Impact of tibial transverse transport in tissue regeneration and wound healing with perspective on diabetic foot ulcers

In this editorial,we comment on an article by Liao et al published in the current issue of the World Journal of Diabetes.We focus on the clinical significance of tibial transverse transport(TTT)as an effective treatment for patients with diabetic foot ulcers(DFU).TTT has been associated with tissue regeneration,improved blood circulation,reduced amputation rates,and increased expression of early angiogenic factors.Mechanistically,TTT can influence macrophage polarization and growth factor upregulation.Despite this potential,the limitations and conflicting results of existing studies justify the need for further research into its optimal application and development.These clinical implications highlight the efficacy of TTT in recalcitrant DFU and provide lasting stimuli for tissue re-generation,and blood vessel and bone marrow improvement.Immunomodu-lation via systemic responses contributes to its therapeutic potential.Future studies should investigate the underlying molecular mechanisms to enhance our understanding and the efficacy of TTT.This manuscript emphasizes the potential of TTT in limb preservation and diabetic wound healing and suggests avenues for preventive measures against limb amputation in diabetes and peripheral artery disease.Here,we highlight the clinical significance of the TTT and its importance in healing DFU to promote the use of this technique in tissue regeneration.

Neuroprotection of hyperbaric oxygen therapy in sub-acute traumatic brain injury:not by immediately improving cerebral oxygen saturation and oxygen partial pressure

Although hyperbaric oxygen （HBO） therapy can promote the recovery of neural function in patients who have suffered traumatic brain injury （TBI）, the underlying mechanism is unclear. We hypothesized that hyperbaric oxygen treatment plays a neuroprotective role in TBI by increasing regional transcranial oxygen saturation （rSO2） and oxygen partial pressure （PaO2）. To test this idea, we compared two groups： a control group with 20 healthy people and a treatment group with 40 TBI patients. The 40 patients were given 100% oxygen of HBO for 90 minutes. Changes in rSO2 were measured. The controls were also examined for rSO2 and PaO2, but received no treatment, rSO2 levels in the patients did not differ significantly after treatment, but levels before and after treatment were significantly lower than those in the control group. PaO2 levels were significantly decreased after the 30-minute HBO treatment. Our findings suggest that there is a disorder of oxygen metabolism in patients with sub-acute TBI. HBO does not immediately affect cerebral oxygen metabolism, and the underlying mechanism still needs to be studied in depth.

A decellularized nerve matrix scaffold inhibits neuroma formation in the stumps of transected peripheral nerve after peripheral nerve injury

Traumatic painful neuroma is an intractable clinical disease characterized by improper extracellular matrix(ECM)deposition around the injury site.Studies have shown that the microstructure of natural nerves provides a suitable microenvironment for the nerve end to avoid abnormal hyperplasia and neuroma formation.In this study,we used a decellularized nerve matrix scaffold(DNM-S)to prevent against the formation of painful neuroma after sciatic nerve transection in rats.Our results showed that the DNM-S effectively reduced abnormal deposition of ECM,guided the regeneration and orderly arrangement of axon,and decreased the density of regenerated axons.The epineurium-perilemma barrier prevented the invasion of vascular muscular scar tissue,greatly reduced the invasion ofα-smooth muscle actin-positive myofibroblasts into nerve stumps,effectively inhibited scar formation,which guided nerve stumps to gradually transform into a benign tissue and reduced pain and autotomy behaviors in animals.These findings suggest that DNM-S-optimized neuroma microenvironment by ECM remodeling may be a promising strategy to prevent painful traumatic neuromas.

An Overview of the Use of Medicinal Plants in Regenerative Dentistry

Aim: The oral cavity has the particularity to host multiple hard and soft tissues, in this paper, we will discuss the current therapies that lead to cell differentiation by regenerative therapies and the future alternatives proposed by medicinal plants and all the regenerative potential of these different tissues. Material and Methods: A detailed review of the literature through the various search engines: Scopus, PubMed, google scholar, Cochrane, etc., uses the selected keywords to explore the effect of the regenerative potential of several medicinal plants. Results: Through our research, we have proceeded to sort different medicinal plants, according to their repairing and regenerative potential on the different tissues of the oral cavity. Conclusion: Future studies are conceivable to explore the opportunities and potential provided by medicinal plants in the field of regenerative dentistry.

