Regenerative medicine strategies for chronic complete spinal cord injury

Spinal cord injury is a condition in which the parenchyma of the spinal cord is damaged by trauma or various diseases.While rapid progress has been made in regenerative medicine for spinal cord injury that was previously untreatable,most research in this field has focused on the early phase of incomplete injury.However,the majority of patients have chronic severe injuries;therefore,treatments for these situations are of fundamental importance.The reason why the treatment of complete spinal cord injury has not been studied is that,unlike in the early stage of incomplete spinal cord injury,there are various inhibitors of neural regeneration.Thus,we assumed that it is difficult to address all conditions with a single treatment in chronic complete spinal cord injury and that a combination of several treatments is essential to target severe pathologies.First,we established a combination therapy of cell transplantation and drug-releasing scaffolds,which contributes to functional recovery after chronic complete transection spinal cord injury,but we found that functional recovery was limited and still needs further investigation.Here,for the further development of the treatment of chronic complete spinal cord injury,we review the necessary approaches to the different pathologies based on our findings and the many studies that have been accumulated to date and discuss,with reference to the literature,which combination of treatments is most effective in achieving functional recovery.

Advances in clinical applications of bioceramics in the new regenerative medicine era

In this editorial,we comment on the hard and soft tissue applications of different ceramic-based scaffolds prepared by different mechanisms such as 3D printing,sol-gel,and electrospinning.The new concept of regenerative medicine relies on biomaterials that can trigger in situ tissue regeneration and stem cell recruitment at the defect site.A large percentage of these biomaterials is ceramic-based as they provide the essential requirements of biomaterial principles such as tailored multisize porosity,antibacterial properties,and angiogenic properties.All these previously mentioned properties put bioceramics on top of the hierarchy of biomaterials utilized to stimulate tissue regeneration in soft and hard tissue wounds.Multiple clinical applications registered the use of these materials in triggering soft tissue regeneration in healthy and diabetic patients such as bioactive glass nanofibers.The results were promising and opened new frontiers for utilizing these materials on a larger scale.The same results were mentioned when using different forms and formulas of bioceramics in hard defect regeneration.Some bioceramics were used in combination with other polymers and biological scaffolds to improve their regenerative and mechanical properties.All this progress will enable a larger scale of patients to receive such services with ease and decrease the financial burden on the government.

Emergence of the stromal vascular fraction and secretome in regenerative medicine

Recently,we read a mini-review published by Jeyaraman et al.The article explored the optimal methods for isolating mesenchymal stromal cells from adipose tissue-derived stromal vascular fraction(SVF).Key factors include tissue source,processing techniques,cell viability assessment,and the advantages/disadvantages of autologous vs allogeneic use.The authors emphasized the need for standardized protocols for SVF isolation,ethical and regulatory standards for cell-based therapy,and safety to advance mesenchymal stromal cell-based therapies in human patients.This manuscript shares our perspective on SVF isolation in canines.We discussed future directions to potentiate effective regenerative medicine therapeutics in human and veterinary medicine.

Regenerative Braking Energy Recovery System of Metro Train Based on Dual-Mode Power Management

In order to fully utilize the regenerative braking energy of metro trains and stabilize the metro DC traction busbar voltage,a hybrid regenerative braking energy recovery system with a dual-mode power management strategy is proposed.Firstly,the construction of the hybrid regenerative braking energy recovery system is explained.Then,based on the power demand of low-voltage load in metro stations,a dual-mode power management strategy is proposed to allocate the reference power of each system according to the different working conditions,and the control methods of each system are set.Finally,the correctness and effectiveness of the dual-mode strategy are verified through simulation,and the proposed braking energy utilization scheme is compared with other singleform utilization schemes.The results illustrate that the hybrid system with the dual-mode strategy can effectively recycle the regenerative braking energy of metro train and inhibit the busbar voltage fluctuation;the proposed braking energy utilization scheme has certain advantages on energy recovery and DC bus voltage stabilization compared with other single-form schemes;the proposed power management strategy can correctly allocate the reference power of each system with a lower construction cost.

