Hypoxic injury(HI)in the prenatal period often causes neonatal neurological disabilities.Due to the difficulty in obtaining clinical samples,the molecular and cellular mechanisms remain unclear.Here we use vascularize...Hypoxic injury(HI)in the prenatal period often causes neonatal neurological disabilities.Due to the difficulty in obtaining clinical samples,the molecular and cellular mechanisms remain unclear.Here we use vascularized cerebral organoids to investigate the hypoxic injury phenotype and explore the intercellular interactions between vascular and neural tissues under hypoxic conditions.Our results indicate that fused vascularized cerebral organoids exhibit broader hypoxic responses and larger decreases in panels of neural development-related genes when exposed to low oxygen levels compared to single cerebral organoids.Interestingly,vessels also exhibit neural protective effects on T-box brain protein 2+intermediate progenitors(IPs),which are markedly lost in HI cerebral organoids.Furthermore,we identify the role of bone morphogenic protein signaling in protecting IPs.Thus,this study has established an in vitro organoid system that can be used to study the contribution of vessels to brain injury under hypoxic conditions and provides a strategy for the identification of intervention targets.展开更多
The regeneration of infected bone defects is still challenging and time-consuming,due to the adverse osteogenic microenvironment caused by bacterial contamination and pronounced ischemia.Biodegradable magnesium(Mg)-ba...The regeneration of infected bone defects is still challenging and time-consuming,due to the adverse osteogenic microenvironment caused by bacterial contamination and pronounced ischemia.Biodegradable magnesium(Mg)-based alloys are desirable for orthopedic implants due to the mechanical properties approximating those of human bone and the released Mg^(2+)ions essential to osteogenic activity.However,the fast and uncontrolled self-degradation of Mg alloy,along with the inadequate antimicrobial activity,limit their strength in the osteogenic microenvironment.Inspired by the structural and physiological characteristics of“fish scales,”two-dimensional(2D)nanomaterials,black phosphorus(BP)and graphene oxide(GO),were assembled together under the action of pulsed electric field.The bionic 2D layered BP/GO nano-coating was constructed for infection resistance,osteogenic microenvironment optimization,and biodegradation control.In the early stage of implantation,it exerted a photothermal effect to ablate bacterial biofilms and avoid contaminating the microenvironment.The blocking effect of the“nano fish scales”-2D material superposition regulated the degradation of implants.In the later stage,it attracted the migration of vascular endothelial cells(VECs)and released phosphate slowly for in situ mineralization to create the microenvironment favoring vascularized bone formation.It is indicated that the enhancement of microtubule deacetylation and cytoskeletal reorganization played a key role in the effect of VEC migration and angiogenesis.This study provided a promising bionic strategy for creating osteogenic microenvironments that match the sequential healing process of infected bone defects.展开更多
Constructing an in vitro vascularized liver tissue model that closely simulates the human liver is crucial for promoting cell proliferation,mimicking physiological heterogeneous structures,and recreating the cellular ...Constructing an in vitro vascularized liver tissue model that closely simulates the human liver is crucial for promoting cell proliferation,mimicking physiological heterogeneous structures,and recreating the cellular microenvironment.However,the layer-by-layer printing method is significantly constrained by the rheological properties of the bioink,making it challenging to form complex three-dimensional vascular structures in low-viscosity soft materials.To overcome this limitation,we developed a cross-linkable biphasic embedding medium by mixing low-viscosity biomaterials with gelatin microgel.This medium possesses yield stress and self-healing properties,facilitating efficient and continuous three-dimensional shaping of sacrificial ink within it.By adjusting the printing speed,we controlled the filament diameter,achieving a range from 250μm to 1000μm,and ensuring precise control over ink deposition locations and filament shapes.Using the in situ endothelialization method,we constructed complex vascular structures and ensured close adhesion between hepatocytes and endothelial cells.In vitro experiments demonstrated that the vascularized liver tissue model exhibited enhanced protein synthesis and metabolic function compared to mixed liver tissue.We also investigated the impact of varying vascular densities on liver tissue function.Transcriptome sequencing revealed that liver tissues with higher vascular density exhibited upregulated gene expression in metabolic and angiogenesis-related pathways.In summary,this method is adaptable to various materials,allowing the rheological properties of the supporting bath and the tissue's porosity to be modified using microgels,thus enabling precise regulation of the liver tissue microenvironment.Additionally,it facilitates the rapid construction of three-dimensional vascular structures within liver tissue.The resulting vascularized liver tissue model exhibits enhanced biological functionality,opening new opportunities for biomedical applications.展开更多
