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
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
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
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
In the vanguard of biomedical innovation,regenerative medicine emerges as a transformative paradigm,concentrating its efforts on rectifying tissue deficits and functional aberrations in patients through the strategic ...In the vanguard of biomedical innovation,regenerative medicine emerges as a transformative paradigm,concentrating its efforts on rectifying tissue deficits and functional aberrations in patients through the strategic augmentation of endogenous cellular processes.Central to this approach is nucleic acid therapy,which offers a novel pathway for tissue regeneration by modulating key signaling pathways.As one of the most effective ways to regulate cell function,nucleic acids are crucial for various tissue regeneration;however,their in vivo therapeutic applications face substantial challenges,including nuclease degradation,cell membrane impermeability,and targeted intracellular transport.Biomaterial-based gene delivery systems offer a solution for stable and localized drug delivery by enabling the controlled overexpression of therapeutic nucleic acids,producing functional regulatory agents.This review presents examples of nucleic acid applications in regenerative medicine,highlighting the synergy between nucleic acids and biomaterial technologies.It underlines the importance of nucleic acid delivery techniques,the choice of therapeutic nucleic acids,and biomaterials for advancing tissue repair.The latest developments in designing nucleic acid biomaterial-based delivery vehicles are explored,the mechanism of nucleic acids in tissue regeneration is elucidated,and their limitations are discussed while considering future directions for the clinical translation of nucleic acid-based therapeutics.展开更多
Mineralization has found widespread use in the fabrication of composite biomaterials for hard tissue regeneration.The current mineralization processes are mainly carried out in neutral aqueous solutions of biomineral ...Mineralization has found widespread use in the fabrication of composite biomaterials for hard tissue regeneration.The current mineralization processes are mainly carried out in neutral aqueous solutions of biomineral counter-ions(a pair of cation and anion that form the corresponding minerals at certain conditions),which are stable only at very low concentrations.This typically results in inefficient mineralization and weak control over biomineral formation.Here,we find that,in the organic solvent glycerol,a variety of biomineral counter-ions(e.g.,Ca/PO_(4),Ca/CO_(3),Ca/SO_(4),Mg/PO_(4),or Fe/OH)corresponding to distinct biominerals at significantly high concentrations(up to hundreds-fold greater than those of simulated body fluid(SBF))are able to form translucent and stable solutions(mineralizing solution of highly concentrated counter-ions(MSCIs)),and mineralization can be triggered upon them with external solvents(e.g.,water or ethanol).Furthermore,with pristine bacterial cellulose(BC)membrane as a model,we demonstrate an effective and controllable mineralization performance of MSCIs on organic substrates.This approach not only forms the homogeneous biominerals on the BC fibers and in the interspaces,but also provides regulations over mineralization rate,mineral content,phase,and dopants.The resulting mineralized BC membranes(MBCs)exhibit high cytocompatibility and favor the proliferation of rat bone marrow mesenchymal stem cells(rBMSC).Following this,we prepare a mineralized bone suture(MBS)from MBC for non-weight bearing bone fixation,which then is tested on a rabbit median sternotomy model.It shows firm fixation of the rabbit sternum without causing discernible toxicity or inflammatory response.This study,by extending the mineralization to the organic solution system of highly concentrated counter-ions,develops a promising strategy to design and build targeted mineral-based composites.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
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
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
Introduction: The cicatricial acceleration method (MAC®) promotes photobiological effects of an anti-inflammatory and healing nature. Its therapeutic radiation is emitted, producing photobiostimulant effects that...Introduction: The cicatricial acceleration method (MAC®) promotes photobiological effects of an anti-inflammatory and healing nature. Its therapeutic radiation is emitted, producing photobiostimulant effects that result in rapid tissue repair and better tissue quality. The treatment of burns has always been a challenge, which involves both performing surgery and controlling and guiding scar regeneration, avoiding possible morbidities. Objective: To evaluate the effects of applying the MAC methodology with an AlGa (aluminum, gallium arsenide) laser on the time and quality of tissue repair in the skin of rats after induced chemical burns. Method: 22 adult male rats were subjected to a second-degree chemical burn on the back using 50% trichloroacetic acid. After the burns, the animals were randomly separated into 2 groups: control and experimental. The control group (G1) received placebo laser therapy and the laser group (G2) underwent laser irradiation with an energy density of 100 J/cm2. Histological analysis and macroscopic evaluation were carried out by means of the paper template method. Results: Group G1 showed (53%) of the necrosis area and group G2 showed (11%) necrosis area. Conclusion: The cicatricial acceleration method (MAC®) favored the repair of wounds caused by a 2nd-degree chemical burn, optimizing time and improving quality.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
