Recent Advancements in the Development of Self Healing Concrete-A Systematic Review

Mechanical as well as durability properties are pivotal for any type of concrete which gets adversely affected due to cracks that may form due to loading beyond its capacity.Concrete has the intrinsic property to heal itself to some extent but not fully as the passive form of autogenous healing plays an inferior role for a complete repair of a cementitious material.The self-healing capabilities can be enhanced by adding chemical admixtures,polymers,and bacteria strains induced calcium carbonate precipitation,etc.In this paper,the advancements in the development and performance of self-healing concrete using chemical admixtures,polymers,and bacteria strains are reviewed.This systematic review includes the available experimental tests and methodologies investigating self-healing efficiency over the last decade.Further,this review focussed on self-healing materials,the ideology,and opinions of those in the construction field on the direction of self-healing concrete for future applications.It is yet not possible to predict the most appropriate technique,however,a generalized opinion about the effectiveness of the different approaches has been illustrated.

Fecal calprotectin and endoscopic scores: The cornerstones in clinical practice for evaluating mucosal healing in inflammatory bowel disease

Managing inflammatory bowel disease(IBD)is becoming increasingly complex and personalized,considering the advent of new advanced therapies with distinct mechanisms of action.Achieving mucosal healing(MH)is a pivotal therapeutic goal in IBD management and can prevent IBD progression and reduce flares,hospitalization,surgery,intestinal damage,and colorectal cancer.Employing proactive disease and therapy assessment is essential to achieve better control of intestinal inflammation,even if subclinical,to alter the natural course of IBD.Periodic monitoring of fecal calprotectin(FC)levels and interval endoscopic evaluations are cornerstones for evaluating response/remission to advanced therapies targeting IBD,assessing MH,and detecting subclinical recurrence.Here,we comment on the article by Ishida et al Moreover,this editorial aimed to review the role of FC and endoscopic scores in predicting MH in patients with IBD.Furthermore,we intend to present some evidence on the role of these markers in future targets,such as histological and transmural healing.Additional prospective multicenter studies with a stricter MH criterion,standardized endoscopic and histopathological analyses,and virtual chromoscopy,potentially including artificial intelligence and other biomarkers,are desired.

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.

Porous nanofibrous dressing enables mesenchymal stem cell spheroid formation and delivery to promote diabetic wound healing

Delayed and nonhealing of diabetic wounds imposes substantial economic burdens and physical pain on patients.Mesenchymal stem cells(MSCs)promote diabetic wound healing.Particularly when MSCs aggregate into multicellular spheroids,their therapeutic effect is enhanced.However,traditional culture platforms are inadequate for the efficient preparation and delivery of MSC spheroids,resulting in inefficiencies and inconveniences in MSC spheroid therapy.In this study,a three-dimensional porous nanofibrous dressing(NFD)is prepared using a combination of electrospinning and homogeneous freeze-drying.Using thermal crosslinking,the NFD not only achieves satisfactory elasticity but also maintains notable cytocompatibility.Through the design of its structure and chemical composition,the NFD allows MSCs to spontaneously form MSC spheroids with controllable sizes,serving as MSC spheroid delivery systems for diabetic wound sites.Most importantly,MSC spheroids cultured on the NFD exhibit improved secretion of vascular endothelial growth factor,basic fibroblast growth factor,and hepatocyte growth factor,thereby accelerating diabetic wound healing.The NFD provides a competitive strategy for MSC spheroid formation and delivery to promote diabetic wound healing.

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.

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.

Regulatory T cells in skin regeneration and wound healing

As the body’s integumentary system,the skin is vulnerable to injuries.The subsequent wound healing processes aim to restore dermal and epidermal integrity and functionality.To this end,multiple tissue-resident cells and recruited immune cells cooperate to efficiently repair the injured tissue.Such temporally-and spatially-coordinated interplay necessitates tight regulation to prevent collateral damage such as overshooting immune responses and excessive inflammation.In this context,regulatory T cells(Tregs)hold a key role in balancing immune homeostasis and mediating cutaneous wound healing.A comprehensive understanding of Tregs’multifaceted field of activity may help decipher wound pathologies and,ultimately,establish new treatment modalities.Herein,we review the role of Tregs in orchestrating the regeneration of skin adnexa and catalyzing healthy wound repair.Further,we discuss how Tregs operate during fibrosis,keloidosis,and scarring.

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].

