Mesenchymal stem cells （MSCs） have great potential for treating various diseases, especially those related to tissue damage involving immune reactions. Various studies have demonstrated that MSCs are strongly immuno...Mesenchymal stem cells （MSCs） have great potential for treating various diseases, especially those related to tissue damage involving immune reactions. Various studies have demonstrated that MSCs are strongly immunosuppressive in vitro and in vivo. Our recent studies have shown that un-stimulated MSCs are indeed incapable of immunosuppression; they become potently immunosuppressive upon stimulation with the supernatant of activated lymphocytes, or with combinations of IFN-γ, with TNF-α, IL-1α or IL-1β. This observation revealed that under certain circumstances, inflammatory cytokines can actually become immunosuppressive. We showed that there is a species variation in the mechanisms of MSC-mediated immunosuppression： immunosuppression by cytokine-primed mouse MSCs is mediated by nitric oxide （NO）, whereas immunosuppression by cytokine-primed human MSCs is executed through indoleamine 2, 3-dioxygenase （IDO）. Additionally, upon stimulation with the inflammatory cytokines, both mouse and human MSCs secrete several leukocyte chemokines that apparently serve to attract immune cells into the proximity with MSCs, where NO or IDO is predicted to be most active. Therefore, immunosuppression by inflammatory cytokine-stimulated MSCs occurs via the concerted action of chemokines and immune-inhibitory NO or IDO produced by MSCs. Thus, our results provide novel information about the mechanisms of MSC-mediated immunosuppression and for better application of MSCs in treating tissue injuries induced by immune responses.展开更多
Bone tissue engineering(BTE)has proven to be a promising strategy for bone defect repair.Due to its excellent biological properties,gelatin methacrylate(GelMA)hydrogels have been used as bioinks for 3D bioprinting in ...Bone tissue engineering(BTE)has proven to be a promising strategy for bone defect repair.Due to its excellent biological properties,gelatin methacrylate(GelMA)hydrogels have been used as bioinks for 3D bioprinting in some BTE studies to produce scaffolds for bone regeneration.However,applications for load-bearing defects are limited by poor mechanical properties and a lack of bioactivity.In this study,3D printing technology was used to create nano-attapulgite(nano-ATP)/GelMA composite hydrogels loaded into mouse bone mesenchymal stem cells(BMSCs)and mouse umbilical vein endothelial cells(MUVECs).The bioprintability,physicochemical properties,and mechanical properties were all thoroughly evaluated.Our findings showed that nano-ATP groups outperform the control group in terms of printability,indicating that nano-ATP is beneficial for printability.Additionally,after incorporation with nano-ATP,the mechanical strength of the composite hydrogels was significantly improved,resulting in adequate mechanical properties for bone regeneration.The presence of nano-ATP in the scaffolds has also been stud-ied for cell-material interactions.The findings show that cells within the scaffold not only have high viability but also a clear proclivity to promote osteogenic differentiation of BMSCs.Besides,the MUVECs-loaded composite hydrogels demonstrated increased angiogenic activity.A cranial defect model was also developed to evaluate the bone repair capability of scaffolds loaded with rat BMSCs.According to histo-logical analysis,cell-laden nano-ATP composite hydrogels can effectively im prove bone regeneration and promote angiogenesis.This study demonstrated the potential of nano-ATP for bone tissue engineering,which should also increase the clinical practicality of nano-ATP.展开更多
Schwann cells are glial cells of peripheral nervous system, responsible for axonal myelination and ensheathing, as well as tissue repair following a peripheral nervous system injury. They are one of several cell types...Schwann cells are glial cells of peripheral nervous system, responsible for axonal myelination and ensheathing, as well as tissue repair following a peripheral nervous system injury. They are one of several cell types that are widely studied and most commonly used for cell transplantation to treat spinal cord injury, due to their intrinsic characteristics including the ability to secrete a variety of neurotrophic factors. This mini review summarizes the recent findings of endogenous Schwann cells after spinal cord injury and discusses their role in tissue repair and axonal regeneration. After spinal cord injury, numerous endogenous Schwann cells migrate into the lesion site from the nerve roots, involving in the construction of newly formed repaired tissue and axonal myelination. These invading Schwann cells also can move a long distance away from the injury site both rostrally and caudally. In addition, Schwann cells can be induced to migrate by minimal insults （such as scar ablation） within the spinal cord and integrate with astrocytes under certain circumstances. More importantly, the host Schwann cells can be induced to migrate into spinal cord by transplantation of different cell types, such as exogenous Schwann cells, olfactory ensheathing cells, and bone marrow-derived stromal stem cells. Migration of endogenous Schwann cells following spinal cord injury is a common natural phenomenon found both in animal and human, and the myelination by Schwann cells has been examined effective in signal conduction electrophysiologically. Therefore, if the inherent properties of endogenous Schwann cells could be developed and utilized, it would offer a new avenue for the restoration of injured spinal cord.展开更多
Neurological disorders are diseases of the central and peripheral nervous systems.These disorders include Alzheimer＇s disease,epilepsy,brain tumor,and cerebrovascular diseases（stroke,migraine and other headache diso...Neurological disorders are diseases of the central and peripheral nervous systems.These disorders include Alzheimer＇s disease,epilepsy,brain tumor,and cerebrovascular diseases（stroke,migraine and other headache disorders,multiple sclerosis,Parkinson＇s disease,and neuroinfections）.展开更多
