Magnesium(Mg)is the fourth most abundant element in the human body and is important in terms of specific osteogenesis functions.Here,we provide a comprehensive review of the use of magnesium-based biomaterials(MBs)in ...Magnesium(Mg)is the fourth most abundant element in the human body and is important in terms of specific osteogenesis functions.Here,we provide a comprehensive review of the use of magnesium-based biomaterials(MBs)in bone reconstruction.We review the history of MBs and their excellent biocompatibility,biodegradability and osteopromotive properties,highlighting them as candidates for a new generation of biodegradable orthopedic implants.In particular,the results reported in the field-specific literature(280 articles)in recent decades are dissected with respect to the extensive variety of MBs for orthopedic applications,including Mg/Mg alloys,bioglasses,bioceramics,and polymer materials.We also summarize the osteogenic mechanism of MBs,including a detailed section on the physiological process,namely,the enhanced osteogenesis,promotion of osteoblast adhesion and motility,immunomodulation,and enhanced angiogenesis.Moreover,the merits and limitations of current bone grafts and substitutes are compared.The objective of this review is to reveal the strong potential of MBs for their use as agents in bone repair and regeneration and to highlight issues that impede their clinical translation.Finally,the development and challenges of MBs for transplanted orthopedic materials are discussed.展开更多
BACKGROUND： Transplantation of bone marrow-derived mesenchymal stem cells （BMSCs） improves motor functional recovery, but the mechanisms remain unclear. OBJECTIVE： To investigate expression of growth-associated pr...BACKGROUND： Transplantation of bone marrow-derived mesenchymal stem cells （BMSCs） improves motor functional recovery, but the mechanisms remain unclear. OBJECTIVE： To investigate expression of growth-associated protein 43 （GAP-43） and neural cell adhesion molecule following BMSC transplantation to the lateral ventricle in rats with acute focal cerebral ischemic brain damage. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment using immunohistochemistry was performed at the laboratories of Department of Neurology, Renmin Hospital of Wuhan University and Doctoral Scientific Research Work Station of C-BONS PHARMA, Hubei Province, China, from January 2007 to December 2008. MATERIALS： Monoclonal mouse anti-rat 5-bromo-2-deoxyuridine and neural cell adhesion molecule antibodies were purchased from Sigma, USA; monoclonal mouse anti-rat GAP-43 antibody was purchased from Wuhan Boster, China. METHODS： Rat models of right middle cerebral artery occlusion were established using the thread method. At 1 day after middle cerebral artery occlusion, 20μL culture solution, containing 5×10^5 BMSCs, was transplanted to the left lateral ventricle using micro-injection. MAIN OUTCOME MEASURES： Scores of neurological impairment were measured to assess neural function. Expression of GAP-43 and neural cell adhesion molecule at the lesion areas was examined by immunohistochemistry. RESULTS： GAP-43 and neural cell adhesion molecule expression was low in brain tissues of the sham-operated group, but expression increased at the ischemic boundary （P 〈 0.05）. Transplantation of BMSCs further enhanced expression of GAP-43 and neural cell adhesion molecule （P 〈 0.05） and remarkably improved neurological impairment of ischemic rats （P 〈 0.05）. CONCLUSION： BMSC transplantation promoted neurological recovery in rats by upregulating expression of GAP-43 and neural cell adhesion molecule.展开更多
On a woman with severe intrauterine adhesions, hysteroscopy followed by cyclical hormone replacement therapy was tried for 5 months, for development of the endometrium. When this failed, autologous stem cells were tri...On a woman with severe intrauterine adhesions, hysteroscopy followed by cyclical hormone replacement therapy was tried for 5 months, for development of the endometrium. When this failed, autologous stem cells were tried as an alternative therapy. Adult autologous bone marrow mesenchymal stem cells isolated from patient’s own bone marrow and were cultured and placed in the endometrial cavity under ultrasound guidance after curettage. Patient was then given cyclical hormonal therapy. Endometrium was assessed intermittently using ultrasound. Three months later, endometrium partly recovered with improved ultrasonic echo. This resulted in spontaneous pregnancy followed by confirmation of gestational sac, yolk sac, and primitive heart tube pulse on ultrasound. Autologous bone marrow derived mesenchymal stem cells could regenerate injured endometrium not responding to conventional treatment and can be used as an alternative in females with severe Asherman’s syndrome.展开更多