Biomaterials and tissue engineering in traumatic brain injury:novel perspectives on promoting neural regeneration

Traumatic brain injury is a serious medical condition that can be attributed to falls, motor vehicle accidents, sports injuries and acts of violence, causing a series of neural injuries and neuropsychiatric symptoms. However, limited accessibility to the injury sites, complicated histological and anatomical structure, intricate cellular and extracellular milieu, lack of regenerative capacity in the native cells, vast variety of damage routes, and the insufficient time available for treatment have restricted the widespread application of several therapeutic methods in cases of central nervous system injury. Tissue engineering and regenerative medicine have emerged as innovative approaches in the field of nerve regeneration. By combining biomaterials, stem cells, and growth factors, these approaches have provided a platform for developing effective treatments for neural injuries, which can offer the potential to restore neural function, improve patient outcomes, and reduce the need for drugs and invasive surgical procedures. Biomaterials have shown advantages in promoting neural development, inhibiting glial scar formation, and providing a suitable biomimetic neural microenvironment, which makes their application promising in the field of neural regeneration. For instance, bioactive scaffolds loaded with stem cells can provide a biocompatible and biodegradable milieu. Furthermore, stem cells-derived exosomes combine the advantages of stem cells, avoid the risk of immune rejection, cooperate with biomaterials to enhance their biological functions, and exert stable functions, thereby inducing angiogenesis and neural regeneration in patients with traumatic brain injury and promoting the recovery of brain function. Unfortunately, biomaterials have shown positive effects in the laboratory, but when similar materials are used in clinical studies of human central nervous system regeneration, their efficacy is unsatisfactory. Here, we review the characteristics and properties of various bioactive materials, followed by the introduction of applications based on biochemistry and cell molecules, and discuss the emerging role of biomaterials in promoting neural regeneration. Further, we summarize the adaptive biomaterials infused with exosomes produced from stem cells and stem cells themselves for the treatment of traumatic brain injury. Finally, we present the main limitations of biomaterials for the treatment of traumatic brain injury and offer insights into their future potential.

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.

Healing Effect of the Extract of Kombucha in Male Wistar Rats

In order to assess the impact of the early and late tissue repair of Kombucha extract on incised wounds in animal models, 24 Wistar male rats were used and divided into three groups: one of the groups received a topical cure on the wound with Brosin, and the other received the Kombucha extract. The third group did not receive any treatment, working as a control group. The objective was to evaluate and compare the Kombucha extract with a commercial healing product. Each one of the animals took a 1 cm wound in depth and length at a femur level on a side of the left thigh. The healing process was evaluated on an early and late phase by performing a morphometric and morphological analysis under the assumption of a faster recovery with the use of Kombucha. The results showed that there was a poor recovery in the control group. On the other hand, the other two groups, Brosin and Kombucha, were similar, with little inflammation and a high cell proliferation and migration along with basal array pulls of elastin and collagen which served for angiogenesis, repair and renovation of the new tissue.

A Two-Dimensional Mathematical Model to Analyze Thermal Variations in Skin and Subcutaneous Tissue Region of Human Limb during Surgical Wound Healing

During wound healing, the metabolic activity associated with each phase must occur in the proper sequence, at a specific time, and continue for a specific duration at an optimal intensity. Any disturbance in appropriate thermal environment may complicate the wound healing process and may give rise to wound infection. In the presented paper a transient state two-dimensional mathematical model has been developed to analyse thermal variations in skin and subcutaneous tissue (SST) region of human limb. Due to circular shape of human limb, model has been developed in polar coordinates. The domain of the study consists of two types of tissues: abnormal tissues and normal tissues. The post surgery peripheral tissue of human limb during healing time is considered as abnormal tissues. The effect of variable density of blood vessels in dermal layer of both tissues on the physical and physiological parameters is incorporated in the model. The effect of healing on physiological parameters of abnormal tissue is incorporated by considering the physiological parameters to be function of time “t”. The effect of different climatic conditions is considered in the model. Taking into account the variable core temperature due to anatomy of arteries and variable physiological parameters in dermal layer of peripheral region, the well known Pennes’ bio heat equation is used to analyse the time-dependent temperature distribution of both normal and abnormal tissues. Comparison between temperature profiles of both normal and abnormal tissue has been done using finite element approach with bilinear shape functions in polar coordinates. A computer program in MATLAB has been developed to simulate the results.

Effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury

To study the effect of mild hypothermia on glucose metabolism and glycerol of brain tissue in patients with severe traumatic brain injury (sTBI).Methods All 33 patients with sTBI(GCS≤8) were randomly divided into hypothermic group and control group.Microdialysis catheters were inserted into the cerebral cortex of perilesion,relative normal brain tissue and subcutaneous tissue of abdomen in order to analyze the concentrations of lactate/pyruvate (L/P),lactate/glucose (L/G) and the glycerol(Gly) in extracellular fluid (ECF).Results In comparison with the control group,the concentration of L/G,L/P and Gly in periphery and that of L/P in ECF of the “normal brain tissue” were significantly decreased in the hypothermic group.In control group,concentration of L/G,L/P and Gly in periphery were higher than those in relative normal brain.In the hypothermic group,L/P concentration in periphery was higher than that in relative normal brain.Conclusion Mild hypothermia protects brain by decreasing concentrations of L/G,L/P and Gly in periphery and L/P concentration in “normal brain tissue”.The energy crisis and membrane phospholipid breakage in periphery are easier to happen after TBI,where mild hypothermia exerts significant protgective role.12 refs,3 tabs.

Collagen-chitosan scaffold impregnated with bone marrow mesenchymal stem cells for treatment of traumatic brain injury

Combinations of biomaterials and cells can effectively target delivery of cells or other therapeutic factors to the brain to rebuild damaged nerve pathways after brain injury.Porous collagen-chitosan scaffolds were prepared by a freeze-drying method based on brain tissue engineering.The scaffolds were impregnated with rat bone marrow mesenchymal stem cells.A traumatic brain injury rat model was established using the 300 g weight free fall impact method.Bone marrow mesenchymal stem cells/collagen-chitosan scaffolds were implanted into the injured brain.Modified neurological severity scores were used to assess the recovery of neurological function.The Morris water maze was employed to determine spatial learning and memory abilities.Hematoxylin-eosin staining was performed to measure pathological changes in brain tissue.Immunohistochemistry was performed for vascular endothelial growth factor and for 5-bromo-2-deoxyuridine(BrdU)/neuron specific enolase and BrdU/glial fibrillary acidic protein.Our results demonstrated that the transplantation of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds to traumatic brain injury rats remarkably reduced modified neurological severity scores,shortened the average latency of the Morris water maze,increased the number of platform crossings,diminished the degeneration of damaged brain tissue,and increased the positive reaction of vascular endothelial growth factor in the transplantation and surrounding areas.At 14 days after transplantation,increased BrdU/glial fibrillary acidic protein expression and decreased BrdU/neuron specific enolase expression were observed in bone marrow mesenchymal stem cells in the injured area.The therapeutic effect of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds was superior to stereotactic injection of bone marrow mesenchymal stem cells alone.To test the biocompatibility and immunogenicity of bone marrow mesenchymal stem cells and collagen-chitosan scaffolds,immunosuppressive cyclosporine was intravenously injected 12 hours before transplantation and 1-5 days after transplantation.The above indicators were similar to those of rats treated with bone marrow mesenchymal stem cells and collagen-chitosan scaffolds only.These findings indicate that transplantation of bone marrow mesenchymal stem cells in a collagen-chitosan scaffold can promote the recovery of neuropathological injury in rats with traumatic brain injury.This approach has the potential to be developed as a treatment for traumatic brain injury in humans.All experimental procedures were approved by the Institutional Animal Investigation Committee of Capital Medical University,China(approval No.AEEI-2015-035)in December 2015.