BACKGROUND Laparoscopic sacrocolpopexy for pelvic organ prolapse(POP)is a new and widely used approach;however,ever since the United States Food and Drug Administration warned against the use of surgical mesh,repairs ...BACKGROUND Laparoscopic sacrocolpopexy for pelvic organ prolapse(POP)is a new and widely used approach;however,ever since the United States Food and Drug Administration warned against the use of surgical mesh,repairs performed using patients’tissues[i.e.native tissue repair(NTR)]instead of mesh have attracted much attention.At our hospital,laparoscopic sacrocolpopexy(the Shull method)was introduced in 2017.However,patients with more severe POP who have a long vaginal canal and overextended uterosacral ligaments may not be candidates for this procedure.AIM To validate a new NTR treatment for POP,we examined patients undergoing laparoscopic vaginal stump–round ligament fixation(the Kakinuma method).METHODS The study patients were 30 individuals with POP who underwent surgery using the Kakinuma method between January 2020 and December 2021 and who were followed up for>12 mo after surgery.We retrospectively examined surgical outcomes for surgery duration,blood loss,intraoperative complications,and incidence of recurrence.The Kakinuma method involves round ligament suturing and fixation on both sides,effectively lifting the vaginal stump after laparoscopic hysterectomy.RESULTS The patients’mean age was 66.5±9.1(45-82)years,gravidity was 3.1±1.4(2-7),parity was 2.5±0.6(2-4)times,and body mass index was 24.5±3.3(20.9-32.8)kg/m2.According to the POP quantification stage classification,there were 8 patients with stage Ⅱ,11 with stage Ⅲ,and 11 with stage Ⅳ.The mean surgery duration was 113.4±22.6(88-148)min,and the mean blood loss was 26.5±39.7(10-150)mL.There were no perioperative complications.None of the patients exhibited reduced activities of daily living or cognitive impairment after hospital discharge.No cases of POP recurrence were observed 12 mo after the operation.CONCLUSION The Kakinuma method,similar to conventional NTR,may be an effective treatment for POP.展开更多
Functional repair of injured tissue in the adult central nervous system （CNS） still remains a big challenge for current biomed- ical research and its upcoming clinical translation. The axonal regeneration of the adu...Functional repair of injured tissue in the adult central nervous system （CNS） still remains a big challenge for current biomed- ical research and its upcoming clinical translation. The axonal regeneration of the adult CNS is generally low, and it is addi- tionally restricted after injury by the presence of inhibitory mol- ecules, generated by the glial scar.展开更多
Sutures,as necessary medical devices for postoperative treatment,are no longer merely supportive but are required to have advanced functions to promote repair.Here,we report an absorbable self-powered electrical stimu...Sutures,as necessary medical devices for postoperative treatment,are no longer merely supportive but are required to have advanced functions to promote repair.Here,we report an absorbable self-powered electrical stimulation suture.The suture is composed entirely of absorbable materials(magnesium,polylactic acid,and polycaprolactone)and can be used in vivo for incision closure and repair.The suture has the capacity to generate spontaneous electrical stimulation in response to body movement,allowing for accelerated tissue reconstruction.An in vivo muscle incision repair model demonstrated that the wound healing rate under treatment with this suture was 1.6 times faster than that of commercial sutures,proving its postoperative therapeutic capability.展开更多
Mesenchymal stem cells(MSCs)exhibit significant therapeutic potential in deep tissue repair due to their exceptional paracrine functions and immunomodulatory abilities.However,fabricating microsphere-based hydrogels t...Mesenchymal stem cells(MSCs)exhibit significant therapeutic potential in deep tissue repair due to their exceptional paracrine functions and immunomodulatory abilities.However,fabricating microsphere-based hydrogels that can simultaneously enhance MSC viability and retention in inflammatory wound microenvironments remain challenging.Herein,the MSC-encapsulated microsphere blocks incorporated with MnO_(2)@EGCG/Cu(II)(MEC)nanozymes are designed to relieve excessive oxidative stress and improve stem cell therapy in deep tissue repair.The MEC nanozymes exhibit enhanced biocompatibility,possess multiple enzymatic catalytic activities,and effectively protect MSCs from H2O_(2)-induced oxidative damage.The GSM blocks,composed of methacryloyl gelatin and methacryloyl silk fibroin(GSM)microspheres,are further cross-linked using phenylboronic acid-modified methacryloyl gelatin(GelMA-PBA)and polyvinyl alcohol(PVA)(GP hydrogel)via dynamic covalent and permanent covalent bonds.The results of in vivo experiments reveal that the GP-GSM@MEC hydrogel not only adapts to irregular deep tissue wounds but also enhances the mechanical properties and tissue retention of GSM blocks through in situ photocrosslinking.Furthermore,GSM blocks significantly accelerated inflammatory deep tissue wound healing by alleviating excessive oxidative stress and tissue hypoxia,promoting tissue infiltration and vascularization.Therefore,this work provides an intelligent GSM block design strategy for MSC delivery,showing a promising alternative approach to improve the healing of inflammatory deep tissue defects.展开更多
Engineering biomaterials that actively interface with and instruct their biological milieu have given rise to a new generation of platforms for tissue repair and companion diagnostics.Among them,aerogel scaffolds,with...Engineering biomaterials that actively interface with and instruct their biological milieu have given rise to a new generation of platforms for tissue repair and companion diagnostics.Among them,aerogel scaffolds,with their ultra-porous architecture,ultralow density,tunable mechanics,and versatile chemistries,have emerged as transformative candidates capable of emulating and interpreting extracellular environments.This review highlights up-to-date advances shaping the landscape of aerogel-based scaffolds in tissue repair and diagnostic applications.We first summarize emerging fabrication and assembly strategies,including sol-gel processing,freeze-drying,electrospinning,and 3D printing,which unlock hierarchical morphologies and bioinspired features.The recent implementations of intelligent aerogels for tissue repair and neuroregeneration are then highlighted,together with related applications in bioactive functionalization,immune modulation,wound healing,sustained drug delivery,and moist repair dressings.Meanwhile,we outline aerogel-based disease diagnosis regarding genotypic physiological cues,focusing on faithfully detecting nucleic acids,tumor biopsy,virus antigen testing of infectious disease,and state-of-the-art demos with innovative signal transduction mechanisms.Data-driven strategies powered by machine learning are also reviewed,alongside integration into smart wearables for self-adapting,responsive platforms.Finally,persisting challenges and present perspective of aerogel scaffolds in medicine research and practice are also discussed.展开更多