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
Adult stem cells are responsible for homeostasis and repair of many tissues.Endogenous adult stem cells reside in certain regions of organs,known as the stem cell niche,which is recognized to have an important role in...Adult stem cells are responsible for homeostasis and repair of many tissues.Endogenous adult stem cells reside in certain regions of organs,known as the stem cell niche,which is recognized to have an important role in regulating tissue maintenance and repair.In wound healing and tissue repair,stem cells are mobilized and recruited to the site of wound,and participate in the repair process.Many regulatory factors are involved in the stem cell-based repair process,including stem cell niches and endogenous wound electric fields,which are present at wound tissues and proved to be important in guiding wound healing.Here we briefly review the role of stem cell niches and endogenous electric fields in tissue repair,and hypothesize that endogenous electric fields become part of stem cell niche in the wound site.展开更多
There has been an increase in the incidence of hypopharyngeal and cervical esophageal cancer worldwide,and hence growing needs for hypopharyngeal and cervical esophageal tissue repair.This work produced a bi-layer com...There has been an increase in the incidence of hypopharyngeal and cervical esophageal cancer worldwide,and hence growing needs for hypopharyngeal and cervical esophageal tissue repair.This work produced a bi-layer composite scaffold with decellularized small intestine submucosa and polylactic-co-glycolic acid,which resembled the layered architectures of its intended tissues.The decellularized small intestine submucosa contained minimal residual DNA(52.5±61.2 ng/mg)and the composite scaffold exhibited satisfactory mechanical properties(a tensile modulus of 21.1±64.8 MPa,an ultimate tensile strength of 14.0±62.9MPa and a failure strain of 26.9±65.1%).The interactions between cells and the respective layers of the scaffold were characterized by CCK-8 assays,immunostaining and Western blotting.Desirable cell proliferation and phenotypic behaviors were observed.These results have provided an important basis for the next-step in vivo studies of the scaffold,and bode well for its future clinical applications.展开更多
Spinal cord injury often leads to severe motor and sensory deficits,and prognosis using the currently available therapies remains poor.Therefore,we aimed to explore a novel therapeutic approach for improving the progn...Spinal cord injury often leads to severe motor and sensory deficits,and prognosis using the currently available therapies remains poor.Therefore,we aimed to explore a novel therapeutic approach for improving the prognosis of spinal cord injury.In this study,we implanted oscillating field stimulation devices and transplanted neural stem cells into the thoracic region(T9–T10)of rats with a spinal cord contusion.Basso-Beattie-Bresnahan scoring revealed that oscillating field stimulation combined with neural stem cells transplantation promoted motor function recovery following spinal cord injury.In addition,we investigated the regulation of oscillating field stimulation on the miR-124/Tal1 axis in neural stem cells.Transfection of lentivirus was performed to investigate the role of Tal1 in neurogenesis of neural stem cells induced by oscillating field stimulation.Quantitative reverse transcription-polymerase chain reaction,immunofluorescence and western blotting showed that oscillating field stimulation promoted neurogenesis of neural stem cells in vitro and in vivo.Hematoxylin and eosin staining showed that oscillating field stimulation combined with neural stem cells transplantation alleviated cavities formation after spinal cord injury.Taking the results together,we concluded that oscillating field stimulation decreased miR-124 expression and increased Tal1 content,thereby promoting the neurogenesis of neural stem cells.The combination of oscillating field stimulation and neural stem cells transplantation improved neurogenesis,and thereby promoted structural and functional recovery after spinal cord injury.展开更多