Remodeling of skin nerve fibers during burn wound healing

Burn wound healing involves a complex sequence of processes. Recent studies have revealed that skin reinnervation may have an impact on physiological wound repair. Few studies have addressed the process of reinnervation and morphological changes in regenerated nerve fibers. The regeneration of neurites during full-thickness burn wound healing was determined by immunofluorescent staining using an anti-neurofilament protein monoclonal antibody, and three-dimensional morphology was observed under a laser scanning confocal microscope. Morphology and the volume fraction of collagen and nerve fibers were measured. Skin reinnervation increased during wound healing, peaked during the proliferative scar stage, and then decreased to lower levels during the maturation period. The results from the skin nerve fibers correlated with those from collagen using semi-quantitative analysis. Disintegration and fragmentation were observed frequently in samples from the proliferative stage, and seldom occurred during the maturation stage. There was a remodeling process of regenerated nerve fibers during wound healing, which comprised changed innervation density and topical morphology. The mechanism of remodeling for nerve fibers requires further investigation.

Bioinspired Injectable Self-Healing Hydrogel Sealant with Fault-Tolerant and Repeated Thermo-Responsive Adhesion for Sutureless Post-Wound-Closure and Wound Healing

Hydrogels with multifunctionalities,including sufficient bonding strength,injectability and self-healing capacity,responsive-adhesive ability,fault-tolerant and repeated tissue adhesion,are urgently demanded for invasive wound closure and wound healing.Motivated by the adhesive mechanism of mussel and brown algae,bioinspired dynamic bonds cross-linked multifunctional hydrogel adhesive is designed based on sodium alginate(SA),gelatin(GT)and protocatechualdehyde,with ferric ions added,for sutureless post-wound-closure.The dynamic hydrogel cross-linked through Schiff base bond,catechol-Fe coordinate bond and the strong interaction between GT with temperature-dependent phase transition and SA,endows the resulting hydrogel with sufficient mechanical and adhesive strength for efficient wound closure,injectability and self-healing capacity,and repeated closure of reopened wounds.Moreover,the temperature-dependent adhesive properties endowed mispositioning hydrogel to be removed/repositioned,which is conducive for the fault-tolerant adhesion of the hydrogel adhesives during surgery.Besides,the hydrogels present good biocompatibility,near-infrared-assisted photothermal antibacterial activity,antioxidation and repeated thermo-responsive reversible adhesion and good hemostatic effect.The in vivo incision closure evaluation demonstrated their capability to promote the post-wound-closure and wound healing of the incisions,indicating that the developed reversible adhesive hydrogel dressing could serve as versatile tissue sealant.

Reducing intrathecal pressure after traumatic spinal cord injury: a potential clinical target to promote tissue survival

Spinal cord injury （SCI） is an unexpected event that is both devastating and debilitating, resulting in not just motor and sensory loss, but also autonomic dysfunction of the bladder, bowel and sexual organs. Currently, there are no treatments available to improve outcome follow- ing SCI, leaving individuals with permanent and lifelong physical disability. Worldwide it is estimated that more than 500,000 people sustain a SCI each year, with average lifetime cost of paraplegia and quadriplegia estimated at $5 million and $9.5 million respectively. We therefore urgently need effective therapies to improve quality of life following SCI, and this requires a greater understanding of how cell and axonal injury develops after the traumatic event.

Interplay of SOX transcription factors and microRNAs in the brain under physiological and pathological conditions

Precise tuning of gene expression,accomplished by regulato ry networks of transcription factors,epigenetic modifiers,and microRNAs,is crucial for the proper neural development and function of the brain cells.The SOX transcription factors are involved in regulating diverse cellular processes during embryonic and adult neurogenesis,such as maintaining the cell stemness,cell prolife ration,cell fate decisions,and terminal diffe rentiation into neurons and glial cells.MicroRNAs represent a class of small non-coding RNAs that play important roles in the regulation of gene expression.Together with other gene regulatory factors,microRNAs regulate different processes during neurogenesis and orchestrate the spatial and temporal expression important for neurodevelopment.The emerging data point to a complex regulatory network between SOX transcription factors and microRNAs that govern distinct cellular activities in the developing and adult brain.Deregulated SOX/mic roRNA interplay in signaling pathways that influence the homeostasis and plasticity in the brain has been revealed in various brain pathologies,including neurodegenerative disorders,traumatic brain injury,and cancer.Therapeutic strategies that target SOX/microRNA interplay have emerged in recent years as a promising tool to target neural tissue regeneration and enhance neuro restoration.N umerous studies have confirmed complex intera ctions between microRNAs and SOX-specific mRNAs regulating key features of glioblastoma.Keeping in mind the crucial roles of SOX genes and microRNAs in neural development,we focus this review on SOX/microRNAs interplay in the brain during development and adulthood in physiological and pathological conditions.Special focus was made on their interplay in brain pathologies to summarize current knowledge and highlight potential future development of molecular therapies.

