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.

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.

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.

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.

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.

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.

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).

Therapeutic potential of urine-derived stem cells in renal regeneration following acute kidney injury:A comparative analysis with mesenchymal stem cells

BACKGROUND Acute kidney injury(AKI)is a common clinical syndrome with high morbidity and mortality rates.The use of pluripotent stem cells holds great promise for the treatment of AKI.Urine-derived stem cells(USCs)are a novel and versatile cell source in cell-based therapy and regenerative medicine that provide advantages of a noninvasive,simple,and low-cost approach and are induced with high multidifferentiation potential.Whether these cells could serve as a potential stem cell source for the treatment of AKI has not been determined.METHODS Stem cell markers with multidifferentiation potential were isolated from human amniotic fluid.AKI severe combined immune deficiency(SCID)mice models were induced by means of an intramuscular injection with glycerol.USCs isolated from human-voided urine were administered via tail veins.The functional changes in the kidney were assessed by the levels of blood urea nitrogen and serum creatinine.The histologic changes were evaluated by hematoxylin and eosin staining and transferase dUTP nick-end labeling staining.Meanwhile,we compared the regenerative potential of USCs with bone marrow-derived mesenchymal stem cells(MSCs).RESULTS Treatment with USCs significantly alleviated histological destruction and functional decline.The renal function was rapidly restored after intravenous injection of 5×105 human USCs into SCID mice with glycerol-induced AKI compared with injection of saline.Results from secretion assays conducted in vitro demonstrated that both stem cell varieties released a wide array of cytokines and growth factors.This suggests that a mixture of various mediators closely interacts with their biochemical functions.Two types of stem cells showed enhanced tubular cell prolif-eration and decreased tubular cell apoptosis,although USC treatment was not more effective than MSC treatment.We found that USC therapy significantly improved renal function and histological damage,inhibited inflammation and apoptosis processes in the kidney,and promoted tubular epithelial proliferation.CONCLUSION Our study demonstrated the potential of USCs for the treatment of AKI,representing a new clinical therapeutic strategy.

Blended Regenerative Anti-Lock Braking System and Electronic Wedge Brake Coordinate Control Ensuring Maximal Energy Recovery and Stability of All-Wheel-Motor-Drive Electric Vehicles

ABS is an active safety system which showed a valuable contribution to vehicle safety and stability since it was first introduced. Recently, EVs with in-wheel-motors have drawn increasing attention owing to their greatest advantages. Wheels torques are precisely and swiftly controlled thanks to electric motors and their advanced driving techniques. In this paper, a regenerative-ABS control RABS is proposed for all-in-wheel-motors-drive EVs. The RABS is realized as a pure electronic braking system called brake-by-wire. A coordination strategy is suggested to control RABS compromising three layers. First, wheels slip control takes place, and braking torque is calculated in the higher layer. In the coordinate interlayer, torque is allocated between actuators ensuring maximal energy recovery and vehicle stability. While in the lower layer, actuator control is performed. The RABS effectiveness is validated on a 3-DOF EVSimulink model through two straight-line braking manoeuvres with low and high initial speeds of 50 km/h and 150 km/h, respectively. Both regular and emergency braking manoeuvres are considered with ABS enabled and disabled for comparison. Simulation results showed the high performance of the proposed RABS control in terms of vehicle stability, brake response, stopping distance, and battery re-charging.

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.

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.

Design and Analysis of Electro-mechanical Hybrid Anti-lock Braking System for Hybrid Electric Vehicle Utilizing Motor Regenerative Braking

Braking on low adhesion-coefficient roads, hybrid electric vehicle＇s motor regenerative torque is switched off to safeguard the normal anti-lock braking system （ABS） fimction. When the ABS control is terminated, the motor regenerative braking is readmitted. Aiming at avoiding permanent cycles from hydraulic anti-lock braking to motor regenerative braking, a novel electro-mechanical hybrid anti-lock braking system using fuzzy logic is designed. Different from the traditional single control structure, this system has a two-layered hierarchical structure, The first layer is responsible for harmonious adjustment or interaction between regenerative system and anti-lock braking system. The second layer is responsible for braking torque distribution and adjustment. The closed-loop simulation model is built. Control strategy and method for coordination between regenerative and anti-lock braking are developed. Simulation braking on low adhesion-coefficient roads with fuzzy logic control and real vehicle braking field test are presented. The results from simulating analysis and experiment show braking performance of the vehicle is perfect, harmonious coordination between regenerative and anti-lock braking function, significant amount of braking energy can be recovered and the proposed control strategy and method are effective.

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.

Advances in regenerative therapies for spinal cord injury:a biomaterials approach

Spinal cord injury results in the permanent loss of function, causing enormous personal, social and economic problems. Even though neural regeneration has been proven to be a natural mech- anism, central nervous system repair mechanisms are ineffective due to the imbalance of the inhibitory and excitatory factors implicated in neuroregeneration. Therefore, there is growing re- search interest on discovering a novel therapeutic strategy for effective spinal cord injury repair. To this direction, cell-based delivery strategies, biomolecule delivery strategies as well as scaf- fold-based therapeutic strategies have been developed with a tendency to seek for the answer to a combinatorial approach of all the above. Here we review the recent advances on regenerativel neural engineering therapies for spinal cord injury, aiming at providing an insight to the most promising repair strategies, in order to facilitate future research conduction.