesting ON101 performed equivalence healing efficacy in dialysis patients compared with those who did not have dialysis.

STAB模式在神经外科专科护士培训中的应用

目的探讨STAB模式在神经外科专科护士培训中的应用效果。方法选取2014~2020年在我院神经外科专科护士示范基地参与培训的252名护士作为研究对象,根据培训时间将研究对象分为对照组(n=98)和观察组(n=154),其中对照组采用传统专科护士培养模式,观察组采用STAB模式,进行为期3个月的培训。培训结束后,比较两组护士在理论、操作、论文答辩、护理查房等方面考核成绩,并通过问卷调查的形式进行教学满意度评价。结果观察组护士在理论、论文答辩、护理查房方面的考核成绩明显优于对照组(P<0.05);观察组护士在授课模式、教学效果、教学总体评价的满意度明显优于对照组(P<0.05)。结论与传统培训模式相比,采用STAB模式进行神经外科专科护士培训,可在一定程度上提高专科护士在理论、技能、科研等方面的综合能力。

Transplantation of a pectoralis major flap for the repair of myiasis wounds

Myiasis is a disease caused by the invasion and colonization of human tissues and organs by the larvae of flies.This is manifested by the formation of necrotic tissue in the lesion,the colonization of fly eggs and the spread of fly larvae.This disease is mostly found in areas with poor sanitary conditions.Poor wound care,necrotic tissue formation,reduced immunity,and frequent contact with flies are risk factors for this disease.Myiasis can be divided into obligate and facultative parasitism,^([1])while some scholars have classified myiasis according to its location.^([2])In addition,some cases of myiasis are secondary to wound infection or poor surgical maintenance.^([3,4]).

High-strength antiswelling adhesive achieves both hemostasis and wound healing

Skin is one of the most vulnerable tissues,but there is a lack of injectable bioactive hydrogel dressings,which possess high strength,antiswelling capacity,and wet tissue adhesiveness,but also a rapid gelling process to enable rapid hemostasis,sutureless wound closure,and scarless healing of infected skin wounds[1e5].A new injectable,antibacterial,and multifunctional hydrogel dressings based on poly(citric acid-co-polyethylene glycol)-g-dopamine(PCPD)and amino-terminated Pluronic F127(APF)mi-celles loaded with astragaloside IV(AS)was developed for this pur-pose,as shown in Fig.1A[6].

A Skin-Inspired Self-Adaptive System for Temperature Control During Dynamic Wound Healing

The thermoregulating function of skin that is capable of maintaining body temperature within a thermostatic state is critical.However,patients suffering from skin damage are struggling with the surrounding scene and situational awareness.Here,we report an interactive self-regulation electronic system by mimicking the human thermos-reception system.The skin-inspired self-adaptive system is composed of two highly sensitive thermistors(thermal-response composite materials),and a low-power temperature control unit(Laserinduced graphene array).The biomimetic skin can realize self-adjusting in the range of 35–42℃,which is around physiological temperature.This thermoregulation system also contributed to skin barrier formation and wound healing.Across wound models,the treatment group healed~10%more rapidly compared with the control group,and showed reduced inflammation,thus enhancing skin tissue regeneration.The skin-inspired self-adaptive system holds substantial promise for nextgeneration robotic and medical devices.

Telencephalic stab wound injury induces regenerative angiogenesis and neurogenesis in zebrafish:unveiling the role of vascular endothelial growth factor signaling and microglia

After brain damage,regenerative angiogenesis and neurogenesis have been shown to occur simultaneously in mammals,suggesting a close link between these processes.However,the mechanisms by which these processes interact are not well understood.In this work,we aimed to study the correlation between angiogenesis and neurogenesis after a telencephalic stab wound injury.To this end,we used zebrafish as a relevant model of neuroplasticity and brain repair mechanisms.First,using the Tg(fli1:EGFP×mpeg1.1:mCherry)zebrafish line,which enables visualization of blood vessels and microglia respectively,we analyzed regenerative angiogenesis from 1 to 21 days post-lesion.In parallel,we monitored brain cell proliferation in neurogenic niches localized in the ventricular zone by using immunohistochemistry.We found that after brain damage,the blood vessel area and width as well as expression of the fli1 transgene and vascular endothelial growth factor(vegfaa and vegfbb)were increased.At the same time,neural stem cell proliferation was also increased,peaking between 3 and 5 days post-lesion in a manner similar to angiogenesis,along with the recruitment of microglia.Then,through pharmacological manipulation by injecting an anti-angiogenic drug(Tivozanib)or Vegf at the lesion site,we demonstrated that blocking or activating Vegf signaling modulated both angiogenic and neurogenic processes,as well as microglial recruitment.Finally,we showed that inhibition of microglia by clodronate-containing liposome injection or dexamethasone treatment impairs regenerative neurogenesis,as previously described,as well as injury-induced angiogenesis.In conclusion,we have described regenerative angiogenesis in zebrafish for the first time and have highlighted the role of inflammation in this process.In addition,we have shown that both angiogenesis and neurogenesis are involved in brain repair and that microglia and inflammation-dependent mechanisms activated by Vegf signaling are important contributors to these processes.This study paves the way for a better understanding of the effect of Vegf on microglia and for studies aimed at promoting angiogenesis to improve brain plasticity after brain injury.