Spatio-temporal dynamics of phytohormones in the tomato graft healing process

Graft healing involves a series of cytological and molecular events including wound responses, callus formation and vascular bundle remodelling. Hormones are important signalling molecules regulating plant development and responses to environmental stimuli. However,the detailed dynamics of phytohormones in graft healing remain elusive. In this research, internodes above and below the graft site were harvested from 0 to 168 h after grafting(HAG), and liquid chromatography tandem mass spectrometry(LC-MS/MS) was used to determinate jasmonic acid, auxin, cytokinin, ethylene, salicylic acid, abscisic acid and gibberellin levels during the graft healing process. Uniform manifold approximation and projection(UMAP) and k-means analyses were performed to explore hormone spatio-temporal dynamics. We found the stage-specific and asymmetric accumulation of phytohormones in the tomato graft healing process. At the early healing stage(before vascular bundle reconnection), IAA, cZ, ABA, JA and SA mainly accumulated above the graft site, while tZ and ACC mainly accumulated below the graft site. MEIAA, ICAld and IP mainly accumulated at the later stage. Comminated with the healing process, we suggested that JA is mainly involved in wound responses, IAA is beneficial to the formation of callus and vascular cell development, tZ promotes cell division, and IP is linked to vascular bundle remodelling. In addition, expression of JA-related genes SlMYC2 and SlJAZ2, IAA-related gene SlIAA1, tZ-related genes SlHP2 and SlRR8, and IP-related gene SlRR9 correlated with hormone accumulation. The findings provide important information about the hormones and genes involved in the tomato graft healing process.

Age-related secretion of grancalcin by macrophages induces skeletal stem/progenitor cell senescence during fracture healing

Skeletal stem/progenitor cell(SSPC)senescence is a major cause of decreased bone regenerative potential with aging,but the causes of SSPC senescence remain unclear.In this study,we revealed that macrophages in calluses secrete prosenescent factors,including grancalcin(GCA),during aging,which triggers SSPC senescence and impairs fracture healing.Local injection of human rGCA in young mice induced SSPC senescence and delayed fracture repair.Genetic deletion of Gca in monocytes/macrophages was sufficient to rejuvenate fracture repair in aged mice and alleviate SSPC senescence.Mechanistically,GCA binds to the plexin-B2 receptor and activates Arg2-mediated mitochondrial dysfunction,resulting in cellular senescence.Depletion of Plxnb2 in SSPCs impaired fracture healing.Administration of GCA-neutralizing antibody enhanced fracture healing in aged mice.Thus,our study revealed that senescent macrophages within calluses secrete GCA to trigger SSPC secondary senescence,and GCA neutralization represents a promising therapy for nonunion or delayed union in elderly individuals.

αB-crystallin mini-peptides support corneal healing in vitro and in vivo in rabbit model

AIM:To evaluate if topical use of αB-crystallin minipeptides supports corneal healing following flap surgery.METHODS:Cultured corneal cells were treated with fluorescent taggedαB-crystallin mini-peptides to assess its internalization.Cultured corneal cells pre-treated with or without the mini-peptides were exposed to H_(2)O_(2) and cell viability was examined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide(MTT)assay.Elongation of neurites of cultured trigeminal neurones was examined following treatment either withαB-crystallin mini-peptides or protein.Cultured trigeminal neurones were pre-treated either with αB-crystallin mini-peptides or crystallin protein and exposed to H_(2)O_(2) and presence of beading in the dendrites and axons was assessed.Corneal flap surgery was conducted on rabbit cornea and treated topically either withαB-crystallin peptide(0.5 mg/mL thrice daily for 14d)or phosphate-buffered saline(PBS).Corneal healing was evaluated under slit-lamp biomicroscope,mRNA expression of inflammatory cytokines were assessed and the corneas were evaluated by histopathology.RESULTS:Internalization ofαB-crystallin mini-peptides was ascertained by the detection of fluorescence within the corneal cells.The MTT assay revealed that treatment withαB-crystallin mini-peptide reduced cell death induced by H_(2)O_(2) treatment.The mini-peptides did not influence the elongation of trigeminal neurites,but significantly(P<0.05)reduced beading in the neurites.In rabbit eye,the treated corneas showed reduced hyper-reflective zones(P<0.05)and suppression in the expression of inflammatory cytokines.Histopathological examination also revealed reduction of inflammatory response in treated corneas.CONCLUSION:TheαB-crystallin mini-peptides restrict the damage to corneal cells and neurons and aids in corneal healing.