The online version of the original article can be found at:https://www.sciopen.com/article/10.26599/JOTO.2025.9540018 Erratum to Journal of Otology,2025,20(2):123-126.https://doi.org/10.26599/JOTO.2025.9540018 The sur...The online version of the original article can be found at:https://www.sciopen.com/article/10.26599/JOTO.2025.9540018 Erratum to Journal of Otology,2025,20(2):123-126.https://doi.org/10.26599/JOTO.2025.9540018 The surnames and given names of these authors are reversed:Saro-Buendía Miguel,Andresen-Lorca Belén,Pérez-García Alberto,Llópez Carratala Nacho,Carreres Polo Joan,Armengot Carceller Miguel,Perolada Valmaña Jose María.It should be Miguel Saro-Buendía,Belén Andresen-Lorca,Alberto Pérez-García,Nacho Llópez Carratala,Joan Carreres Polo,Miguel Armengot Carceller,Jose María Perolada Valmaña.展开更多
Osteoradionecrosis of the temporal bone(ORN-TB)is usually controlled with conservative measures.However,a temporal bone resection may be required in unresponsive cases.The reconstruction of the resulting defects may b...Osteoradionecrosis of the temporal bone(ORN-TB)is usually controlled with conservative measures.However,a temporal bone resection may be required in unresponsive cases.The reconstruction of the resulting defects may be challenging because of the radiation damage to regional tissues.As a result,distant free flaps may be an optimal choice.For instance,the gracilis muscular free flap(GMFF)has consistent vascular anatomy and can be used to reconstruct small defects.We report three cases of uncontrolled ORN-TB requiring an extensive temporal bone resection followed by vascularized obliteration with a GMFF.The patients reported complete control of the main otologic symptoms(otorrhea,otalgia,and aural fullness)and optimal functional and aesthetic outcomes.Finally,the patients reported significant improvement in quality of life despite early postoperative complications.To our knowledge,the GMFF had not been used to obliterate temporal bone defects in patients with ORN-TB.展开更多
The vascular network is integral to the developmental and metabolic processes of various tissues and functions as a systemic circulatory system that also interconnects organs throughout the body.In this study,we descr...The vascular network is integral to the developmental and metabolic processes of various tissues and functions as a systemic circulatory system that also interconnects organs throughout the body.In this study,we describe a multilayered microfluidic organ-on-a-chip platform designed for reproducing various three-dimensional(3D)vascularized microtissue models for biological applications.This platform utilizes a porous membrane as a physical barrier and leverages capillary action for hydrogel self-filling.Its high flow resistance mitigates the risk of gel bursting into the medium channels and facilitates the delivery of substances to generate a wide range of interstitial flow and biochemical factor concentration gradients.This study demonstrated that this platform can be used to accurately replicate 3D microenvironments for vasculogenesis,angiogenesis,and vascularized tumor modeling.We also investigated the critical role of multiple microenvironmental regulations in vascular formation on a chip.Moreover,we reproduced the process of tumor angiogenesis,including primary solid tumor features and the inhibitory effects of antitumor drugs on tumor growth and tumor vasculature before and after angiogenesis.Hence,our multilayered microfluidic platform is valuable for exploring multiple vascular mechanisms and constructing specific microtissues that closely mimic in vivo physiological conditions,providing new strategies for cancer research.Furthermore,the multilayered configuration improves design flexibility and scalability,providing the potential for a multi-organ interconnected platform for high-throughput drug screening.展开更多
Adequate vascularization is a critical determinant for the successful construction and clinical implementation of complex organotypic tissue models. Currently, low cell and vessel density and insufficient vascular mat...Adequate vascularization is a critical determinant for the successful construction and clinical implementation of complex organotypic tissue models. Currently, low cell and vessel density and insufficient vascular maturation make vascularized organotypic tissue construction difficult,greatly limiting its use in tissue engineering and regenerative medicine. To address these limitations, recent studies have adopted pre-vascularized microtissue assembly for the rapid generation of functional tissue analogs with dense vascular networks and high cell density. In this article, we summarize the development of module assembly-based vascularized organotypic tissue construction and its application in tissue repair and regeneration, organ-scale tissue biomanufacturing, as well as advanced tissue modeling.展开更多