Eyelid Wounds: Epidemiological, Clinical and Etiological Aspects

Purpose: The aim is to show epidemiological, clinical and etiological characteristics of palpebral wounds. Methodology: This was a retrospective study focusing on patients with an eyelid wound, over a 10-year period from 2012 to 2021. We collected and analyzed the data using Excel. Results: The frequency of eyelid wounds was 0.1%. The average age of our patients was 19.38 years with a range of 1 and 62 years. The sex ratio was 3.7. Eighty-one percent of patients lived in Dakar. Fifty-seven percent (57%) of patients consulted less than 24 hours after the trauma and 7% of patients on D1. The circumstances were brawls (11%), domestic accidents (9%), road accidents (6%), and work accidents (6%). We noted 1 case of dog bite. Thirteen patients presented with post-traumatic decreased visual acuity. Involvement of the isolated upper eyelid was noted in 40% of cases and both eyelids in 15% of cases. Involvement of the lacrimal ducts was noted in 17% of cases, and that of the free edge in 21% of cases. Eyelid wounds were associated with eyeball damage in 21% of cases. Various associated lesions were observed. Ninety-one percent of patients received surgical treatment. Three cases of superinfections, 1 case of conjunctival granuloma and 1 case of phthysis of the eyeball with postoperative retinal detachment were noted. Conclusion: Eyelid sores are relatively common in our context. They require rapid surgical treatment in order to preserve the functional and aesthetic prognosis. .

Antimicrobial,antibiofilm,angiogenesis,anti-inflammatory,and wound healing activities of zinc nanoparticles green synthesized using Ferula macrecolea extract

Objective:To assess the antimicrobial,antibiofilm,anti-inflammatory,angiogenic,and wound healing activities of zinc nanoparticles(ZNPs)green synthesized using Ferula macrecolea extract.Methods:The green synthesis was conducted using the precipitation method.Then,the minimum inhibitory concentration(MIC),minimum bactericidal concentration(MBC),and minimum biofilm inhibition concentration 50%(MBIC50)of ZNPs against Staphylococcus aureus(S.aureus)and Pseudomonas aeruginosa(P.aeruginosa)were evaluated.The effects of ZNPs on the gene expressions of Staphylococcus spp.[intracellular adhesion A(icaA)and D(icaD)]and P.aeruginosa(rhlI and rhlR)were investigated using quantitative real-time PCR.In addition,the effects of ZNPs on wound healing,angiogenesis,and anti-inflammatory markers were assessed.Results:The green-synthesized ZNPs demonstrated significant antimicrobial efficacy against S.aureus and P.aeruginosa.The biofilm formation in S.aureus and P.aeruginosa was also inhibited by ZNPs with MBIC50 values of 3.30μg/mL and 2.08μg/mL,respectively.Additionally,ZNPs downregulated the expression of biofilm-related genes icaA,icaD,rhlI,and rhlR in the tested bacteria.They also demonstrated promising in vitro wound healing effects by promoting fibroblast cell proliferation and wound closure in a dose-dependent manner.A significant increase in the expression of HLA-G5 and VEGF-A genes as well as a marked decrease in the expression of NF-κB,IL-1β,and TNF-αgenes were observed in cells treated with ZNPs compared to the control group(P<0.05).Conclusions:ZNPs display promising antibacterial effects against S.aureus and P.aeruginosa and wound-healing effects by inhibiting biofilm formation,inducing angiogenesis,and reducing inflammation.However,further studies must be conducted to specify the accurate mechanisms of action and toxicity of ZNPs.