AIM: To investigate the interaction between mesenchymal stem cells (MSCs) and bone grafts using two different cultivation methods: static and dynamic. METHODS: MSCs were isolated from rat bone marrow. MSC culture was ...AIM: To investigate the interaction between mesenchymal stem cells (MSCs) and bone grafts using two different cultivation methods: static and dynamic. METHODS: MSCs were isolated from rat bone marrow. MSC culture was analyzed according to the morphology, cell differentiation potential, and surface molecular markers. Before cell culture, freeze-dried bone (FDB) was maintained in culture for 3 d in order to verify culture medium pH. MSCs were co-cultured with FDB using two different cultivation methods: static co-culture (two-dimensional) and dynamic co-culture (three-dimensional). After 24 h of cultivation by dynamic or static methods, histological analysis of Cell adhesion on FDB was performed. Cell viability was assessed by the Trypan Blue exclusion method on days 0, 3 and 6 after dynamic or static culture. Adherent cells were detached from FDB surface, stained with Trypan Blue, and quantified to determine whether the cells remained on the graft surface in prolonged non-dynamic culture. Statistical analyses were performed with SPSS and a P < 0.05 was considered significant. RESULTS: The results showed a clear potential for adipogenic and osteogenic differentiation of MSC cultures. Rat MSCs were positive for CD44, CD90 and CD29 and negative for CD34, CD45 and CD11bc. FDBs were maintained in culture for 3 d and the results showed there was no significant variation in the culture medium pH with FDB compared to pure medium pH (P > 0.05). In histological analysis, there was a significant difference in the amount of adhered cells on FDB between the two cultivation methods (P < 0.05). The MSCs in the dynamic co-culture method demonstrated greater adhesion on the bone surface than in static co-culture method. On day 0, the cell viability in the dynamic system was significantly higher than in the static system (P < 0.05). There was a statistical difference in cell viability between days 0, 3 and 6 after dynamic culture (P < 0.05). In static culture, cell viability on day 6 was significantly lower than on day 3 and 0 (P < 0.05). CONCLUSION: An alternative cultivation method was developed to improve the MSCs adhesion on FDB, demonstrating that dynamic co-culture provides a superior environment over static conditions.展开更多
Multiple myeloma(MM)is a hematological malignancy characterized by the accumulation of immunoglobulin-secreting clonal plasma cells at the bone marrow(BM).The interaction between MM cells and the BM microenvironment,a...Multiple myeloma(MM)is a hematological malignancy characterized by the accumulation of immunoglobulin-secreting clonal plasma cells at the bone marrow(BM).The interaction between MM cells and the BM microenvironment,and specifically BM mesenchymal stem cells(BM-MSCs),has a key role in the pathophysiology of this disease.Multiple data support the idea that BM-MSCs not only enhance the proliferation and survival of MM cells but are also involved in the resistance of MM cells to certain drugs,aiding the progression of this hematological tumor.The relation of MM cells with the resident BM-MSCs is a two-way interaction.MM modulate the behavior of BM-MSCs altering their expression profile,proliferation rate,osteogenic potential,and expression of senescence markers.In turn,modified BM-MSCs can produce a set of cytokines that would modulate the BM microenvironment to favor disease progression.The interaction between MM cells and BM-MSCs can be mediated by the secretion of a variety of soluble factors and extracellular vesicles carrying microRNAs,long non-coding RNAs or other molecules.However,the communication between these two types of cells could also involve a direct physical interaction through adhesion molecules or tunneling nanotubes.Thus,understanding the way this communication works and developing strategies to interfere in the process,would preclude the expansion of the MM cells and might offer alternative treatments for this incurable disease.展开更多
Intrauterine adhesion is a major cause of female reproductive disorders.Although we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe in...Intrauterine adhesion is a major cause of female reproductive disorders.Although we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe intrauterine adhesion obtain live birth,no large sample randomized controlled studies on this therapeutic strategy in such patients have been reported so far.To verify if the therapy of autologous bone marrow stem cells-scaffold is superior to traditional treatment in moderate to severe intrauterine adhesion patients in increasing their ongoing pregnancy rate,we conducted this randomized controlled clinical trial.Totally 195 participants with moderate to severe intrauterine adhesion were screened and 152 of them were randomly assigned in a 1:1 ratio to either group with autologous bone marrow stem cells-scaffold plus Foley balloon catheter or group with only Foley balloon catheter(control group)from February 2016 to January 2020.The per-protocol analysis included 140 participants:72 in bone marrow stem cells-scaffold group and 68 in control group.The ongoing pregnancy occurred in 45/72(62.5%)participants in the bone marrow stem