Background:Lymphedema is a debilitating condition that frequently occurs after breast cancer treatment.Vas-cularized lymph node transfer(VLNT)is a promising approach to reduce lymphedema.This study used magnetic reson...Background:Lymphedema is a debilitating condition that frequently occurs after breast cancer treatment.Vas-cularized lymph node transfer(VLNT)is a promising approach to reduce lymphedema.This study used magnetic resonance lymphangiography(MRL)to assess lymphatic reconnections post-VLNT in patients with breast cancer-related lymphedema(BCRL).Methods:The clinical records of six female patients with unilateral upper limb BCRL who underwent VLNT(4 cases)or VLNT combined with breast reconstruction(2 cases)were retrospectively reviewed.All patients were examined using MRL preoperatively and at the 1-year follow-up.The morphological characteristics of the lymphatic network,dermal backflow patterns,and architecture of the lymph nodes were evaluated.Clinical outcomes,patient satisfaction,and complications were assessed.Results:At the 1-year follow-up,reduction in tissue edema and limb circumference was achieved in all six patients.In MRL,the implanted lymph nodes in the axillary region of the affected upper arm were enhanced and visualized in all six patients.Reconnected lymphatic vessels in the subcutaneous tissue associated with the implanted lymph nodes were observed in four patients.Decreased dermal backflow and lymphatic vessel dilation of the affected limbs were observed in all six patients.No disruption of the lymph flow in the donor area was detected.Conclusion:This is the first study to provide direct imaging evidence for the reconnection of afferent lymphatic channels between implanted lymph nodes and the recipient lymphatic system in patients with BCRL.Overall,our study demonstrates the mechanism and efficacy of VLNT in reducing lymphedema.展开更多
Surface modification of microporous bone scaffolds using nanoparticles has been broadly studied in bone tissue engineering.Aiming at improving vascularized bone regeneration(VBR),zeolitic imidazolate framework-8(ZIF-8...Surface modification of microporous bone scaffolds using nanoparticles has been broadly studied in bone tissue engineering.Aiming at improving vascularized bone regeneration(VBR),zeolitic imidazolate framework-8(ZIF-8)was encapsulated with dimethyloxallyl glycine(DMOG)and the drug-carrying nanoparticles(D@Z)could be uniformly coated onto the surface of the bone scaffold.The osteogenic and angiogenic actions of D@Z are closely correlated with the amount of slowly released DMOG,and in general,exhibited a favorable association.Then,the D7.5@Z group,which showed the greatest capacity to induce in vitro osteogenesis-angiogenesis coupling,was utilized for surface modification of the bone scaffold.Biological processes including phosphate-containing compound metabolic process,cell differentiation,cell proliferation and cell motility might contribute to enhanced ability to induce VBR by the coated scaffold and signaling pathways such as Rap1,Ras,phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT)and vascular endothelial growth factor(VEGF)signaling pathways participated in these processes.Finally,as depicted by in vitro real time-polymerase chain reaction(RT-PCR),Western blot(WB)and in vivo cranial bone defect model,the microporous scaffold coated with nano-D7.5@Z greatly promoted VBR.To conclude,nano-D@Z has significant promise for practical application in modification of microporous bone scaffolds to enhance VBR,and DMOG loading quantity has a beneficial influence on D@Z to improve osteogenesis-angiogenesis coupling.展开更多
Dear Editor,Three dimensional(3D)bioprinted extracellular matrix(ECM)can be used to provide both biochemical and biophysical cues to direct mesenchymal stem cells(MSCs)differentiation,and then differentiated cells wer...Dear Editor,Three dimensional(3D)bioprinted extracellular matrix(ECM)can be used to provide both biochemical and biophysical cues to direct mesenchymal stem cells(MSCs)differentiation,and then differentiated cells were isolated for implantation in vivo using surgical procedures.However,the reduced cell activity after cell isolation from 3D constructs and low cell retention in injured sites limit its application[1].Methacrylated gelatin(GelMA)hydrogel has the advantage of fast crosslinking,which could resemble complex architectures of tissue construct in vivo[2].Here,we adopted a noninvasive bioprinting procedure to imitate the regenerative microenvironment that could simultaneously direct the sweat gland(SG)and vascular differentiation from MSCs and ultimately promote the replacement of glandular tissue in situ(Fig.1a).展开更多