Regenerative medicine endeavors to restore damaged tissues and organs utilizing biological approaches.Uti-lizing biomaterials to target and regulate the pathophysiological processes of injured tissues stands as a cruc...Regenerative medicine endeavors to restore damaged tissues and organs utilizing biological approaches.Uti-lizing biomaterials to target and regulate the pathophysiological processes of injured tissues stands as a crucial method in propelling this field forward.The Extracellular Vesicles-in-Hydrogel(EViH)system amalgamates the advantages of extracellular vesicles(EVs)and hydrogels,rendering it a prominent biomaterial in regenerative medicine with substantial potential for clinical translation.This review elucidates the development and benefits of the EViH system in tissue regeneration,emphasizing the interaction and impact of EVs and hydrogels.Furthermore,it succinctly outlines the pathophysiological characteristics of various types of tissue injuries such as wounds,bone and cartilage injuries,cardiovascular diseases,nerve injuries,as well as liver and kidney in-juries,underscoring how EViH systems target these processes to address related tissue damage.Lastly,it explores the challenges and prospects in further advancing EViH-based tissue regeneration,aiming to impart a compre-hensive understanding of EViH.The objective is to furnish a thorough overview of EViH in enhancing regen-erative medicine applications and to inspire researchers to devise innovative tissue engineering materials for regenerative medicine.展开更多
The biomimetic materials that replicate the mechanical gradient transitions from muscle to tendon to bone remain a significant challenge in tissue engineering,particularly through simple and environmentally friendly a...The biomimetic materials that replicate the mechanical gradient transitions from muscle to tendon to bone remain a significant challenge in tissue engineering,particularly through simple and environmentally friendly approaches.This mechanical gradient is crucial for applications such as rotator cuff and Achilles tendon repair patches,which prevent stress shielding and ensure uniform stress distribution,addressing the stress concentration issues common in traditional repairs.Here,we present a strategy that achieves high strength even at high water content,enabling programmable modulus/structural gradients with broad applicability.Using rotator cuff tendon repair as a model system,we demonstrate successful in vivo tissue regeneration with integrated real-time sensing capabilities,providing quantitative data for rehabilitation protocols.The hydrogels exhibit precisely controlled regional mechanical properties and seamless interface transitions,mimicking the hierarchical structure of native tissue.This approach not only improves healing outcomes compared to conventional methods but also establishes a quantitative standard for rehabilitation training.展开更多
This comprehensive review elucidates the critical role of efferocytosis in tissue repair and regeneration processes,while systematically exploring innovative approaches through which tissue engineering strategies can ...This comprehensive review elucidates the critical role of efferocytosis in tissue repair and regeneration processes,while systematically exploring innovative approaches through which tissue engineering strategies can modulate efferocytosis to optimize these biological processes.The manuscript is structured to first establish a fundamental understanding of efferocytosis,encompassing its core concepts,molecular mechanisms,and physiological functions within tissue repair.Subsequently,it provides an in-depth analysis of the regulatory role of effer-ocytosis in inflammatory response modulation during tissue repair cascades.The review culminates in a detailed investigation of cutting-edge tissue engineering applications specifically designed to manipulate efferocytosis pathways.Substantial evidence from recent studies has unequivocally demonstrated that efferocytosis serves as a crucial biological process in maintaining tissue homeostasis and orchestrating injury repair mechanisms.In this context,tissue engineering has emerged as a transformative approach,offering precise control over efferocytosis enhancement,inflammation resolution,and tissue regeneration processes.Through sophisticated integration of bioactive factor regulation,advanced scaffolding materials,and targeted cellular interactions,tissue engineering platforms have established novel therapeutic paradigms,providing unprecedented insights and innovative strategies for the treatment of diverse pathological conditions.展开更多
Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted t...Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.展开更多
The authors regret to inform that fluorescein sodium labelling of CeCyan+L(right image)under slit lamp observation was mistakenly taken.This correction does not change any description,results or con-clusions of the or...The authors regret to inform that fluorescein sodium labelling of CeCyan+L(right image)under slit lamp observation was mistakenly taken.This correction does not change any description,results or con-clusions of the original paper.The authors apologize for any confusion this may have caused.The corrected versions are shown below.展开更多
Regulator of G protein signaling 12(RGS12)belongs to the superfamily of RGS pro-teins defined by a conserved RGS domain that canonically binds and deactivates heterotrimeric G-proteins.As the largest family member,RGS...Regulator of G protein signaling 12(RGS12)belongs to the superfamily of RGS pro-teins defined by a conserved RGS domain that canonically binds and deactivates heterotrimeric G-proteins.As the largest family member,RGS12 is widely expressed in many cells and tissues.In the past few decades,it has been found that RGS12 affects the activity of various cells in the human body,participates in many physiological and pathological processes,and plays an important role in the pathogenesis of many diseases.Here,we set out to comprehensively re-view the role of RGS12 in human diseases and its mechanisms,highlighting the possibility of RGS12 as a therapeutic target for the treatment of human diseases.展开更多
Biomedical patches have demonstrated value in promoting soft tissue repair or anti-adhesion.Research tendency in this area focuses on developing more controllable patches to meet the complex clinical scenarios.Herein,...Biomedical patches have demonstrated value in promoting soft tissue repair or anti-adhesion.Research tendency in this area focuses on developing more controllable patches to meet the complex clinical scenarios.Herein,inspired by the controllable adhesion of suction cups and the antifouling properties of eyeball surfaces,we propose an anisotropic patch with‘revocable’adhesion mechanisms.For the adhesive-side,the initial adhesion forces mainly rely on suction cup’s physical interactions to allow adequate position adjustment,followed by the reaction of N-hydroxysuccinimide ester group with the tissue for firm covalent bonding.This multi-adhesive mechanism enables the spatiotemporal control of adhesive behavior.In contrast,on the barrier-side,the highly hydrated surface derived from polyethylene glycol and polyvinyl alcohol hydrogels displays no affinity for tissue proteins,thus effectively preventing tissue adhesion.Moreover,the intrinsic pores and charges enable the adsorption of positively charged inflammatory factors,while the loaded drugs can release sustainably.In vivo experiments demonstrate the patch’s strong yet controllable adhesion,effective in reducing inflammation and promoting healing.This innovative design introduces a new paradigm of‘revocable’adhesion,offering significant clinical potential for soft tissue repair and adhesion prevention.展开更多