cells-scaffold group which was significantly higher than that in the control group(28/68,41.2%)(RR=1.52,95%CI 1.08–2.12,P=0.012).The situation was similar in live birth rate(bone marrow stem cells-scaffold group 56.9%(41/72)vs.control group 38.2%(26/68),RR=1.49,95%CI 1.04–2.14,P=0.027).Compared with control group,participants in bone marrow stem cells-scaffold group showed more menstrual blood volume in the 3rd and 6th cycles and maximal endometrial thickness in the 6th cycle after hysteroscopic adhesiolysis.The incidence of mild placenta accrete was increased in bone marrow stem cells-scaffold group and no severe adverse effects were observed.In conclusion,transplantation of bone marrow stem cells-scaffold into uterine cavities of the participants with moderate to severe intrauterine adhesion increased their ongoing pregnancy and live birth rates,and this therapy was relatively safe.展开更多
Bioadhesive hydrogels have demonstrated great potential in bone regeneration.However,the relatively simple adhesion mechanism and lack of intricate structural design restrict their further applications.Herein,inspired...Bioadhesive hydrogels have demonstrated great potential in bone regeneration.However,the relatively simple adhesion mechanism and lack of intricate structural design restrict their further applications.Herein,inspired by multiple adhesion mechanisms of pollen particles and marine mussels,we present a novel type of dual-adhesive hydrogel particles fabricated from microfluidic electrospray for bone regeneration.As the particles are rapidly solidified via liquid nitrogen-assisted cryogelation,they exhibit pollen-mimicking hierarchical porous morphology and gain structure-related adhesion.Besides,the particles are further coated by polydopamine(PDA)to achieve molecular-level adhesion especially to physiological wet surfaces of bone issues.Benefiting from such dual-adhesion mechanisms,the particles can strongly adhere to bone tissue defects,and function as porous scaffolds.Moreover,the dual-adhesive particles can serve as effective vehicles to release key growth factors more than two weeks.In vitro experiments showed that the growth factors-loaden particles have excellent biocompatibility and more significantly promote angiogenesis(~2-fold)and osteogenic differentiation(~3-fold)than control.In vivo experiments indicated that the dual-adhesive particles could significantly enhance bone regeneration(~4-fold)than control by coupling osteogenesis and angiogenesis effects.Based on these features,the bio-inspired dual-adhesive particles have great potentials for bone repair and wound healing applications.展开更多
At present,effective fixation and anti-infection implant materials represent the mainstay for the treatment of open fractures.However,external fixation can cause nail tract infections and is ineffective for fixing sma...At present,effective fixation and anti-infection implant materials represent the mainstay for the treatment of open fractures.However,external fixation can cause nail tract infections and is ineffective for fixing small fracture fragments.Moreover,closed reduction and internal fixation during the early stage of injury can lead to potential bone infection,conducive to bone nonunion and delayed healing.Herein,we designed a bone adhesive with anti-infection,osteogenic and bone adhesion fixation properties to promote reduction and fixation of open fractures and subsequent soft tissue repair.It was prepared by the reaction of gelatin(Gel)and oxidized starch(OS)with vancomycin(VAN)-loaded mesoporous bioactive glass nanoparticles(MBGNs)covalently cross-linked with Schiff bases.Characterization and adhesion experiments were conducted to validate the successful preparation of the Gel-OS/VAN@MBGNs(GOVM-gel)adhesive.Meanwhile,in vitro cell experiments demonstrated its good antibacterial effects with the ability to stimulate bone marrow mesenchymal stem cell(BMSCs)proliferation,upregulate the expression of alkaline phosphatase(ALP)and osteogenic proteins(RunX2 and OPN)and enhance the deposition of calcium nodules.Additionally,we established a rat skull fracture model and a subcutaneous infection model.The histological analysis showed that bone adhesive enhanced osteogenesis,and in vivo experiments demonstrated that the number of inflammatory cells and bacteria was significantly reduced.Overall,the adhesive could promote early reduction of fractures and antibacterial and osteogenic effects,providing the foothold for treatment of this patient population.展开更多