Mesenchymal stem cells in wound healing:A bibliometric analysis as a powerful research tool

Bibliographic analysis is still very rarely used in experimental basic study papers.The comprehensive bibliometric analysis of scientific literature on research progress and challenges in stem cell therapy for diabetic chronic wounds,which was conducted in the work of Shi et al can be a case study and a source of valuable information for writing reviews and experimental papers in this field.Basic experimental studies on a role of mesenchymal stem cells(MSCs)in wound healing that are published in 2023-2024,such as Zhang et al in 2023,Hu et al in 2023,Wang et al in 2023 are certainly also subjects for applying this powerful tool to analyze current research,challenges and perspectives in this field.This is due to the fact that these studies have addressed a great variety of aspects of the application of MSCs for the treatment of chronic wounds,such as using both the cells themselves and their various products:Sponges,hydrogels,exosomes,and genetic constructions.Such a wide variety of directions in the field of study and biomedical application of MSCs requires a deep understanding of the current state of research in this area,which can be provided by bibliometric analysis.Thus,the use of such elements of bibliographic analysis as publication count by year and analysis of top-10 keywords calculated independently or cited from bibliometric analysis studies can be safely recommended for every basic study manuscripts,primarily for the“Introduction”section,and review.

Single-cell sequencing technology in diabetic wound healing:New insights into the progenitors-based repair strategies

Diabetes mellitus(DM),an increasingly prevalent chronic metabolic disease,is characterised by prolonged hyperglycaemia,which leads to long-term health consequences.Although much effort has been put into understanding the pathogenesis of diabetic wounds,the underlying mechanisms remain unclear.The advent of single-cell RNA sequencing(scRNAseq)has revolutionised biological research by enabling the identification of novel cell types,the discovery of cellular markers,the analysis of gene expression patterns and the prediction of develop-mental trajectories.This powerful tool allows for an in-depth exploration of pathogenesis at the cellular and molecular levels.In this editorial,we focus on progenitor-based repair strategies for diabetic wound healing as revealed by scRNAseq and highlight the biological behaviour of various healing-related cells and the alteration of signalling pathways in the process of diabetic wound healing.ScRNAseq could not only deepen our understanding of the complex biology of diabetic wounds but also identify and validate new targets for inter-vention,offering hope for improved patient outcomes in the management of this challenging complication of DM.

Biological scaffold as potential platforms for stem cells:Current development and applications in wound healing

Wound repair is a complex challenge for both clinical practitioners and researchers.Conventional approaches for wound repair have several limitations.Stem cell-based therapy has emerged as a novel strategy to address this issue,exhibiting significant potential for enhancing wound healing rates,improving wound quality,and promoting skin regeneration.However,the use of stem cells in skin regeneration presents several challenges.Recently,stem cells and biomaterials have been identified as crucial components of the wound-healing process.Combination therapy involving the development of biocompatible scaffolds,accompanying cells,multiple biological factors,and structures resembling the natural extracellular matrix(ECM)has gained considerable attention.Biological scaffolds encompass a range of biomaterials that serve as platforms for seeding stem cells,providing them with an environment conducive to growth,similar to that of the ECM.These scaffolds facilitate the delivery and application of stem cells for tissue regeneration and wound healing.This article provides a comprehensive review of the current developments and applications of biological scaffolds for stem cells in wound healing,emphasizing their capacity to facilitate stem cell adhesion,proliferation,differentiation,and paracrine functions.Additionally,we identify the pivotal characteristics of the scaffolds that contribute to enhanced cellular activity.

Macrophages:Key players in diabetic wound healing

In this editorial,we discuss the article by Wen et al published.Diabetic foot ulcers are prevalent and serious complications of diabetes,significantly impacting patients’quality of life and often leading to disability or death,thereby placing a heavy burden on society.Effective diabetic wound healing is hindered by an imbalance in macrophage polarization;many macrophages fail to transition from the pro-inflammatory M1 phenotype to the anti-inflammatory M2 phenotype,which is crucial for tissue remodelling and repair.The wound healing process is both dynamic and complex.Healthy M1 macrophages,which have strong phagocytic abilities,are vital during the inflammatory phase of diabetic wound healing.However,the failure to transition to M2 macrophages during the proliferative phase hinders wound healing.We anticipate the development of new therapies that can repair damaged M1 macrophages during the inflammatory phase and promote M2 macrophage polarization during the proliferative phase,thereby enhancing the overall healing process.