Three-dimensional(3D)stem cell culture systems have attracted considerable attention as a way to better mimic the complex interactions between individual cells and the extracellular matrix(ECM)that occur in vivo.Moreo...Three-dimensional(3D)stem cell culture systems have attracted considerable attention as a way to better mimic the complex interactions between individual cells and the extracellular matrix(ECM)that occur in vivo.Moreover,3D cell culture systems have unique properties that help guide specific functions,growth,and processes of stem cells(e.g.,embryogenesis,morphogenesis,and organogenesis).Thus,3D stem cell culture systems that mimic in vivo environments enable basic research about various tissues and organs.In this review,we focus on the advanced therapeutic applications of stem cell-based 3D culture systems generated using different engineering techniques.Specifically,we summarize the historical advancements of 3D cell culture systems and discuss the therapeutic applications of stem cell-based spheroids and organoids,including engineering techniques for tissue repair and regeneration.展开更多
As a type of elastomeric polymers,non-degradable polyurethanes(PUs)have a long history of being used in clinics,whereas biodegradable PUs have been developed in recent decades,primarily for tissue repair and regenerat...As a type of elastomeric polymers,non-degradable polyurethanes(PUs)have a long history of being used in clinics,whereas biodegradable PUs have been developed in recent decades,primarily for tissue repair and regeneration.Biodegradable thermoplastic(linear)PUs are soft and elastic polymeric biomaterials with high mechanical strength,which mimics the mechanical properties of soft and elastic tissues.Therefore,biodegradable thermoplastic polyurethanes are promising scaffolding materials for soft and elastic tissue repair and regeneration.Generally,PUs are synthesized by linking three types of changeable blocks:diisocyanates,diols,and chain extenders.Alternating the combination of these three blocks can finely tailor the physio-chemical properties and generate new functional PUs.These PUs have excellent processing flexibilities and can be fabricated into three-dimensional(3D)constructs using conventional and/or advanced technologies,which is a great advantage compared with cross-linked thermoset elastomers.Additionally,they can be combined with biomolecules to incorporate desired bioactivities to broaden their biomedical applications.In this review,we comprehensively summarized the synthesis,structures,and properties of biodegradable thermoplastic PUs,and introduced their multiple applications in tissue repair and regeneration.A whole picture of their design and applications along with discussions and perspectives of future directions would provide theoretical and technical supports to inspire new PU development and novel applications.展开更多
Inflammatory bowel disease(IBD)is a chronic,non-specific,recurrent inflammatory disease,majorly affecting the gastrointestinal tract.Due to its unclear pathogenesis,the current therapeutic strategy for IBD is focused ...Inflammatory bowel disease(IBD)is a chronic,non-specific,recurrent inflammatory disease,majorly affecting the gastrointestinal tract.Due to its unclear pathogenesis,the current therapeutic strategy for IBD is focused on symptoms alleviation.Autophagy is a lysosome-mediated catabolic process for maintaining cellular homeostasis.Genome-wide association studies and subsequent functional studies have highlighted the critical role of autophagy in IBD via a number of mechanisms,including modulating macrophage function.Macrophages are the gatekeepers of intestinal immune homeostasis,especially involved in regulating inflammation remission and tissue repair.Interestingly,many autophagic proteins and IBD-related genes have been revealed to regulate macrophage function,suggesting that macrophage autophagy is a potentially important process implicated in IBD regulation.Here,we have summarized current understanding of macrophage autophagy function in pathogen and apoptotic cell clearance,inflammation remission and tissue repair regulation in IBD,and discuss how this knowledge can be used as a strategy for IBD treatment.展开更多
Wound healing,tissue repair and regenerative medicine are in great demand,and great achievements in these fields have been made.The traditional strategy of tissue repair and regeneration has focused on the level of ti...Wound healing,tissue repair and regenerative medicine are in great demand,and great achievements in these fields have been made.The traditional strategy of tissue repair and regeneration has focused on the level of tissues and organs directly;however,the basic process of repair at the cell level is often neglected.Because the cell is the basic unit of organism structure and function;cell damage is caused first by ischemia or ischemia-reperfusion after severe trauma and injury.Then,damage to tissues and organs occurs with massive cell damage,apoptosis and even cell death.Thus,how to achieve the aim of perfect repair and regeneration?The basic process of tissue or organ repair and regeneration should involve repair of cells first,then tissues and organs.In this manuscript,it is my consideration about how to repair the cell first,then regenerate the tissues and organs.展开更多
文摘Mesenchymal stem cells （MSCs） have great potential for treating various diseases, especially those related to tissue damage involving immune reactions. Various studies have demonstrated that MSCs are strongly immunosuppressive in vitro and in vivo. Our recent studies have shown that un-stimulated MSCs are indeed incapable of immunosuppression; they become potently immunosuppressive upon stimulation with the supernatant of activated lymphocytes, or with combinations of IFN-γ, with TNF-α, IL-1α or IL-1β. This observation revealed that under certain circumstances, inflammatory cytokines can actually become immunosuppressive. We showed that there is a species variation in the mechanisms of MSC-mediated immunosuppression： immunosuppression by cytokine-primed mouse MSCs is mediated by nitric oxide （NO）, whereas immunosuppression by cytokine-primed human MSCs is executed through indoleamine 2, 3-dioxygenase （IDO）. Additionally, upon stimulation with the inflammatory cytokines, both mouse and human MSCs secrete several leukocyte chemokines that apparently serve to attract immune cells into the proximity with MSCs, where NO or IDO is predicted to be most active. Therefore, immunosuppression by inflammatory cytokine-stimulated MSCs occurs via the concerted action of chemokines and immune-inhibitory NO or IDO produced by MSCs. Thus, our results provide novel information about the mechanisms of MSC-mediated immunosuppression and for better application of MSCs in treating tissue injuries induced by immune responses.