Bone adhesive is a promising material for the treatment of bone fractures,which is helpful for the fast and effective reduction and fixation of broken bones.However,the existing adhesives bond weakly to bone tissues,a...Bone adhesive is a promising material for the treatment of bone fractures,which is helpful for the fast and effective reduction and fixation of broken bones.However,the existing adhesives bond weakly to bone tissues,and are non-absorbable,or hard to cure under wet conditions.Herein,inspired by the cement-based adhesive used in the industry field,we report a bioactive calcium and magnesium phosphate bone adhesive(MPBA)with the properties of facile preparation,robust adhesion,and bioactive.MPBA is equipped with similar strength to cancellous bones and shows reliable bonding performance for various interfaces,such as Ti6Al4V,Al2O3,and poly(ether-ether-ketone).MPBA achieves excellent bonding ability for the above interfaces with the bonding strengths of 2.28±0.47,2.32±0.15,and 1.44±0.38 MPa,respectively.Besides,it also shows reliable fixation ability for bovine bone surfaces.The bonding behavior to materials and bones suggests that MPBA could be used for both fracture treatment and implant fixation.Meanwhile,MPBA possesses good biological activity,which could promote the vascularization process and osteogenic differentiation.Finally,in vivo experiments confirmed MPBA can effectively restore bone strength and promote bone regeneration.展开更多
Schwann cells play an important role in the peripheral nervous system, especially in nerve repair following injury, so artificial nerve regen- eration requires an effective technique for obtaining purified Schwann cel...Schwann cells play an important role in the peripheral nervous system, especially in nerve repair following injury, so artificial nerve regen- eration requires an effective technique for obtaining purified Schwann cells. In vivo and in vitro pre-degeneration of peripheral nerves have been shown to obtain high-purity Schwann cells. We believed that in vitro pre-degeneration was simple and controllable, and available for the clinic. Thus, we co-cultured the crushed sciatic nerves with bone marrow-derived cells in vitro. Results demonstrated that, 3 hours after injury, a large number of mononuclear cells moved to the crushed nerves and a large number of bone marrow-derived cells infiltrated the nerve segments. These changes promoted the degradation of the nerve segments, and the dedifferentiation and proliferation of Schwann cells. Neural cell adhesion molecule and glial fibrillary acidic protein expression were detected in the crushed nerves. Schwann cell yield was 9.08 ± 2.01 ×104/mg. The purity of primary cultured Schwann cells was 88.4 ± 5.79%. These indicate a successful new method for ob- taining Schwann cells of high purity and yield from adult crushed sciatic nerve using bone marrow-derived cells.展开更多
Although hydroxyapatite is commonly used as a scaffold for bone regeneration, sponges may be suitable because of the adaptability to the defect. To use as a scaffold, the fiber of sponge would be coated with any adhes...Although hydroxyapatite is commonly used as a scaffold for bone regeneration, sponges may be suitable because of the adaptability to the defect. To use as a scaffold, the fiber of sponge would be coated with any adhesive to storage stem cells in the sponges. Fiber in the structure of commercially available sponges was coated by immersion in dextran solution and air dried. After seeding of rat bone marrow cells (rBMCs), the sponges were implanted subcutis of rats for estimate osteogenesis in vivo. The level of osteocalcin was 25.28 ±5.71 ng/scaffold and that of Ca was 129.20 ±19.69 μg/scaffold. These values were significantly high- er than those in sponges without dextran coating (p 【0.01). It was thought that rBMCs could be stored on the shelf by dextran deposition in the fiber of the sponge. In vivo examination, dextran induced osteogenesis by rBMCs in many spaces in the inner structure of the sponge.展开更多
基金financial support from the National Natural Science Foundation of China(No.81672230)the Natural Science Foundation of Chongqing(No.cstc2020jcyjmsxm2234)+1 种基金the Top-notch Young Talent Project of Chongqing Traditional Chinese Medicine Hospital(No.CQSZYY2020008)the Chongqing Graduate Research Innovation Project(No.CYS20199)。
文摘Magnesium(Mg)is the fourth most abundant element in the human body and is important in terms of specific osteogenesis functions.Here,we provide a comprehensive review of the use of magnesium-based biomaterials(MBs)in bone reconstruction.We review the history of MBs and their excellent biocompatibility,biodegradability and osteopromotive properties,highlighting them as candidates for a new generation of biodegradable orthopedic implants.In particular,the results reported in the field-specific literature(280 articles)in recent decades are dissected with respect to the extensive variety of MBs for orthopedic applications,including Mg/Mg alloys,bioglasses,bioceramics,and polymer materials.We also summarize the osteogenic mechanism of MBs,including a detailed section on the physiological process,namely,the enhanced osteogenesis,promotion of osteoblast adhesion and motility,immunomodulation,and enhanced angiogenesis.Moreover,the merits and limitations of current bone grafts and substitutes are compared.The objective of this review is to reveal the strong potential of MBs for their use as agents in bone repair and regeneration and to highlight issues that impede their clinical translation.Finally,the development and challenges of MBs for transplanted orthopedic materials are discussed.