Natural Nanoskin ACT Management of the Rare Disease as Burnt Patient with Epidermolysis Bullosa and Stevens-Johnson

Epidermolysis Bullosa (EB) is a group of rare genetic skin conditions, which is characterised by extremely fragile skin and recurrent blister formation, resulting from minor mechanical friction or trauma. Sufferers of EB have compared the sores to third-degree burns. Stevens-Johnson syndrome is a rare but very serious skin problem, which causes the appearance of reddish lesions throughout the body and other changes, such as difficulty in breathing and fever, which can endanger the life of the affected person. The aim of this study was to show efficacy of a NANOSKIN ACT, AND NANOSKIN ACT SOFT wound dressing on the wound care management in patients with EB AND Stevens-Johnson syndrome (SJS).

Acellular Amniotic Membrane Patch Regeneration for Burn Injury: The Future for Wound Healing

Acellular amniotic membrane (AAM) is a biodegradable and biocompatible natural that has a wide range of applications in the field of pharmaceutics, biomedical, chemical and cosmetics industry. One of the most interesting characteristics of AAM is its antibacterial and anti-inflammatory, anti-angiogenic, anti-fibrosis activity is an attractive approach for treating inflammatory disorders, wounds, and burns. The isolated use of AAM may not be sufficient to produce an adequate anti-inflammatory and antimicrobial effect to fulfill different purposes, has attracted considerable attention that has similar properties to the native tissues. This mini-review offers a focuses on modern aspects of the biomaterials, growth factors, biocompatibility, and acellular matrix which are the basic elements for use in the tissue regeneration and replacement after an injury.

Role of defensins in diabetic wound healing

The adverse consequences resulting from diabetes are often presented as severe complications.Diabetic wounds are one of the most commonly occurring complications in diabetes,and the control and treatment of this is costly.Due to a series of pathophysiological mechanisms,diabetic wounds remain in the inflammatory phase for a prolonged period of time,and face difficulty in entering the proliferative phase,thus leading to chronic non-healing wounds.The current consensus on the treatment of diabetic wounds is through multidisciplinary comprehensive management,however,standard wound treatment methods are still limited and therefore,more effective methods are required.In recent years,defensins have been found to play diverse roles in a variety of diseases;however,the molecular mechanisms underlying these activities are still largely unknown.Defensins can be constitutively or inductively produced in the skin,therefore,their local distribution is affected by the microenvironment of these diabetic wounds.Current evidence suggests that defensins are involved in the diabetic wound pathogenesis,and can potentially promote the early completion of each stage,thus making research on defensins a promising area for developing novel treatments for diabetic wounds.In this review,we describe the complex function of human defensins in the development of diabetic wounds,and suggest potential therapeutic benefits.

Erbium-doped yttrium aluminum garnet laser and advanced plateletrich fibrin+in periodontal diseases:Two case reports and review of the literature