基金This research was funded by Jiangsu Province’s Key Project of Science and Technology(Grant No.BE2018644)Changzhou Health Commission’s Young Talents Science and Technology project(Grant No.QN202029).
文摘Bone tissue engineering(BTE)has proven to be a promising strategy for bone defect repair.Due to its excellent biological properties,gelatin methacrylate(GelMA)hydrogels have been used as bioinks for 3D bioprinting in some BTE studies to produce scaffolds for bone regeneration.However,applications for load-bearing defects are limited by poor mechanical properties and a lack of bioactivity.In this study,3D printing technology was used to create nano-attapulgite(nano-ATP)/GelMA composite hydrogels loaded into mouse bone mesenchymal stem cells(BMSCs)and mouse umbilical vein endothelial cells(MUVECs).The bioprintability,physicochemical properties,and mechanical properties were all thoroughly evaluated.Our findings showed that nano-ATP groups outperform the control group in terms of printability,indicating that nano-ATP is beneficial for printability.Additionally,after incorporation with nano-ATP,the mechanical strength of the composite hydrogels was significantly improved,resulting in adequate mechanical properties for bone regeneration.The presence of nano-ATP in the scaffolds has also been stud-ied for cell-material interactions.The findings show that cells within the scaffold not only have high viability but also a clear proclivity to promote osteogenic differentiation of BMSCs.Besides,the MUVECs-loaded composite hydrogels demonstrated increased angiogenic activity.A cranial defect model was also developed to evaluate the bone repair capability of scaffolds loaded with rat BMSCs.According to histo-logical analysis,cell-laden nano-ATP composite hydrogels can effectively im prove bone regeneration and promote angiogenesis.This study demonstrated the potential of nano-ATP for bone tissue engineering,which should also increase the clinical practicality of nano-ATP.
文摘Schwann cells are glial cells of peripheral nervous system, responsible for axonal myelination and ensheathing, as well as tissue repair following a peripheral nervous system injury. They are one of several cell types that are widely studied and most commonly used for cell transplantation to treat spinal cord injury, due to their intrinsic characteristics including the ability to secrete a variety of neurotrophic factors. This mini review summarizes the recent findings of endogenous Schwann cells after spinal cord injury and discusses their role in tissue repair and axonal regeneration. After spinal cord injury, numerous endogenous Schwann cells migrate into the lesion site from the nerve roots, involving in the construction of newly formed repaired tissue and axonal myelination. These invading Schwann cells also can move a long distance away from the injury site both rostrally and caudally. In addition, Schwann cells can be induced to migrate by minimal insults （such as scar ablation） within the spinal cord and integrate with astrocytes under certain circumstances. More importantly, the host Schwann cells can be induced to migrate into spinal cord by transplantation of different cell types, such as exogenous Schwann cells, olfactory ensheathing cells, and bone marrow-derived stromal stem cells. Migration of endogenous Schwann cells following spinal cord injury is a common natural phenomenon found both in animal and human, and the myelination by Schwann cells has been examined effective in signal conduction electrophysiologically. Therefore, if the inherent properties of endogenous Schwann cells could be developed and utilized, it would offer a new avenue for the restoration of injured spinal cord.
文摘Neurological disorders are diseases of the central and peripheral nervous systems.These disorders include Alzheimer＇s disease,epilepsy,brain tumor,and cerebrovascular diseases（stroke,migraine and other headache disorders,multiple sclerosis,Parkinson＇s disease,and neuroinfections）.
文摘BACKGROUND Laparoscopic sacrocolpopexy for pelvic organ prolapse(POP)is a new and widely used approach;however,ever since the United States Food and Drug Administration warned against the use of surgical mesh,repairs performed using patients’tissues[i.e.native tissue repair(NTR)]instead of mesh have attracted much attention.At our hospital,laparoscopic sacrocolpopexy(the Shull method)was introduced in 2017.However,patients with more severe POP who have a long vaginal canal and overextended uterosacral ligaments may not be candidates for this procedure.AIM To validate a new NTR treatment for POP,we examined patients undergoing laparoscopic vaginal stump–round ligament fixation(the Kakinuma method).METHODS The study patients were 30 individuals with POP who underwent surgery using the Kakinuma method between January 2020 and December 2021 and who were followed up for>12 mo after surgery.We retrospectively examined surgical outcomes for surgery duration,blood loss,intraoperative complications,and incidence of recurrence.The Kakinuma method involves round ligament suturing and fixation on both sides,effectively lifting the vaginal stump after laparoscopic hysterectomy.RESULTS The patients’mean age was 66.5±9.1(45-82)years,gravidity was 3.1±1.4(2-7),parity was 2.5±0.6(2-4)times,and body mass index was 24.5±3.3(20.9-32.8)kg/m2.According to the POP quantification stage classification,there were 8 patients with stage Ⅱ,11 with stage Ⅲ,and 11 with stage Ⅳ.The mean surgery duration was 113.4±22.6(88-148)min,and the mean blood loss was 26.5±39.7(10-150)mL.There were no perioperative complications.None of the patients exhibited reduced activities of daily living or cognitive impairment after hospital discharge.No cases of POP recurrence were observed 12 mo after the operation.CONCLUSION The Kakinuma method,similar to conventional NTR,may be an effective treatment for POP.
基金supported by MEYS of the Czech Republic,No.LO1309
文摘Functional repair of injured tissue in the adult central nervous system （CNS） still remains a big challenge for current biomed- ical research and its upcoming clinical translation. The axonal regeneration of the adult CNS is generally low, and it is addi- tionally restricted after injury by the presence of inhibitory mol- ecules, generated by the glial scar.