文摘BACKGROUND： Transplantation of bone marrow-derived mesenchymal stem cells （BMSCs） improves motor functional recovery, but the mechanisms remain unclear. OBJECTIVE： To investigate expression of growth-associated protein 43 （GAP-43） and neural cell adhesion molecule following BMSC transplantation to the lateral ventricle in rats with acute focal cerebral ischemic brain damage. DESIGN, TIME AND SETTING： A randomized, controlled, animal experiment using immunohistochemistry was performed at the laboratories of Department of Neurology, Renmin Hospital of Wuhan University and Doctoral Scientific Research Work Station of C-BONS PHARMA, Hubei Province, China, from January 2007 to December 2008. MATERIALS： Monoclonal mouse anti-rat 5-bromo-2-deoxyuridine and neural cell adhesion molecule antibodies were purchased from Sigma, USA; monoclonal mouse anti-rat GAP-43 antibody was purchased from Wuhan Boster, China. METHODS： Rat models of right middle cerebral artery occlusion were established using the thread method. At 1 day after middle cerebral artery occlusion, 20μL culture solution, containing 5×10^5 BMSCs, was transplanted to the left lateral ventricle using micro-injection. MAIN OUTCOME MEASURES： Scores of neurological impairment were measured to assess neural function. Expression of GAP-43 and neural cell adhesion molecule at the lesion areas was examined by immunohistochemistry. RESULTS： GAP-43 and neural cell adhesion molecule expression was low in brain tissues of the sham-operated group, but expression increased at the ischemic boundary （P 〈 0.05）. Transplantation of BMSCs further enhanced expression of GAP-43 and neural cell adhesion molecule （P 〈 0.05） and remarkably improved neurological impairment of ischemic rats （P 〈 0.05）. CONCLUSION： BMSC transplantation promoted neurological recovery in rats by upregulating expression of GAP-43 and neural cell adhesion molecule.
文摘On a woman with severe intrauterine adhesions, hysteroscopy followed by cyclical hormone replacement therapy was tried for 5 months, for development of the endometrium. When this failed, autologous stem cells were tried as an alternative therapy. Adult autologous bone marrow mesenchymal stem cells isolated from patient’s own bone marrow and were cultured and placed in the endometrial cavity under ultrasound guidance after curettage. Patient was then given cyclical hormonal therapy. Endometrium was assessed intermittently using ultrasound. Three months later, endometrium partly recovered with improved ultrasonic echo. This resulted in spontaneous pregnancy followed by confirmation of gestational sac, yolk sac, and primitive heart tube pulse on ultrasound. Autologous bone marrow derived mesenchymal stem cells could regenerate injured endometrium not responding to conventional treatment and can be used as an alternative in females with severe Asherman’s syndrome.