The aim of this review is to present and compare the various animal models of vascularized nerve grafts described in the literature as well as to summarize preclinical evidence for superior functional results compared...The aim of this review is to present and compare the various animal models of vascularized nerve grafts described in the literature as well as to summarize preclinical evidence for superior functional results compared to non-vascularized free nerve grafts. We also will present the state of the art on prefabricated vascularized nerve grafts. A systematic literature review on vascularized nerve graft models was conducted via the retrieval with the Pub Med database on March 30, 2019. Data on the animal, nerve, and vascularization model, the recipient bed, the evaluation time points and methods, and the results of the study results were extracted and analyzed from selected articles. The rat sciatic nerve was the most popular model for vascularized nerve grafts, followed by the rabbit;however, rabbit models allow for longer nerve grafts, which are suitable for translational evaluation, and produced more cautious results on the superiority of vascularized nerve grafts. Compared to free nerve grafts, vascularized nerve grafts have better early but similar long-term results, especially in an avascular bed. There are few studies on avascular receiving beds and prefabricated nerve grafts. The clinical translation potential of available animal models is limited, and current experimental knowledge cannot fully support that the differences between vascularized nerve grafts and free nerve grafts yield a clinical advantage that justifies the complexity of the procedure.展开更多
Mandibular defects caused by injuries,tumors,and infections are common and can severely affect mandibular function and the patient's appearance.However,mandible reconstruction with a mandibular bionic structure re...Mandibular defects caused by injuries,tumors,and infections are common and can severely affect mandibular function and the patient's appearance.However,mandible reconstruction with a mandibular bionic structure remains challenging.Inspired by the process of intramembranous ossification in mandibular development,a hierarchical vascularized engineered bone consisting of angiogenesis and osteogenesis modules has been produced.Moreover,the hierarchical vascular network and bone structure generated by these hierarchical vascularized engineered bone modules match the particular anatomical structure of the mandible.The ultra-tough polyion complex has been used as the basic scaffold for hierarchical vascularized engineered bone for ensuring better reconstruction of mandible function.According to the results of in vivo experiments,the bone regenerated using hierarchical vascularized engineered bone is similar to the natural mandibular bone in terms of morphology and genomics.The sonic hedgehog signaling pathway is specifically activated in hierarchical vascularized engineered bone,indicating that the new bone in hierarchical vascularized engineered bone underwent a process of intramembranous ossification identical to that of mandible development.Thus,hierarchical vascularized engineered bone has a high potential for clinical application in mandibular defect reconstruction.Moreover,the concept based on developmental processes and bionic structures provides an effective strategy for tissue regeneration.展开更多
Psychosocial factors are important elements in the assessment and follow-up care for vascularized composite allotransplantation(VCA) and require multidisciplinary evaluation protocols. This review will highlight diffe...Psychosocial factors are important elements in the assessment and follow-up care for vascularized composite allotransplantation(VCA) and require multidisciplinary evaluation protocols. This review will highlight differences between VCA with solid organ transplantation(SOT), provide information on the psychosocial selection of VCA candidates, ethical issues, psychological outcomes, and on the need for multicenter research. VCA is primarily a life-enhancing procedure to improve recipients' quality of life and psychological well-being and it represents a potential option to provide reproduction in case of penile or uterine transplantation. The risk benefit ratio is distinctly different than SOT with candidates desiring life enhancing outcomes including improved body image, return to occupations, restored touch, and for uterine transplant, pregnancy. The Chauvet Workgroup has been convened with membership from a number of transplant centers to address these issues and to call for multicenter research. A multicenter research network would share similar evaluation approaches so that meaningful research on psychosocial variables could inform the transplant community and patients about factors that increase risk of non-adherence and other adverse psychosocial and medical outcomes.展开更多