基金financially supported by the National Natural Science Foundation of China(82301331)。
文摘Sutures,as necessary medical devices for postoperative treatment,are no longer merely supportive but are required to have advanced functions to promote repair.Here,we report an absorbable self-powered electrical stimulation suture.The suture is composed entirely of absorbable materials(magnesium,polylactic acid,and polycaprolactone)and can be used in vivo for incision closure and repair.The suture has the capacity to generate spontaneous electrical stimulation in response to body movement,allowing for accelerated tissue reconstruction.An in vivo muscle incision repair model demonstrated that the wound healing rate under treatment with this suture was 1.6 times faster than that of commercial sutures,proving its postoperative therapeutic capability.
基金the Science and Technology Program of Suzhou(No.SYG202343)Research Fund(No.GP202410)from Advanced Ocean Institute of Southeast University,Nantong.
文摘Mesenchymal stem cells(MSCs)exhibit significant therapeutic potential in deep tissue repair due to their exceptional paracrine functions and immunomodulatory abilities.However,fabricating microsphere-based hydrogels that can simultaneously enhance MSC viability and retention in inflammatory wound microenvironments remain challenging.Herein,the MSC-encapsulated microsphere blocks incorporated with MnO_(2)@EGCG/Cu(II)(MEC)nanozymes are designed to relieve excessive oxidative stress and improve stem cell therapy in deep tissue repair.The MEC nanozymes exhibit enhanced biocompatibility,possess multiple enzymatic catalytic activities,and effectively protect MSCs from H2O_(2)-induced oxidative damage.The GSM blocks,composed of methacryloyl gelatin and methacryloyl silk fibroin(GSM)microspheres,are further cross-linked using phenylboronic acid-modified methacryloyl gelatin(GelMA-PBA)and polyvinyl alcohol(PVA)(GP hydrogel)via dynamic covalent and permanent covalent bonds.The results of in vivo experiments reveal that the GP-GSM@MEC hydrogel not only adapts to irregular deep tissue wounds but also enhances the mechanical properties and tissue retention of GSM blocks through in situ photocrosslinking.Furthermore,GSM blocks significantly accelerated inflammatory deep tissue wound healing by alleviating excessive oxidative stress and tissue hypoxia,promoting tissue infiltration and vascularization.Therefore,this work provides an intelligent GSM block design strategy for MSC delivery,showing a promising alternative approach to improve the healing of inflammatory deep tissue defects.
基金supported by National Natural Science Foundation of China(22577094,22307098,and 12375334)Key Projects of Wenzhou Science and Technology Bureau(ZN2024009)+1 种基金the Key program of WIUCASQD2021012 from Wenzhou Institute,University of Chinese Academy of SciencesJoint Research Centre on Medicine,Wenzhou Institute,University of Chinese Academy of Sciences Xiangshan Hospital of Wenzhou Medical University(XSZD2024006).
文摘Engineering biomaterials that actively interface with and instruct their biological milieu have given rise to a new generation of platforms for tissue repair and companion diagnostics.Among them,aerogel scaffolds,with their ultra-porous architecture,ultralow density,tunable mechanics,and versatile chemistries,have emerged as transformative candidates capable of emulating and interpreting extracellular environments.This review highlights up-to-date advances shaping the landscape of aerogel-based scaffolds in tissue repair and diagnostic applications.We first summarize emerging fabrication and assembly strategies,including sol-gel processing,freeze-drying,electrospinning,and 3D printing,which unlock hierarchical morphologies and bioinspired features.The recent implementations of intelligent aerogels for tissue repair and neuroregeneration are then highlighted,together with related applications in bioactive functionalization,immune modulation,wound healing,sustained drug delivery,and moist repair dressings.Meanwhile,we outline aerogel-based disease diagnosis regarding genotypic physiological cues,focusing on faithfully detecting nucleic acids,tumor biopsy,virus antigen testing of infectious disease,and state-of-the-art demos with innovative signal transduction mechanisms.Data-driven strategies powered by machine learning are also reviewed,alongside integration into smart wearables for self-adapting,responsive platforms.Finally,persisting challenges and present perspective of aerogel scaffolds in medicine research and practice are also discussed.
基金supported by the National Nature Science Foundation of China(No.52103170,and No.82470978)Natural Science Foundation of Shandong Province(ZR2020MH183)Qingdao Marine Science and Technology Center Shandong Province Special Fund“Frontier Technology Free Exploration”(No.12-04).
文摘Regenerative medicine endeavors to restore damaged tissues and organs utilizing biological approaches.Uti-lizing biomaterials to target and regulate the pathophysiological processes of injured tissues stands as a crucial method in propelling this field forward.The Extracellular Vesicles-in-Hydrogel(EViH)system amalgamates the advantages of extracellular vesicles(EVs)and hydrogels,rendering it a prominent biomaterial in regenerative medicine with substantial potential for clinical translation.This review elucidates the development and benefits of the EViH system in tissue regeneration,emphasizing the interaction and impact of EVs and hydrogels.Furthermore,it succinctly outlines the pathophysiological characteristics of various types of tissue injuries such as wounds,bone and cartilage injuries,cardiovascular diseases,nerve injuries,as well as liver and kidney in-juries,underscoring how EViH systems target these processes to address related tissue damage.Lastly,it explores the challenges and prospects in further advancing EViH-based tissue regeneration,aiming to impart a compre-hensive understanding of EViH.The objective is to furnish a thorough overview of EViH in enhancing regen-erative medicine applications and to inspire researchers to devise innovative tissue engineering materials for regenerative medicine.
基金supported by the Fundamental Research Funds for the Central Universities(No.2022JC013)National NaturalScience Foundation of China(Grant No.12204271)+1 种基金Natural Science Foundation of Shandong Province of China(No.ZR2021MH023)National Natural Science Foundation of China(No.62401343).