基金Supported by Fundo de Incentivo à Pesquisa e Eventos do Hospital de Clínicas de Porto Alegre and Conselho Nacional de Desenvolvimento Científico e Tecnológico(CNPq)
文摘AIM: To investigate the interaction between mesenchymal stem cells (MSCs) and bone grafts using two different cultivation methods: static and dynamic. METHODS: MSCs were isolated from rat bone marrow. MSC culture was analyzed according to the morphology, cell differentiation potential, and surface molecular markers. Before cell culture, freeze-dried bone (FDB) was maintained in culture for 3 d in order to verify culture medium pH. MSCs were co-cultured with FDB using two different cultivation methods: static co-culture (two-dimensional) and dynamic co-culture (three-dimensional). After 24 h of cultivation by dynamic or static methods, histological analysis of Cell adhesion on FDB was performed. Cell viability was assessed by the Trypan Blue exclusion method on days 0, 3 and 6 after dynamic or static culture. Adherent cells were detached from FDB surface, stained with Trypan Blue, and quantified to determine whether the cells remained on the graft surface in prolonged non-dynamic culture. Statistical analyses were performed with SPSS and a P < 0.05 was considered significant. RESULTS: The results showed a clear potential for adipogenic and osteogenic differentiation of MSC cultures. Rat MSCs were positive for CD44, CD90 and CD29 and negative for CD34, CD45 and CD11bc. FDBs were maintained in culture for 3 d and the results showed there was no significant variation in the culture medium pH with FDB compared to pure medium pH (P > 0.05). In histological analysis, there was a significant difference in the amount of adhered cells on FDB between the two cultivation methods (P < 0.05). The MSCs in the dynamic co-culture method demonstrated greater adhesion on the bone surface than in static co-culture method. On day 0, the cell viability in the dynamic system was significantly higher than in the static system (P < 0.05). There was a statistical difference in cell viability between days 0, 3 and 6 after dynamic culture (P < 0.05). In static culture, cell viability on day 6 was significantly lower than on day 3 and 0 (P < 0.05). CONCLUSION: An alternative cultivation method was developed to improve the MSCs adhesion on FDB, demonstrating that dynamic co-culture provides a superior environment over static conditions.
基金Supported by The“Instituto de Salud Carlos III,No.PI22/00264A Predoctoral Program in Biomedicine from The University of Cantabria and The Instituto de Investigación Valdecilla-IDIVAL(Alberto González-González and Daniel García-Sánchez),No.PREVAL19/02,and No.PREVAL20/01“Investigo Program”,part of the“Plan Nacional de Recuperación,Transformación y Resiliencia”from The Spanish Government(Mónica del Dujo-Gutiérrez).
文摘Multiple myeloma(MM)is a hematological malignancy characterized by the accumulation of immunoglobulin-secreting clonal plasma cells at the bone marrow(BM).The interaction between MM cells and the BM microenvironment,and specifically BM mesenchymal stem cells(BM-MSCs),has a key role in the pathophysiology of this disease.Multiple data support the idea that BM-MSCs not only enhance the proliferation and survival of MM cells but are also involved in the resistance of MM cells to certain drugs,aiding the progression of this hematological tumor.The relation of MM cells with the resident BM-MSCs is a two-way interaction.MM modulate the behavior of BM-MSCs altering their expression profile,proliferation rate,osteogenic potential,and expression of senescence markers.In turn,modified BM-MSCs can produce a set of cytokines that would modulate the BM microenvironment to favor disease progression.The interaction between MM cells and BM-MSCs can be mediated by the secretion of a variety of soluble factors and extracellular vesicles carrying microRNAs,long non-coding RNAs or other molecules.However,the communication between these two types of cells could also involve a direct physical interaction through adhesion molecules or tunneling nanotubes.Thus,understanding the way this communication works and developing strategies to interfere in the process,would preclude the expansion of the MM cells and might offer alternative treatments for this incurable disease.