Pulp health and calcific healing of a complicated crown–root fracture with additional root fracture in a maxillary incisor: A case report

BACKGROUND Complicated crown–root fracture (CRF) involves severe injury to the crown, root,and pulp, and may be accompanied by multiple root fractures. The loss of a toothhas lifelong consequences for children and teenagers, but the maintenance of pulphealth and the calcific healing of multiple root fractures are rarely reported in theliterature.CASE SUMMARY This case reports healing of a permanent tooth with complicated crown–root andadditional root fractures, in which pulp health was maintained. A 10-year-old girlfell and fractured the root of her maxillary left central incisor at the cervical level.After the coronal fragment was repositioned, the tooth was splinted until thetooth was no longer mobile, 2 years later. Eight years after treatment, the toothhas remained asymptomatic with vital pulp and localized gingival overgrowth.Cone-beam computed tomography revealed not only calcified healing of the CRFbut also spontaneous healing in an additional undiagnosed root fracture. Thefracture line on the enamel could not be healed by hard tissue and formed agroove in the cervical crown. It was speculated that the groove was related to thelocalized gingival overgrowth.CONCLUSION This case provides a clinical perspective of the treatment of a tooth with acomplicated CRF and an additional root fracture.

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.

Value of negative pressure sealing drainage on wound healing of Gustilo IIIB and IIIC open fractures

BACKGROUND Gustilo III fractures have a high incidence and are difficult to treat.Patients often experience difficulty in wound healing.Negative pressure drainage technology can help shorten wound healing time and has positive value in improving patient prognosis.AIM To explore the clinical value of the negative pressure sealing drainage technique in wound healing of Gustilo IIIB and IIIC open fractures.METHODS Eighty patients with Gustilo IIIB and IIIC open fractures with skin and soft tissue injuries who were treated in the Second People’s Hospital of Dalian from March 2019 to December 2021 were selected as the research subjects.They were divided into a study group(n=40,healed with negative pressure closed drainage)and a control group(n=40,healed with conventional dressing changes)according to the variation in the healing they received.The efficacy of the clinical interventions,the variations in the regression indicators(time to wound healing,time to fracture healing,time to hospitalization),and the conversion and healing of bacterial wounds were compared 1-3 mo after the intervention.RESULTS The total effective rate of patients among the study group was 95.00%(38/40),which was notably higher than 75.00%(30/40)among the control group(P<0.05).The wound healing time,fracture healing time,and hospital stay of the patients in the study group was shorter than the control group(P<0.05).After the intervention,the negative bacterial culture at the wound site rate and wound healing rate of the patients among the study group increased compared to the control group(P<0.05).CONCLUSION Negative pressure sealing and drainage technology has a good therapeutic effect on patients with Gustilo IIIB and IIIC open fracture wounds with skin and soft tissue injury.It can notably enhance the wound healing rate and the negative rate of bacteria on the wound surface and help to speed up the recovery process of patients.

X-Paste improves wound healing in diabetes via NF-E2-related factor/HO-1 signaling pathway

BACKGROUND Diabetic foot ulcers(DFU),as severe complications of diabetes mellitus(DM),significantly compromise patient health and carry risks of amputation and mortality.AIM To offer new insights into the occurrence and development of DFU,focusing on the therapeutic mechanisms of X-Paste(XP)of wound healing in diabetic mice.METHODS Employing traditional Chinese medicine ointment preparation methods,XP combines various medicinal ingredients.High-performance liquid chromatography(HPLC)identified XP’s main components.Using streptozotocin(STZ)-induced diabetic,we aimed to investigate whether XP participated in the process of diabetic wound healing.RNA-sequencing analyzed gene expression differences between XP-treated and control groups.Molecular docking clarified XP’s treatment mechanisms for diabetic wound healing.Human umbilical vein endothelial cells(HUVECs)were used to investigate the effects of Andrographolide(Andro)on cell viability,reactive oxygen species generation,apoptosis,proliferation,and metastasis in vitro following exposure to high glucose(HG),while NF-E2-related factor-2(Nrf2)knockdown elucidated Andro’s molecular mechanisms.RESULTS XP notably enhanced wound healing in mice,expediting the healing process.RNA-sequencing revealed Nrf2 upregulation in DM tissues following XP treatment.HPLC identified 21 primary XP components,with Andro exhibiting strong Nrf2 binding.Andro mitigated HG-induced HUVECs proliferation,metastasis,angiogenic injury,and inflammation inhibition.Andro alleviates HG-induced HUVECs damage through Nrf2/HO-1 pathway activation,with Nrf2 knockdown reducing Andro’s proliferative and endothelial protective effects.CONCLUSION XP significantly promotes wound healing in STZ-induced diabetic models.As XP’s key component,Andro activates the Nrf2/HO-1 signaling pathway,enhancing cell proliferation,tubule formation,and inflammation reduction.

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.