AIM To look into the management options of early debridement of the wound, followed by vascularized cover to bring in fresh blood supply to remaining tissue in electrical burns. METHODS A total of 16 consecutive patie...AIM To look into the management options of early debridement of the wound, followed by vascularized cover to bring in fresh blood supply to remaining tissue in electrical burns. METHODS A total of 16 consecutive patients sustaining full thickness forearm burns over a period of one year were included in the study group. Debridement was undertaken within 48 h in 13 patients. Three patients were taken for debridement after 48 h. Debridement was repeated within 2-4 d after daily wound assessment and need for further debridement. RESULTS On an average two debridements(range 1-4) was required in our patients for the wound to be ready for definitive cover. Interval between each debridement ranged from 2-18 d. Fourteen patients were provided vascularized cover after final debridement(6 free flaps, 8 pedicled flaps). Functional assessment of gross hand function done at 6 wk, 2 mo, 3 mo and 6 mo follow-up. CONCLUSION High-tension electrical burns lead to significant morbi-dity. These injuries are best managed by early decompression followed by multiple serial debridements. The ideal timing of free flap coverage needs further investigation.展开更多
BACKGROUND Secondary lymphedema after surgical interventions is a progressive,chronic disease that is still not completely curable.Over the past years,a multitude of surgical therapy options have been described.AIM To...BACKGROUND Secondary lymphedema after surgical interventions is a progressive,chronic disease that is still not completely curable.Over the past years,a multitude of surgical therapy options have been described.AIM To summarize the single-center complications in lymph vessel(LVTx)and free vascularized lymph node transfer(VLNT).METHODS In total,the patient collective consisted of 87 patients who were undergoing treatment for secondary leg lymphedema during the study period from March 2010 to April 2020.The data collection was performed preoperatively during consultations,as well as three weeks,six months and twelve months after surgical treatment.In the event of complications,more detailed follow-up checks were carried out.In total n=18 robot-assisted omental lymph node transplantations,n=33 supraclavicular lymph node transplantations and n=36 Lymph vessel transplantations were analyzed.An exemplary drawing is shown in Figure 1.A graphical representation of patient selection is shown in Figure 2.Robotic harvest was performed with the Da Vinci Xi Robot Systems(Intuitive Surgical,CA,United States).RESULTS In total,11 male and 76 female patients were operated on.The mean age of the patients at study entry was:omental VLNT:57.45±8.02 years;supraclavicular VLNT:49.76±4.16 years and LVTx:49.75±4.95 years.The average observation time postoperative was:omental VLNT:18±3.48 mo;supraclavicular VLNT:14.15±4.9 and LVTx:14.84±4.46 mo.In our omental VLNT,three patients showed a slight abdominal sensation of tension within the first 12 postoperative days.No other donor side morbidities occurred.No intraoperative conversion to open technique was needed.Our supraclavicular VLNT collective showed 10 lift defect morbidities with one necessary surgical intervention.In our LVTx collective,12 cases of donor side morbidity were registered.In one case,surgical intervention was necessary.CONCLUSION Concerning donor side morbidity,robot-assisted omental VLNT is clearly superior to supraclavicular lymph node transplantation and LVTx.展开更多
The clinical results of the application of pedicled vascularized bone graft （VBG） from Lister＇s tubercle vs. traditional bone graft （TBG） were evaluated and compared. Thirteen cases of symptomatic scaphoid nonuni...The clinical results of the application of pedicled vascularized bone graft （VBG） from Lister＇s tubercle vs. traditional bone graft （TBG） were evaluated and compared. Thirteen cases of symptomatic scaphoid nonunion were treated between January 2011 and December 2012, including 7 cases subject to VBG and the rest 6 cases to TBG, respectively. Outcomes were assessed by modified Mayo wrist score system. All cases were followed up for an average period of 3.5 months after opera- tion. The results showed that total scores in VBG group were 86.4i9.4 after operation with excellent result in 4 cases, good in 2 and acceptable in one, and those in TBG group were 71.7±9.3 after operation with good result in 2 cases, acceptable in 3 and disappointing in one. Total score of wrist function was significantly improved in VBG group as compared with TBG group （P〈0.05）. Our study suggests that VBG method is more effective for treating scaphoid nonunion than TBG method.展开更多