Modified approach of regenerative treatment for distal intrabony defect beneath non-keratinized mucosa at terminal molar:A case report

BACKGROUND Intrabony defects beneath non-keratinized mucosa are frequently observed at the distal site of terminal molars.Consequently,the application of regenerative treatment using the modified wedge-flap technique is considered impractical for these specific dental conditions.CASE SUMMARY This article proposes a modified surgical procedure aimed at exposing the distal intrabony defect by making a vertical incision in the keratinized buccal gingiva.The primary objective is to maintain gingival flap stability,thereby facilitating periodontal regeneration.The described technique was successfully employed in a case involving the left mandibular second molar,which presented with an intrabony defect without keratinized gingiva at the distal site.In this case,an incision was made on the disto-buccal gingival tissue,creating a tunnel-like separation of the distal non-keratinized soft tissue to expose the intrabony defect.Subsequently,bone grafting and guided tissue regeneration surgeries were performed,resulting in satisfactory bone fill at 9 mo postoperatively.CONCLUSION This technique offers a regenerative opportunity for the intrabony defects beneath non-keratinized mucosa and is recommended for further research.

Role of immune relevant factors in regenerative processes of bone tissue: a bibliometric and visualized analysis

Background:There is a deficiency of bibliometric and visually represented analysis in research on the immunological related variables involved in bone tissue regeneration.Using bibliometric and visual analysis,this study sought to thoroughly examine the hotspots and future directions in the investigation of immunological important variables in bone tissue regeneration.Methods:The Web of Science Core Collection(WoSCC)database was searched and a collection of published works on the subject of immunological related factors in bone tissue regeneration between 2000 and 2021 was generated.The data chosen from the WoSCC were then subjected to a systematic bibliometric and visualized analysis using the online bibliometric analytics system,Apache ECharts,VOSviewer,Bibliographic Items Co-occurrence Matrix Builder 2.0,and Gcluto 1.0.Results:For this investigation,1,088 publications on the involvement of immune related components in bone tissue regeneration were chosen.Between 2000 and 2021,China maintained its supremacy in global research on the function of immune related components in bone tissue regeneration.Shanghai Jiao Tong University is the most productive institution.Biomaterials has published the most publications on the involvement of immune-related components in bone tissue regeneration.Xiao Y,Schmidt-Bleek K,and Ignatius A all played important roles in the study of immune-related variables in bone tissue regeneration.Research on the role of immune relevant factors in bone tissue regeneration has identified five hotspots:(1)macrophage-based immunomodulation on osteogenesis of mesenchymal stem cells(MSCs);(2)biomaterials for bone repair in bone tissue engineering;(3)osteoimmunomodulation mediated by inflammation and macrophages during bone healing;(4)osteoimmunomodulation in angiogenesis during bone regeneration;and(5)the effect of macrophage polarization regulated by bone tissue engineering on osteogenic differentiation of MSCs as bone tissue.Conclusion:This study represents the first-ever bibliometric and visualized examination of how immune factors contribute to bone tissue regeneration.The focus and forthcoming direction in bone regeneration research will be on macrophage-driven immunomodulation in the process of bone regeneration.

Extracellular vesicles:Emerged as a promising strategy for regenerative medicine

Cell transplantation therapy has certain limitations including immune rejection and limited cell viability,which seriously hinder the transformation of stem cellbased tissue regeneration into clinical practice.Extracellular vesicles(EVs)not only possess the advantages of its derived cells,but also can avoid the risks of cell transplantation.EVs are intelligent and controllable biomaterials that can participate in a variety of physiological and pathological activities,tissue repair and regeneration by transmitting a variety of biological signals,showing great potential in cell-free tissue regeneration.In this review,we summarized the origins and characteristics of EVs,introduced the pivotal role of EVs in diverse tissues regeneration,discussed the underlying mechanisms,prospects,and challenges of EVs.We also pointed out the problems that need to be solved,application directions,and prospects of EVs in the future and shed new light on the novel cell-free strategy for using EVs in the field of regenerative medicine.