基金This work was supported by the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA16040302,XDA01030505)the National Natural Science Foundation of China(81971336)+1 种基金Jiangsu Provincial Key Medical Center(YXZXB2016004)Jiangsu Provincial Obstetrics and Gynecology Innovation Center(CXZX202229)。
文摘Intrauterine adhesion is a major cause of female reproductive disorders.Although we and others uncontrolled pilot studies showed that treatment with autologous bone marrow stem cells made a few patients with severe intrauterine adhesion obtain live birth,no large sample randomized controlled studies on this therapeutic strategy in such patients have been reported so far.To verify if the therapy of autologous bone marrow stem cells-scaffold is superior to traditional treatment in moderate to severe intrauterine adhesion patients in increasing their ongoing pregnancy rate,we conducted this randomized controlled clinical trial.Totally 195 participants with moderate to severe intrauterine adhesion were screened and 152 of them were randomly assigned in a 1:1 ratio to either group with autologous bone marrow stem cells-scaffold plus Foley balloon catheter or group with only Foley balloon catheter(control group)from February 2016 to January 2020.The per-protocol analysis included 140 participants:72 in bone marrow stem cells-scaffold group and 68 in control group.The ongoing pregnancy occurred in 45/72(62.5%)participants in the bone marrow stem cells-scaffold group which was significantly higher than that in the control group(28/68,41.2%)(RR=1.52,95%CI 1.08–2.12,P=0.012).The situation was similar in live birth rate(bone marrow stem cells-scaffold group 56.9%(41/72)vs.control group 38.2%(26/68),RR=1.49,95%CI 1.04–2.14,P=0.027).Compared with control group,participants in bone marrow stem cells-scaffold group showed more menstrual blood volume in the 3rd and 6th cycles and maximal endometrial thickness in the 6th cycle after hysteroscopic adhesiolysis.The incidence of mild placenta accrete was increased in bone marrow stem cells-scaffold group and no severe adverse effects were observed.In conclusion,transplantation of bone marrow stem cells-scaffold into uterine cavities of the participants with moderate to severe intrauterine adhesion increased their ongoing pregnancy and live birth rates,and this therapy was relatively safe.
基金supported by the National Key Research and Development Program of China(No.2020YFA0908200)the National Natural Science Foundation of China(No.82202670)+2 种基金the Guangdong Basic and Applied Basic Research Foundation(No.2021B1515120054)the Shenzhen Fundamental Research Program(Nos.JCYJ20190813152616459 and JCYJ20210324133214038)the Startup Fund of Wenzhou Institute,University of Chinese Academy of Sciences(No.WIUCASQD2022001).
文摘Bioadhesive hydrogels have demonstrated great potential in bone regeneration.However,the relatively simple adhesion mechanism and lack of intricate structural design restrict their further applications.Herein,inspired by multiple adhesion mechanisms of pollen particles and marine mussels,we present a novel type of dual-adhesive hydrogel particles fabricated from microfluidic electrospray for bone regeneration.As the particles are rapidly solidified via liquid nitrogen-assisted cryogelation,they exhibit pollen-mimicking hierarchical porous morphology and gain structure-related adhesion.Besides,the particles are further coated by polydopamine(PDA)to achieve molecular-level adhesion especially to physiological wet surfaces of bone issues.Benefiting from such dual-adhesion mechanisms,the particles can strongly adhere to bone tissue defects,and function as porous scaffolds.Moreover,the dual-adhesive particles can serve as effective vehicles to release key growth factors more than two weeks.In vitro experiments showed that the growth factors-loaden particles have excellent biocompatibility and more significantly promote angiogenesis(~2-fold)and osteogenic differentiation(~3-fold)than control.In vivo experiments indicated that the dual-adhesive particles could significantly enhance bone regeneration(~4-fold)than control by coupling osteogenesis and angiogenesis effects.Based on these features,the bio-inspired dual-adhesive particles have great potentials for bone repair and wound healing applications.
基金This work was supported by the Guangzhou Science and Technology Program Key Projects(No.202002020001)Science and Technology Planning Project of Guangdong Province(No.2020A0505100039)+1 种基金Autonomous region science and technology branch Xinjiang project plan(No.2022E02040)Clinical Key Specialty in Ningde City,Fujian Province.
文摘At present,effective fixation and anti-infection implant materials represent the mainstay for the treatment of open fractures.However,external fixation can cause nail tract infections and is ineffective for fixing small fracture fragments.Moreover,closed reduction and internal fixation during the early stage of injury can lead to potential bone infection,conducive to bone nonunion and delayed healing.Herein,we designed a bone adhesive with anti-infection,osteogenic and bone adhesion fixation properties to promote reduction and fixation of open fractures and subsequent soft tissue repair.It was prepared by the reaction of gelatin(Gel)and oxidized starch(OS)with vancomycin(VAN)-loaded mesoporous bioactive glass nanoparticles(MBGNs)covalently cross-linked with Schiff bases.Characterization and adhesion experiments were conducted to validate the successful preparation of the Gel-OS/VAN@MBGNs(GOVM-gel)adhesive.Meanwhile,in vitro cell experiments demonstrated its good antibacterial effects with the ability to stimulate bone marrow mesenchymal stem cell(BMSCs)proliferation,upregulate the expression of alkaline phosphatase(ALP)and osteogenic proteins(RunX2 and OPN)and enhance the deposition of calcium nodules.Additionally,we established a rat skull fracture model and a subcutaneous infection model.The histological analysis showed that bone adhesive enhanced osteogenesis,and in vivo experiments demonstrated that the number of inflammatory cells and bacteria was significantly reduced.Overall,the adhesive could promote early reduction of fractures and antibacterial and osteogenic effects,providing the foothold for treatment of this patient population.