文摘The biomimetic materials that replicate the mechanical gradient transitions from muscle to tendon to bone remain a significant challenge in tissue engineering,particularly through simple and environmentally friendly approaches.This mechanical gradient is crucial for applications such as rotator cuff and Achilles tendon repair patches,which prevent stress shielding and ensure uniform stress distribution,addressing the stress concentration issues common in traditional repairs.Here,we present a strategy that achieves high strength even at high water content,enabling programmable modulus/structural gradients with broad applicability.Using rotator cuff tendon repair as a model system,we demonstrate successful in vivo tissue regeneration with integrated real-time sensing capabilities,providing quantitative data for rehabilitation protocols.The hydrogels exhibit precisely controlled regional mechanical properties and seamless interface transitions,mimicking the hierarchical structure of native tissue.This approach not only improves healing outcomes compared to conventional methods but also establishes a quantitative standard for rehabilitation training.
基金support from the Sichuan Sci-ence and Technology Program(2024NSFSC0002)the National Natural Science Foundation of China(Grant No.824B2073)+1 种基金the Frontiers Medical Center,Tianfu Jincheng Laboratory Foundation(TFJC2023010002)the“1.3.5”Project for Disciplines of Excellence,West China Hospital,Sichuan University(ZYGD23037).
文摘This comprehensive review elucidates the critical role of efferocytosis in tissue repair and regeneration processes,while systematically exploring innovative approaches through which tissue engineering strategies can modulate efferocytosis to optimize these biological processes.The manuscript is structured to first establish a fundamental understanding of efferocytosis,encompassing its core concepts,molecular mechanisms,and physiological functions within tissue repair.Subsequently,it provides an in-depth analysis of the regulatory role of effer-ocytosis in inflammatory response modulation during tissue repair cascades.The review culminates in a detailed investigation of cutting-edge tissue engineering applications specifically designed to manipulate efferocytosis pathways.Substantial evidence from recent studies has unequivocally demonstrated that efferocytosis serves as a crucial biological process in maintaining tissue homeostasis and orchestrating injury repair mechanisms.In this context,tissue engineering has emerged as a transformative approach,offering precise control over efferocytosis enhancement,inflammation resolution,and tissue regeneration processes.Through sophisticated integration of bioactive factor regulation,advanced scaffolding materials,and targeted cellular interactions,tissue engineering platforms have established novel therapeutic paradigms,providing unprecedented insights and innovative strategies for the treatment of diverse pathological conditions.
基金supported by the National Natural Science Foundation of China,Nos.32271389,31900987(both to PY)the Natural Science Foundation of Jiangsu Province,No.BK20230608(to JJ)。
文摘Regulatory T cells,a subset of CD4^(+)T cells,play a critical role in maintaining immune tolerance and tissue homeostasis due to their potent immunosuppressive properties.Recent advances in research have highlighted the important therapeutic potential of Tregs in neurological diseases and tissue repair,emphasizing their multifaceted roles in immune regulation.This review aims to summarize and analyze the mechanisms of action and therapeutic potential of Tregs in relation to neurological diseases and neural regeneration.Beyond their classical immune-regulatory functions,emerging evidence points to non-immune mechanisms of regulatory T cells,particularly their interactions with stem cells and other non-immune cells.These interactions contribute to optimizing the repair microenvironment and promoting tissue repair and nerve regeneration,positioning non-immune pathways as a promising direction for future research.By modulating immune and non-immune cells,including neurons and glia within neural tissues,Tregs have demonstrated remarkable efficacy in enhancing regeneration in the central and peripheral nervous systems.Preclinical studies have revealed that Treg cells interact with neurons,glial cells,and other neural components to mitigate inflammatory damage and support functional recovery.Current mechanistic studies show that Tregs can significantly promote neural repair and functional recovery by regulating inflammatory responses and the local immune microenvironment.However,research on the mechanistic roles of regulatory T cells in other diseases remains limited,highlighting substantial gaps and opportunities for exploration in this field.Laboratory and clinical studies have further advanced the application of regulatory T cells.Technical advances have enabled efficient isolation,ex vivo expansion and functionalization,and adoptive transfer of regulatory T cells,with efficacy validated in animal models.Innovative strategies,including gene editing,cell-free technologies,biomaterial-based recruitment,and in situ delivery have expanded the therapeutic potential of regulatory T cells.Gene editing enables precise functional optimization,while biomaterial and in situ delivery technologies enhance their accumulation and efficacy at target sites.These advancements not only improve the immune-regulatory capacity of regulatory T cells but also significantly enhance their role in tissue repair.By leveraging the pivotal and diverse functions of Tregs in immune modulation and tissue repair,regulatory T cells–based therapies may lead to transformative breakthroughs in the treatment of neurological diseases.
文摘The authors regret to inform that fluorescein sodium labelling of CeCyan+L(right image)under slit lamp observation was mistakenly taken.This correction does not change any description,results or con-clusions of the original paper.The authors apologize for any confusion this may have caused.The corrected versions are shown below.
基金supported by the National Natural Science Foundation of China(No.82100889)China Postdoctoral Science Foundation(No.2024M753868)+1 种基金Chongqing Doctor“Through Train”Project(No.CSTB2022BSXM-JCX0022)Chongqing Shapingba District 2024 Techmology lnnovation Project(No.2024114).
文摘Regulator of G protein signaling 12(RGS12)belongs to the superfamily of RGS pro-teins defined by a conserved RGS domain that canonically binds and deactivates heterotrimeric G-proteins.As the largest family member,RGS12 is widely expressed in many cells and tissues.In the past few decades,it has been found that RGS12 affects the activity of various cells in the human body,participates in many physiological and pathological processes,and plays an important role in the pathogenesis of many diseases.Here,we set out to comprehensively re-view the role of RGS12 in human diseases and its mechanisms,highlighting the possibility of RGS12 as a therapeutic target for the treatment of human diseases.
基金The National Natural Science Foundation of China(52403189)the Natural Science Foundation of Jiangsu Province(BK20220170)+1 种基金Shenzhen Second People’s Hospital Clinical Research Fund of Shenzhen High-level Hospital Construction Project(Grant No.20243357016)the Wenzhou Institute UCAS startup fund(WIUCASQD2024009).