To control capillary bleeding, surgeons may use absorbable hemostatic agents, such as Surgicel® and TachoSil®. Due to their slow resorption, their persistence in situ can have a negative impact on tissue rep...To control capillary bleeding, surgeons may use absorbable hemostatic agents, such as Surgicel® and TachoSil®. Due to their slow resorption, their persistence in situ can have a negative impact on tissue repair in the resected organ. To avoid complications and obtain a hemostatic agent that promotes tissue repair, a zinc-supplemented calcium alginate compress was developed: HEMO-IONIC®. This compress is non-absorbable and is therefore removed once hemostasis has been achieved. After demonstrating the hemostatic efficacy and stability of the blood clot obtained with HEMO-IONIC, the impact of Surgicel, TachoSil, and HEMO-IONIC on cell activation and tissue repair were compared (i) in vitro on endothelial cells, which are essential to tissue repair, and (ii) in vivo in a mouse skin excision model. In vitro, only HEMO-IONIC maintained the phenotypic and functional properties of endothelial cells and induced their migration. In comparison, Surgicel was found to be highly cytotoxic, and TachoSil inhibited endothelial cell migration. In vivo, only HEMO-IONIC increased angiogenesis, the recruitment of cells essential to tissue repair (macrophages, fibroblasts, and epithelial cells), and accelerated maturation of the extracellular matrix. These results demonstrate that a zinc-supplemented calcium alginate, HEMO-IONIC, applied for 10 min at the end of surgery and then removed has a long-term positive effect on all phases of tissue repair.展开更多
The repair of lung injury has always been a fundamental problem in the treatment of acute and chronic lung diseases,and more effective treatment approaches have been sought.Regenerative medicine,which gradually repair...The repair of lung injury has always been a fundamental problem in the treatment of acute and chronic lung diseases,and more effective treatment approaches have been sought.Regenerative medicine,which gradually repairs impaired tissue and improves lung function,has been increasingly applied in the field of acute and chronic respiratory diseases.展开更多
Developing advanced biocompatibility materials is of critical importance in biomedical engineering.Polyhydrox-yalkanoates(PHA),being famous for its flexible mechanical properties,thermal properties,biocompatibility,an...Developing advanced biocompatibility materials is of critical importance in biomedical engineering.Polyhydrox-yalkanoates(PHA),being famous for its flexible mechanical properties,thermal properties,biocompatibility,and biodegradability,has been widely used in wound dressings,artificial blood vessels,heart valves,nerve conduits,bone and cartilage scaffolds,surgical sutures,and other fields.However,reports on the application of PHA in tissue repair and regeneration are often lacking in systematics.Here,a comprehensive and in-depth perception of the performance advantages and application value of PHA is provided.In this review,the following applications of PHA in biomedical engineering are covered:i)soft tissue,ii)organ tissue,iii)vascular tissue,iv)heart valve tissue,v)nerve conduit tissue,vi)bone tissue,vii)cartilage tissue and viii)others.Finally,an outlook on the future research directions and challenges of PHA is presented.展开更多
Each year approximately 360,000 people in the United States suffer a peripheral nerve injury （PNI）, which is a leading source of lifelong disability （Kelsey et al., 1997; Noble et al., 1998）. The most frequent cau...Each year approximately 360,000 people in the United States suffer a peripheral nerve injury （PNI）, which is a leading source of lifelong disability （Kelsey et al., 1997; Noble et al., 1998）. The most frequent cause of PNIs is motor vehicle accidents, while gunshot wounds, stabbings, and birth trauma are also common factors. Patients suffering from disabilities as a result of their PNIs are also burdensome to the healthcare system, with aver- age hospital stays of 28 days each year （Kelsey et al., 1997; Noble et al., 1998）.展开更多
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.
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.
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）.
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supported by American Heart Association(AHA)Transformational Project Award(No.23TPA1072337,W.T.)AHA’s Second Century Early Faculty Independence Award(No.23SCEFIA1151841,W.T.)+12 种基金American Society of Transplantation(AST)Career Transition Grant(No.1173492,W.T.)American Lung Association(ALA)Cancer Discovery Award(No.LCD1034625,W.T.)ALA Courtney Cox Cole Lung Cancer Research Award(No.2022A017206,W.T.)Novo Nordisk Validation Award(No.2023A009607,W.T.)Harvard/Brigham Health&Technology Innovation Fund(No.2023A004452,W.T.)Gillian Reny Stepping Strong Center for Trauma Innovation Breakthrough Innovator Award(No.113548)Center for Nanomedicine Research Fund(No.2019A014810,W.T.)Nanotechnology Foundation(No.2022A002721,W.T.)Distinguished Chair Professorship Foundation(No.018129,W.T.)a recipient of the US METAvivor Early Career Investigator Award(No.2018A020560)AHA Collaborative Sciences Award(No.2018A004190)Harvard/Brigham Khoury Innovation Award(No.2020A003219)Department Basic Scientist Grant(No.2420 BPA075).