基金supported by grants from the National Key Research and Development Program of China(No.2022YFB4601402)the National Natural Science Foundation of China(Nos.32201109,51772233,and 51861145306)+2 种基金the Key Basic Research Program of Shenzhen(No.JCYJ20200109150218836)the Guangdong Basic and Applied Basic Research Foundation(Nos.2022B1515120052 and 2021A1515110557)the Laboratory Self-innovation Research Funding Project of Hanjiang Laboratory(No.HJL202202A002).
文摘Bone adhesive is a promising material for the treatment of bone fractures,which is helpful for the fast and effective reduction and fixation of broken bones.However,the existing adhesives bond weakly to bone tissues,and are non-absorbable,or hard to cure under wet conditions.Herein,inspired by the cement-based adhesive used in the industry field,we report a bioactive calcium and magnesium phosphate bone adhesive(MPBA)with the properties of facile preparation,robust adhesion,and bioactive.MPBA is equipped with similar strength to cancellous bones and shows reliable bonding performance for various interfaces,such as Ti6Al4V,Al2O3,and poly(ether-ether-ketone).MPBA achieves excellent bonding ability for the above interfaces with the bonding strengths of 2.28±0.47,2.32±0.15,and 1.44±0.38 MPa,respectively.Besides,it also shows reliable fixation ability for bovine bone surfaces.The bonding behavior to materials and bones suggests that MPBA could be used for both fracture treatment and implant fixation.Meanwhile,MPBA possesses good biological activity,which could promote the vascularization process and osteogenic differentiation.Finally,in vivo experiments confirmed MPBA can effectively restore bone strength and promote bone regeneration.
基金supported by the Key University Natural Science Research Project of Anhui Province of China,No.KJ2016A870
文摘Schwann cells play an important role in the peripheral nervous system, especially in nerve repair following injury, so artificial nerve regen- eration requires an effective technique for obtaining purified Schwann cells. In vivo and in vitro pre-degeneration of peripheral nerves have been shown to obtain high-purity Schwann cells. We believed that in vitro pre-degeneration was simple and controllable, and available for the clinic. Thus, we co-cultured the crushed sciatic nerves with bone marrow-derived cells in vitro. Results demonstrated that, 3 hours after injury, a large number of mononuclear cells moved to the crushed nerves and a large number of bone marrow-derived cells infiltrated the nerve segments. These changes promoted the degradation of the nerve segments, and the dedifferentiation and proliferation of Schwann cells. Neural cell adhesion molecule and glial fibrillary acidic protein expression were detected in the crushed nerves. Schwann cell yield was 9.08 ± 2.01 ×104/mg. The purity of primary cultured Schwann cells was 88.4 ± 5.79%. These indicate a successful new method for ob- taining Schwann cells of high purity and yield from adult crushed sciatic nerve using bone marrow-derived cells.
文摘Although hydroxyapatite is commonly used as a scaffold for bone regeneration, sponges may be suitable because of the adaptability to the defect. To use as a scaffold, the fiber of sponge would be coated with any adhesive to storage stem cells in the sponges. Fiber in the structure of commercially available sponges was coated by immersion in dextran solution and air dried. After seeding of rat bone marrow cells (rBMCs), the sponges were implanted subcutis of rats for estimate osteogenesis in vivo. The level of osteocalcin was 25.28 ±5.71 ng/scaffold and that of Ca was 129.20 ±19.69 μg/scaffold. These values were significantly high- er than those in sponges without dextran coating (p 【0.01). It was thought that rBMCs could be stored on the shelf by dextran deposition in the fiber of the sponge. In vivo examination, dextran induced osteogenesis by rBMCs in many spaces in the inner structure of the sponge.