Injectable hydrogel made from antler mesenchyme matrix for regenerative wound healing via creating a fetal-like niche

BACKGROUND Scar formation and loss of cutaneous appendages are the greatest challenges in cutaneous wound healing.Previous studies have indicated that antler reserve mesenchyme(RM)cells and their conditioned medium improved regenerative wound healing with partial recovery of cutaneous appendages.AIM To develop hydrogels from the antler RM matrix(HARM)and evaluate the effect on wound healing.METHODS We prepared the hydrogels from the HARM via enzymatic solubilization with pepsin.Then we investigated the therapeutic effects of HARM on a full-thickness cutaneous wound healing rat model using both local injections surrounding the wound and topical wound application.RESULTS The results showed that HARM accelerated wound healing rate and reduced scar formation.Also,HARM stimulated the regeneration of cutaneous appendages and blood vessels,and reduced collagen fiber aggregation.Further study showed that these functions might be achieved via creating a fetal-like niche at the wound site.The levels of fetal wound healing-related genes,including Collagen III and TGFβ3 treated with HARM were all increased,while the expression levels of Collagen I,TGFβ1,and Engrailed 1 were decreased in the healing.Moreover,the number of stem cells was increased in the fetal-like niche created by HARM,which may contribute to the regeneration of cutaneous appendages.CONCLUSION Overall,we successfully developed an injectable hydrogel made from antler RM matrix for the regenerative repair of full-thickness cutaneous wounds.We uncovered the molecular mechanism of the hydrogels in promoting regenerative wound healing,and thus pave the way for HARM to be developed for the clinic use.

Pitfalls and promises of bile duct alternatives:There is plenty of room in the regenerative surgery

Current abdominal surgery has several approaches for biliary reconstruction.However,the creation of functional and clinically applicable bile duct substitutes still represents an unmet need.In the paper by Miyazawa and colleagues,approaches to the creation of bile duct alternatives were summarized,and the reasons for the lack of development in this area were explained.The history of bile duct surgery since the nineteenth century was also traced,leading to the conclusion that the use of bioabsorbable materials holds promise for the creation of bile duct substitutes in the future.We suggest three ideas that may stimulate progress in the field of bile duct substitute creation.First,a systematic analysis of the causative factors leading to failure or success in the creation of bile duct substitutes may help to develop more effective approaches.Second,the regeneration of a bile duct is delicately balanced between epithelialization and subsequent submucosal maturation within limited time frames,which may be more apparent when using quantitative models to estimate outcomes.Third,the utilization of the organism’s endogenous regeneration abilities may enhance the creation of bile duct substitutes.We are convinced that an interdisciplinary approach,including quantitative methods,machine learning,and deep retrospective analysis of the causes that led to success and failure in studies on the creation of bile duct substitutes,holds great value.Additionally,more attention should be directed towards the balance of epithelialization and submucosal maturation rates,as well as induced angiogenesis.These ideas deserve further investigation to pave the way for bile duct restoration with physiologically relevant outcomes.

Regenerative peripheral nerve interface prevents neuroma formation after peripheral nerve transection

Neuroma formation after peripheral nerve transection often leads to severe neuropathic pain.Regenerative peripheral nerve interface has been shown to reduce painful neuroma in the clinic.However,no reports have investigated the underlying mechanisms,and no comparative animal studies on regenerative peripheral nerve interface and other means of neuroma prevention have been conducted to date.In this study,we established a rat model of left sciatic nerve transfection,and subsequently interfered with the model using the regenerative peripheral nerve interface or proximal nerve stump implantation inside a fully innervated muscle.Results showed that,compared with rats subjected to nerve stump implantation inside the muscle,rats subjected to regenerative peripheral nerve interface intervention showed greater inhibition of the proliferation of collagenous fibers and irregular regenerated axons,lower expressions of the fibrosis markerα-smooth muscle actin and the inflammatory marker sigma-1 receptor in the proximal nerve stump,lower autophagy behaviors,lower expressions of c-fos and substance P,higher expression of glial cell line-derived neurotrophic factor in the ipsilateral dorsal root ganglia.These findings suggested that regenerative peripheral nerve interface inhibits peripheral nerve injury-induced neuroma formation and neuropathic pain possibly via the upregulation of the expression of glial cell line-derived neurotrophic factor in the dorsal root ganglia and reducing neuroinflammation in the nerve stump.