文摘In the vanguard of biomedical innovation,regenerative medicine emerges as a transformative paradigm,concentrating its efforts on rectifying tissue deficits and functional aberrations in patients through the strategic augmentation of endogenous cellular processes.Central to this approach is nucleic acid therapy,which offers a novel pathway for tissue regeneration by modulating key signaling pathways.As one of the most effective ways to regulate cell function,nucleic acids are crucial for various tissue regeneration;however,their in vivo therapeutic applications face substantial challenges,including nuclease degradation,cell membrane impermeability,and targeted intracellular transport.Biomaterial-based gene delivery systems offer a solution for stable and localized drug delivery by enabling the controlled overexpression of therapeutic nucleic acids,producing functional regulatory agents.This review presents examples of nucleic acid applications in regenerative medicine,highlighting the synergy between nucleic acids and biomaterial technologies.It underlines the importance of nucleic acid delivery techniques,the choice of therapeutic nucleic acids,and biomaterials for advancing tissue repair.The latest developments in designing nucleic acid biomaterial-based delivery vehicles are explored,the mechanism of nucleic acids in tissue regeneration is elucidated,and their limitations are discussed while considering future directions for the clinical translation of nucleic acid-based therapeutics.
基金supported by the National Key R&D Program of China(No.2022YFE0123500)the National Natural Science Foundation of China(Nos.52272304 and 31771081)Science and Technology Commission of Shanghai Municipality(Nos.21ZR1449700,22S31903300,and 22S31900100).
文摘Mineralization has found widespread use in the fabrication of composite biomaterials for hard tissue regeneration.The current mineralization processes are mainly carried out in neutral aqueous solutions of biomineral counter-ions(a pair of cation and anion that form the corresponding minerals at certain conditions),which are stable only at very low concentrations.This typically results in inefficient mineralization and weak control over biomineral formation.Here,we find that,in the organic solvent glycerol,a variety of biomineral counter-ions(e.g.,Ca/PO_(4),Ca/CO_(3),Ca/SO_(4),Mg/PO_(4),or Fe/OH)corresponding to distinct biominerals at significantly high concentrations(up to hundreds-fold greater than those of simulated body fluid(SBF))are able to form translucent and stable solutions(mineralizing solution of highly concentrated counter-ions(MSCIs)),and mineralization can be triggered upon them with external solvents(e.g.,water or ethanol).Furthermore,with pristine bacterial cellulose(BC)membrane as a model,we demonstrate an effective and controllable mineralization performance of MSCIs on organic substrates.This approach not only forms the homogeneous biominerals on the BC fibers and in the interspaces,but also provides regulations over mineralization rate,mineral content,phase,and dopants.The resulting mineralized BC membranes(MBCs)exhibit high cytocompatibility and favor the proliferation of rat bone marrow mesenchymal stem cells(rBMSC).Following this,we prepare a mineralized bone suture(MBS)from MBC for non-weight bearing bone fixation,which then is tested on a rabbit median sternotomy model.It shows firm fixation of the rabbit sternum without causing discernible toxicity or inflammatory response.This study,by extending the mineralization to the organic solution system of highly concentrated counter-ions,develops a promising strategy to design and build targeted mineral-based composites.
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.