BACKGROUND The goal of periodontal disease treatment is to completely remove bacteria and promote wound healing.The erbium-doped yttrium aluminum garnet(Er:YAG)laser is commonly used to treat periodontal disease.Advanced platelet-rich fibrin+(A-PRF+)secrets growth factors that accelerates soft-and hard-tissue regeneration and wound healing.Herein I present 2 cases of patients with oral diseases treated with a combination of Er:YAG laser and A-PRF+.CASE SUMMARY Case 1 was a female with pocket depth bone loss over 8 mm and infection of tooth 31 and 41,and severe advanced periodontitis with grade III mobility.Case 2 was a male with tooth 22 root end apical swelling and infection and alveolar bony defects.Clinical outcomes were recorded at 6 and 36 mo.In case 1,the Er:YAG laser was used to perform open flap debridement(100 mJ/pulse,15 Hz)and remove calculus and granulation tissue(50 mJ/pulse,30 Hz).In case 2 the laser was used to create a semilunar full thickness flap incision(80 mJ/pulse,20 Hz)and eliminate the pathogen(100 mJ/pulse,15 Hz).In both patients,A-PRF+mixed with bone was used to fill bone defects,and A-PRF+autologous membranes were used to cover tension-free primary flaps.There was no recurrent infection at 36 mo,and tissue regeneration and would healing occurred.CONCLUSION Debridement with an Er:YAG laser followed by treatment with A-PRF+is effective for the treatment periodontal diseases with bone defects.

AB089.Impact of WNK1 inhibition on corneal wound healing using a model of human tissue-engineered cornea

Background:Because of its superficial anatomical localization,the cornea is particularly vulnerable to abrasive forces and various traumas,which can lead to significant visual impairments.Upon injury of the corneal epithelium,there are important changes that occur in the composition of the underlying extracellular matrix(ECM).Those changes are perceived by the integrins that recognize the ECM components as their ligand and activate different intracellular signalling pathways,ultimately leading to reepithelialisation and reorganization of the injured epithelium,both of which are necessary in order to restore the visual properties of the cornea.The goal of this study was to analyse the impact of the pharmacological inhibition of specific signal transduction mediators of integrin-dependant signalling pathways on corneal wound healing using both monolayers of hCECs and tissue-engineered human corneas(hTECs)as in vitro models.Methods:hTECs were produced by the self-assembly approach and wounded with a 8-mm diameter biopsy punch.Total RNA and proteins were isolated from the wounded and unwounded hTECs to conduct gene profiling analyses and protein kinase arrays.The wounded tissues were then incubated with the WNK1 inhibitor WNK463 and wound healing was monitored over a period of 6 days.Control corneas were incubated with the vehicle alone(DMSO).The impact of WNK1 inhibition on hCECs monolayers was determined using a scratch wound assay.Results:Gene profiling analyses and protein kinases arrays revealed important alterations in the expression and activity of several mediators from the integrin-dependent signalling pathways in response to the ECM changes taking place during corneal wound healing.Among these,WNK1 is considerably activated through phosphorylation during corneal wound healing.The pharmacological inhibition of WNK1 by WNK463 significantly reduced the dynamic of corneal wound closure in our hTECs and hCECs monolayers compared to their respective negative controls.Conclusions:These results allowed the identification of WNK1 kinase as an important player for a proper healing of the cornea.Also,these results allowed for a better understanding of the cellular and molecular mechanisms involved in corneal wound healing and they may lead to the identification of new therapeutic targets in the field of corneal wounds.

Adiponectin as a therapeutic target for diabetic foot ulcer

The global burden of diabetic foot ulcers(DFUs)is a significant public health concern,affecting millions of people worldwide.These wounds cause considerable suffering and have a high economic cost.Therefore,there is a need for effective strategies to prevent and treat DFUs.One promising therapeutic approach is the use of adiponectin,a hormone primarily produced and secreted by adipose tissue.Adiponectin has demonstrated anti-inflammatory and antiatherogenic properties,and researchers have suggested its potential therapeutic applications in the treatment of DFUs.Studies have indicated that adiponectin can inhibit the production of pro-inflammatory cytokines,increase the production of vascular endothelial growth factor,a key mediator of angiogenesis,and inhibit the activation of the intrinsic apoptotic pathway.Additionally,adiponectin has been found to possess antioxidant properties and impact glucose metabolism,the immune system,extracellular matrix remodeling,and nerve function.The objective of this review is to summarize the current state of research on the potential role of adiponectin in the treatment of DFUs and to identify areas where further research is needed in order to fully understand the effects of adiponectin on DFUs and to establish its safety and efficacy as a treatment for DFUs in the clinical setting.This will provide a deeper understanding of the underlying mechanisms of DFUs that can aid in the development of new and more effective treatment strategies.