Unleashing the healing potential:Exploring next-generation regenerative protein nanoscaffolds for burn wound recovery

Burn injury is a serious public health problem and scientists are continuously aiming to develop promising biomimetic dressings for effective burn wound management.In this study,a greater efficacy in burn wound healing and the associated mechanisms ofα-lactalbumin(ALA)based electrospun nanofibrous scaffolds(ENs)as compared to other regenerative protein scaffolds were established.Bovine serum albumin(BSA),collagen type I(COL),lysozyme(LZM)and ALA were separately blended with poly(ε-caprolactone)(PCL)to fabricate four different composite ENs(LZM/PCL,BSA/PCL,COL/PCL and ALA/PCL ENs).The hydrophilic composite scaffolds exhibited an enhancedwettability and variablemechanical properties.The ALA/PCL ENs demonstrated higher levels of fibroblast proliferation and adhesion than the other composite ENs.As compared to PCL ENs and other composite scaffolds,the ALA/PCL ENs also promoted a better maturity of the regenerative skin tissues and showed a comparable wound healing effect to Collagen sponge^(■)on third-degree burn model.The enhanced wound healing activity of ALA/PCL ENs compared to other ENs could be attributed to their ability to promote serotonin production at wound sites.Collectively,this investigation demonstrated that ALA is a unique protein with a greater potential for burn wound healing as compared to other regenerative proteins when loaded in the nanofibrous scaffolds.

A Review of Electromagnetic Energy Regenerative Suspension System&Key Technologies

The active suspension has undoubtedly improved the performance of the vehicle,however,the trend of“lowcarbonization,intelligence,and informationization”in the automotive industry has put forward higher and more urgent requirements for the suspension system.The automotive industry and researchers favor active energy regeneration suspension technology with safety,comfort,and high energy regenerative efficiency.In this paper,we review the research progress of the structure form,optimization method,and control strategy of electromagnetic energy regenerative suspension.Specifically,comparing the pros and cons of the existing technology in solving the contradiction between dynamic performance and energy regeneration.In addition,the development trend of electromagnetic energy regenerative suspension in the field of structure form,optimization method,and control technology prospects.

Energy Management of Networked Smart Railway Stations Considering Regenerative Braking, Energy Storage System, and Photovoltaic Units

The networking of microgrids has received significant attention in the form of a smart grid.In this paper,a set of smart railway stations,which is assumed as microgrids,is connected together.It has been tried to manage the energy exchanged between the networked microgrids to reduce received energy from the utility grid.Also,the operational costs of stations under various conditions decrease by applying the proposed method.The smart railway stations are studied in the presence of photovoltaic(PV)units,energy storage systems(ESSs),and regenerative braking strategies.Studying regenerative braking is one of the essential contributions.Moreover,the stochastic behaviors of the ESS’s initial state of energy and the uncertainty of PV power generation are taken into account through a scenario-based method.The networked microgrid scheme of railway stations(based on coordinated operation and scheduling)and independent operation of railway stations are studied.The proposed method is applied to realistic case studies,including three stations of Line 3 of Tehran Urban and Suburban Railway Operation Company(TUSROC).The rolling stock is simulated in the MATLAB environment.Thus,the coordinated operation of networked microgrids and independent operation of railway stations are optimized in the GAMS environment utilizing mixed-integer linear programming(MILP).

Regenerative Medicine: A Review of Solutions in the Treatment of Skin Defects

The issue of skin defects is a major concern of almost every trauma surgeon after surgery. Despite numerous conventional methods and introduction of the reconstruction ladder, managing skin defects is still a challenge for the trauma surgeons. In recent years, parallel to the advances in the more conventional methods of skin repair, regenerative medicine has offered new and novel treatments. This article aims to explore these contemporary regenerative solutions as well as to review the conventional methods of treating skin defects.

Regenerative Medicine in Orthopaedics: Microsurgery Achievements for Translational Animal Model

Purpose: Despite many scientific advances, Regenerative Medicine is still in the preclinical stages in many areas. In this article, we intend to discuss the role of microsurgery in the bench-to-bedside transition of such primary findings. Method: By searching the papers related to the history of Regenerative Medicine (RM) and the news of Tissue Engineering (TE) in orthopedics in Pubmed, Scopus, and Google Scholar databases, we accessed a complete archive of various topics related to this field. Result: We first assessed the history and achievements of regenerative medicine, then we realized the importance of translational medical sciences and the role of animal models in this incipient phenomenon. Finally, after mastering the capabilities of microsurgery and the useful contribution of this technique to the advancement of clinical applications of regenerative medicine in various branches such as skin, skeletal system, nerves, and blood vessels, we decided to express the gist of our studies through this article. Conclusion: Considering the widespread use of small animals in regenerative medicine projects and the inevitable role of microsurgery in performing the best intervention on these animal models, the significant progress of regenerative medicine clinical application requires special attention to microsurgery in associated research.