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Introduction: The cicatricial acceleration method (MAC®) promotes photobiological effects of an anti-inflammatory and healing nature. Its therapeutic radiation is emitted, producing photobiostimulant effects that result in rapid tissue repair and better tissue quality. The treatment of burns has always been a challenge, which involves both performing surgery and controlling and guiding scar regeneration, avoiding possible morbidities. Objective: To evaluate the effects of applying the MAC methodology with an AlGa (aluminum, gallium arsenide) laser on the time and quality of tissue repair in the skin of rats after induced chemical burns. Method: 22 adult male rats were subjected to a second-degree chemical burn on the back using 50% trichloroacetic acid. After the burns, the animals were randomly separated into 2 groups: control and experimental. The control group (G1) received placebo laser therapy and the laser group (G2) underwent laser irradiation with an energy density of 100 J/cm2. Histological analysis and macroscopic evaluation were carried out by means of the paper template method. Results: Group G1 showed (53%) of the necrosis area and group G2 showed (11%) necrosis area. Conclusion: The cicatricial acceleration method (MAC®) favored the repair of wounds caused by a 2nd-degree chemical burn, optimizing time and improving quality.
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.
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.
基金This work is supported by Key Program of National Nature Science Foundation of China(81030037)Open Fund of State Key Laboratory of Trauma,Burns and Combined Injury,Third Military Medical University(SKLZZ200804).
文摘Adult stem cells are responsible for homeostasis and repair of many tissues.Endogenous adult stem cells reside in certain regions of organs,known as the stem cell niche,which is recognized to have an important role in regulating tissue maintenance and repair.In wound healing and tissue repair,stem cells are mobilized and recruited to the site of wound,and participate in the repair process.Many regulatory factors are involved in the stem cell-based repair process,including stem cell niches and endogenous wound electric fields,which are present at wound tissues and proved to be important in guiding wound healing.Here we briefly review the role of stem cell niches and endogenous electric fields in tissue repair,and hypothesize that endogenous electric fields become part of stem cell niche in the wound site.
基金This study was funded by Ningbo Municipal Bureau of Science and Technology(Grant No.202002N3125).
文摘There has been an increase in the incidence of hypopharyngeal and cervical esophageal cancer worldwide,and hence growing needs for hypopharyngeal and cervical esophageal tissue repair.This work produced a bi-layer composite scaffold with decellularized small intestine submucosa and polylactic-co-glycolic acid,which resembled the layered architectures of its intended tissues.The decellularized small intestine submucosa contained minimal residual DNA(52.5±61.2 ng/mg)and the composite scaffold exhibited satisfactory mechanical properties(a tensile modulus of 21.1±64.8 MPa,an ultimate tensile strength of 14.0±62.9MPa and a failure strain of 26.9±65.1%).The interactions between cells and the respective layers of the scaffold were characterized by CCK-8 assays,immunostaining and Western blotting.Desirable cell proliferation and phenotypic behaviors were observed.These results have provided an important basis for the next-step in vivo studies of the scaffold,and bode well for its future clinical applications.
基金supported by the National Natural Science Foundation of China,Nos.81471273(to JQ),and 81472088(to CLS)the Natural Science Research Projects in Colleges and Universities of Anhui Province,No.KJ2020ZD23(to JQ)the Natural Science Foundation of Anhui Province,No.2208085MH210(to JQ)。
文摘Spinal cord injury often leads to severe motor and sensory deficits,and prognosis using the currently available therapies remains poor.Therefore,we aimed to explore a novel therapeutic approach for improving the prognosis of spinal cord injury.In this study,we implanted oscillating field stimulation devices and transplanted neural stem cells into the thoracic region(T9–T10)of rats with a spinal cord contusion.Basso-Beattie-Bresnahan scoring revealed that oscillating field stimulation combined with neural stem cells transplantation promoted motor function recovery following spinal cord injury.In addition,we investigated the regulation of oscillating field stimulation on the miR-124/Tal1 axis in neural stem cells.Transfection of lentivirus was performed to investigate the role of Tal1 in neurogenesis of neural stem cells induced by oscillating field stimulation.Quantitative reverse transcription-polymerase chain reaction,immunofluorescence and western blotting showed that oscillating field stimulation promoted neurogenesis of neural stem cells in vitro and in vivo.Hematoxylin and eosin staining showed that oscillating field stimulation combined with neural stem cells transplantation alleviated cavities formation after spinal cord injury.Taking the results together,we concluded that oscillating field stimulation decreased miR-124 expression and increased Tal1 content,thereby promoting the neurogenesis of neural stem cells.The combination of oscillating field stimulation and neural stem cells transplantation improved neurogenesis,and thereby promoted structural and functional recovery after spinal cord injury.