文摘Biomedical patches have demonstrated value in promoting soft tissue repair or anti-adhesion.Research tendency in this area focuses on developing more controllable patches to meet the complex clinical scenarios.Herein,inspired by the controllable adhesion of suction cups and the antifouling properties of eyeball surfaces,we propose an anisotropic patch with‘revocable’adhesion mechanisms.For the adhesive-side,the initial adhesion forces mainly rely on suction cup’s physical interactions to allow adequate position adjustment,followed by the reaction of N-hydroxysuccinimide ester group with the tissue for firm covalent bonding.This multi-adhesive mechanism enables the spatiotemporal control of adhesive behavior.In contrast,on the barrier-side,the highly hydrated surface derived from polyethylene glycol and polyvinyl alcohol hydrogels displays no affinity for tissue proteins,thus effectively preventing tissue adhesion.Moreover,the intrinsic pores and charges enable the adsorption of positively charged inflammatory factors,while the loaded drugs can release sustainably.In vivo experiments demonstrate the patch’s strong yet controllable adhesion,effective in reducing inflammation and promoting healing.This innovative design introduces a new paradigm of‘revocable’adhesion,offering significant clinical potential for soft tissue repair and adhesion prevention.
基金supported by the National Research Foundation of Korea(NRF)grants funded by the Korean government(NRF-2021R1A4A3025206,NRF-2019M3A9H1103737,NRF-2021M3E5E7026407,NRF-2019R1I1A3A0106345).
文摘Three-dimensional(3D)stem cell culture systems have attracted considerable attention as a way to better mimic the complex interactions between individual cells and the extracellular matrix(ECM)that occur in vivo.Moreover,3D cell culture systems have unique properties that help guide specific functions,growth,and processes of stem cells(e.g.,embryogenesis,morphogenesis,and organogenesis).Thus,3D stem cell culture systems that mimic in vivo environments enable basic research about various tissues and organs.In this review,we focus on the advanced therapeutic applications of stem cell-based 3D culture systems generated using different engineering techniques.Specifically,we summarize the historical advancements of 3D cell culture systems and discuss the therapeutic applications of stem cell-based spheroids and organoids,including engineering techniques for tissue repair and regeneration.
基金acknowledge the partial financial support from the American Heart Association(Beginning Grant-in-Aid,14BGIA20510066,Y.H.)the National Science Foundation(Faculty Career Development(CAREER)award,#1554835 Y.H.)the National Institutes of Health(R01HD097330,R21HD090680 and R15HL140503,Y.H.)in the United States of America.
文摘As a type of elastomeric polymers,non-degradable polyurethanes(PUs)have a long history of being used in clinics,whereas biodegradable PUs have been developed in recent decades,primarily for tissue repair and regeneration.Biodegradable thermoplastic(linear)PUs are soft and elastic polymeric biomaterials with high mechanical strength,which mimics the mechanical properties of soft and elastic tissues.Therefore,biodegradable thermoplastic polyurethanes are promising scaffolding materials for soft and elastic tissue repair and regeneration.Generally,PUs are synthesized by linking three types of changeable blocks:diisocyanates,diols,and chain extenders.Alternating the combination of these three blocks can finely tailor the physio-chemical properties and generate new functional PUs.These PUs have excellent processing flexibilities and can be fabricated into three-dimensional(3D)constructs using conventional and/or advanced technologies,which is a great advantage compared with cross-linked thermoset elastomers.Additionally,they can be combined with biomolecules to incorporate desired bioactivities to broaden their biomedical applications.In this review,we comprehensively summarized the synthesis,structures,and properties of biodegradable thermoplastic PUs,and introduced their multiple applications in tissue repair and regeneration.A whole picture of their design and applications along with discussions and perspectives of future directions would provide theoretical and technical supports to inspire new PU development and novel applications.
基金supported by the Shenzhen Fundamental Research Program(No.SGDX20210823103804030)Science and Technology Development Fund,Macao SAR(No.0025/2022/A1)+3 种基金the 2020 Guangdong Provincial Science and Technology Innovation Strategy Special Fund(Guangdong-Hong Kong-Macao Joint Lab)(No.2020B1212030006)Guangdong Basic and Applied Basic Research Foundation(No.2022A1515012416)National Natural Science Foundation of China(No.31871024)the University of Macao grants(No.MYRG2019-00129-ICMS)awarded to JHL.
文摘Inflammatory bowel disease(IBD)is a chronic,non-specific,recurrent inflammatory disease,majorly affecting the gastrointestinal tract.Due to its unclear pathogenesis,the current therapeutic strategy for IBD is focused on symptoms alleviation.Autophagy is a lysosome-mediated catabolic process for maintaining cellular homeostasis.Genome-wide association studies and subsequent functional studies have highlighted the critical role of autophagy in IBD via a number of mechanisms,including modulating macrophage function.Macrophages are the gatekeepers of intestinal immune homeostasis,especially involved in regulating inflammation remission and tissue repair.Interestingly,many autophagic proteins and IBD-related genes have been revealed to regulate macrophage function,suggesting that macrophage autophagy is a potentially important process implicated in IBD regulation.Here,we have summarized current understanding of macrophage autophagy function in pathogen and apoptotic cell clearance,inflammation remission and tissue repair regulation in IBD,and discuss how this knowledge can be used as a strategy for IBD treatment.
文摘Wound healing,tissue repair and regenerative medicine are in great demand,and great achievements in these fields have been made.The traditional strategy of tissue repair and regeneration has focused on the level of tissues and organs directly;however,the basic process of repair at the cell level is often neglected.Because the cell is the basic unit of organism structure and function;cell damage is caused first by ischemia or ischemia-reperfusion after severe trauma and injury.Then,damage to tissues and organs occurs with massive cell damage,apoptosis and even cell death.Thus,how to achieve the aim of perfect repair and regeneration?The basic process of tissue or organ repair and regeneration should involve repair of cells first,then tissues and organs.In this manuscript,it is my consideration about how to repair the cell first,then regenerate the tissues and organs.