Burner effects on melting process of regenerative aluminum melting furnace

According to the features of melting process of regenerative aluminum melting furnaces, a three-dimensional mathematical model with user-developed melting model, burner reversing and burning capacity model was established. The numerical simulation of melting process of a regenerative aluminum melting furnace was presented using hybrid programming method of FLUENT UDF and FLUENT scheme based on the heat balance test. Burner effects on melting process of aluminum melting furnaces were investigated by taking optimization regulations into account. The change rules of melting time on influence factors are achieved. Melting time decreases with swirl number, vertical angle of burner, air preheated temperature or natural gas flow; melting time firstly decreases with horizontal angle between burners or air-fuel ratio, then increases; melting time increases with the height of burner.

A new braking force distribution strategy for electric vehicle based on regenerative braking strength continuity

Regenerative braking was the process of converting the kinetic energy and potential energy, which were stored in the vehicle body when vehicle braked or went downhill, into electrical energy and storing it into battery. The problem on how to distribute braking forces of front wheel and rear wheel for electric vehicles with four-wheel drive was more complex than that for electric vehicles with front-wheel drive or rear-wheel drive. In this work, the frictional braking forces distribution curve of front wheel and rear wheel is determined by optimizing the braking force distribution curve of hydraulic proportional-adjustable valve, and then the safety brake range is obtained correspondingly. A new braking force distribution strategy based on regenerative braking strength continuity is proposed to solve the braking force distribution problem for electric vehicles with four-wheel drive. Highway fuel economy test(HWFET) driving condition is used to provide the speed signals, the braking force equations of front wheel and rear wheel are expressed with linear equations. The feasibility, effectiveness, and practicality of the new braking force distribution strategy based on regenerative braking strength continuity are verified by regenerative braking strength simulation curve and braking force distribution simulation curves of front wheel and rear wheel. The proposed strategy is simple in structure, easy to be implemented and worthy being spread.

Non-cirrhotic portal hypertension with large regenerative nodules: A diagnostic challenge

Non-cirrhotic portal hypertension is a poorly understood condition characterized by portal hypertension in the absence of conventional hepatic cirrhosis and described in association with blood coagulation disorders, myeloproliferative and immunological diseases and with exposure to toxic drugs. Very recently, precise classification criteria have been proposed in order to define four distinct subcategories. The present case highlights how the clinical presentation, the confounding results from imaging studies, and the difficulties in the histological evaluation often render cases of non-cirrhotic portal hypertension a real diagnostic challenge. It also underscores the classification problems which can be faced once this diagnosis is performed. Indeed, the different subcategories proposed result from the prevalent subtypes in a spectrum of hepatic regenerative responses to a variety of injuries determining microcirculatory dis-turbances. More flexibility in classification should derive from this etiopathogenic background.

AUTOMATIC CONTROL OF REGENERATIVE CUTTING CHATTER BASED ON OPTIMAL REGULATION OF SPINDLE SPEED

An applicable method to control regenerative cutting chatter automatically based on the optimal regulation of spindle speed is introduced. The optimal value of the phase shift angle of the regenerative chatter signal between the two successive cuts is 270°. The cutting process can be adjusted from the unstable region to stable one whenever regenerative chatter occurs if the phase shift angle is kept 270° by the optimal regulation of spindle speed. The theoretical analysis and the experimental results prove that the optimal regulation of spindle speed can effectively control regenerative cutting chatter. In addition, a reliablelly optimal control system of reliable spindle speed is presented. There is no need for system identification of the machine tool, and it is easy to put this regenerative chatter control method into practice, so the method has excellent application prospect.

Role and prospects of regenerative biomaterials in the repair of spinal cord injury

Axonal junction defects and an inhibitory environment after spinal cord injury seriously hinder the regeneration of damaged tissues and neuronal functions. At the site of spinal cord injury, regenerative biomaterials can fill cavities, deliver curative drugs, and provide adsorption sites for transplanted or host cells. Some regenerative biomaterials can also inhibit apoptosis, inflammation and glial scar formation, or further promote neurogenesis, axonal growth and angiogenesis. This review summarized a variety of biomaterial scaffolds made of natural, synthetic, and combined materials applied to spinal cord injury repair. Although these biomaterial scaffolds have shown a certain therapeutic effect in spinal cord injury repair, there are still many problems to be resolved, such as product standards and material safety and effectiveness.