基金We are very grateful to Dr.Florence Armstrong for her scientific advice and for participating in supervision of A-C.P.’s PhD research.We also express our gratitude to Dr.C´eline Revenu for her help in writing the article.We thank Dr.Claude Boucheix for his scientific advice and for proofreading of the paper.We are grateful to the UMS-44(ex UMS-33)for providing access to its many platforms,and especially to Denis Clay,who runs the Cytometry platform,as well as the whole team at the animal house.We warmly thank Aurore Devocelle,Antonietta Messina,Nassima Benzoubir,and Marwa Hussein for their help with experiments performed to help answer the reviewers’questions.Finally,we would like to thank the Direction G´en´erale de l’Armement(DGA)which partially financed A-C.P.’s PhD in the context of a CIFRE-D´efense thesis(n◦10/2014/DGA)in particular Dr.Emmanuelle Guillot-Combe,who is responsible for the follow-up of the PhD students.
文摘To control capillary bleeding, surgeons may use absorbable hemostatic agents, such as Surgicel® and TachoSil®. Due to their slow resorption, their persistence in situ can have a negative impact on tissue repair in the resected organ. To avoid complications and obtain a hemostatic agent that promotes tissue repair, a zinc-supplemented calcium alginate compress was developed: HEMO-IONIC®. This compress is non-absorbable and is therefore removed once hemostasis has been achieved. After demonstrating the hemostatic efficacy and stability of the blood clot obtained with HEMO-IONIC, the impact of Surgicel, TachoSil, and HEMO-IONIC on cell activation and tissue repair were compared (i) in vitro on endothelial cells, which are essential to tissue repair, and (ii) in vivo in a mouse skin excision model. In vitro, only HEMO-IONIC maintained the phenotypic and functional properties of endothelial cells and induced their migration. In comparison, Surgicel was found to be highly cytotoxic, and TachoSil inhibited endothelial cell migration. In vivo, only HEMO-IONIC increased angiogenesis, the recruitment of cells essential to tissue repair (macrophages, fibroblasts, and epithelial cells), and accelerated maturation of the extracellular matrix. These results demonstrate that a zinc-supplemented calcium alginate, HEMO-IONIC, applied for 10 min at the end of surgery and then removed has a long-term positive effect on all phases of tissue repair.
基金the Youth Training Program of Military Medical Science and Technology,China(20QNPY099).
文摘The repair of lung injury has always been a fundamental problem in the treatment of acute and chronic lung diseases,and more effective treatment approaches have been sought.Regenerative medicine,which gradually repairs impaired tissue and improves lung function,has been increasingly applied in the field of acute and chronic respiratory diseases.
基金supported by the National Key Research and Development Program of China(2021YFC2101700)the Sun Yat-sen University Clinical Research 5010 Program(No.2017008).
文摘Developing advanced biocompatibility materials is of critical importance in biomedical engineering.Polyhydrox-yalkanoates(PHA),being famous for its flexible mechanical properties,thermal properties,biocompatibility,and biodegradability,has been widely used in wound dressings,artificial blood vessels,heart valves,nerve conduits,bone and cartilage scaffolds,surgical sutures,and other fields.However,reports on the application of PHA in tissue repair and regeneration are often lacking in systematics.Here,a comprehensive and in-depth perception of the performance advantages and application value of PHA is provided.In this review,the following applications of PHA in biomedical engineering are covered:i)soft tissue,ii)organ tissue,iii)vascular tissue,iv)heart valve tissue,v)nerve conduit tissue,vi)bone tissue,vii)cartilage tissue and viii)others.Finally,an outlook on the future research directions and challenges of PHA is presented.
文摘Each year approximately 360,000 people in the United States suffer a peripheral nerve injury （PNI）, which is a leading source of lifelong disability （Kelsey et al., 1997; Noble et al., 1998）. The most frequent cause of PNIs is motor vehicle accidents, while gunshot wounds, stabbings, and birth trauma are also common factors. Patients suffering from disabilities as a result of their PNIs are also burdensome to the healthcare system, with aver- age hospital stays of 28 days each year （Kelsey et al., 1997; Noble et al., 1998）.