Objective To find out a new vascularized donor tendon for grafting. Methods A detailed anatomical study olplantaris tendon and its vascular connection with the posterior tibial artery was carried out in 16 legs of 8 f...Objective To find out a new vascularized donor tendon for grafting. Methods A detailed anatomical study olplantaris tendon and its vascular connection with the posterior tibial artery was carried out in 16 legs of 8 fresh adult cadavers, and histological examination of the vascular pattern was also performed. Results There exists a close vascular connection between the crural las cial - linked part of the plantaris tendon and the posterior tibial artery. The blood supply of the plantaris tendon is provided by 2~4 transfasctal branches of the posterior tibial artery in the lower- middle part of leg. Out of these branches, one or two anastomosable arteries (more than 1.0cm) together with veins constantly emerge 5~8cm from the insertion of the plantaris tendon. A strip of Achilles tendon can be a substitute in case of plantaris missing tendon. The histotwical observation demonstrates the reliable vascularity of the paratenon and crural fascial. Conclusion The plantaris tendon is a better option of donor vascularized tendon. A composite tendofascial flap with vascularized pedicle from the posterior tibial artery or its branches is supposed to be an advisable method for vascularized tendon gralt clinically. In the case of the plantaris missing, a strip of Achilles tendon should be the second choice.展开更多
Recently we have been performing biological reconstruction for malignant bone tumors of the extremities using frozen autografts. Here we present a case treated with free vascularized fibular graft (FVFG) after this me...Recently we have been performing biological reconstruction for malignant bone tumors of the extremities using frozen autografts. Here we present a case treated with free vascularized fibular graft (FVFG) after this method. A 23-year-old man developed osteosarcoma in his left distal tibia. There was nonunion after frozen autograft reconstruction, which we treated with FVFG. Twenty-four months later, bridging between the host bone and the frozen autograft was achieved. Our department has achieved bone union in almost all cases, but we sometimes encounter cases of nonunion after this method because of delayed blood supply. In these instances, reconstruction using FVFG may represent an attractive choice for salvage treatment.展开更多
The reconstruction of large scalp and dural defects is difficult. Anterolateral thigh (ALT) flap is now widely used because of its reliable blood supply to the skin paddle. Additionally, ALT can be harvested with a la...The reconstruction of large scalp and dural defects is difficult. Anterolateral thigh (ALT) flap is now widely used because of its reliable blood supply to the skin paddle. Additionally, ALT can be harvested with a large skin paddle and large, well-vascularized fascia. We have successfully treated eight scalp and dural composite defect cases (five male and three female) using ALT with vascularized fascia. The patients’ mean age was 59.1 ± 20.4 years ranging from 31 to 83 years. The mean dural defect size was 73 ± 21 cm<sup>2</sup>, ranging from 50 to 120 cm<sup>2</sup>. There were no postoperative infections, bleeding, cerebrospinal fluid leakage, or meningitis. Further discussion about the usefulness of vascularized fascia may be required and we believe that plastic surgeons, head and neck surgeons, and neurosurgeons should report on the results of dural reconstruction.展开更多
Blood vessels are essential for nutrient and oxygen delivery and waste removal.Scaffold-repairing materials with functional vascular networks are widely used in bone tissue engineering.Additive manufacturing is a manu...Blood vessels are essential for nutrient and oxygen delivery and waste removal.Scaffold-repairing materials with functional vascular networks are widely used in bone tissue engineering.Additive manufacturing is a manufacturing technology that creates three-dimensional solids by stacking substances layer by layer,mainly including but not limited to 3D printing,but also 4D printing,5D printing and 6D printing.It can be effectively combined with vascularization to meet the needs of vascularized tissue scaffolds by precisely tuning the mechanical structure and biological properties of smart vascular scaffolds.Herein,the development of neovascularization to vascularization to bone tissue engineering is systematically discussed in terms of the importance of vascularization to the tissue.Additionally,the research progress and future prospects of vascularized 3D printed scaffold materials are highlighted and presented in four categories:functional vascularized 3D printed scaffolds,cell-based vascularized 3D printed scaffolds,vascularized 3D printed scaffolds loaded with specific carriers and bionic vascularized 3D printed scaffolds.Finally,a brief review of vascularized additive manufacturing-tissue scaffolds in related tissues such as the vascular tissue engineering,cardiovascular system,skeletal muscle,soft tissue and a discussion of the challenges and development efforts leading to significant advances in intelligent vascularized tissue regeneration is presented.展开更多
基金supported by the National Key Research and Development Program of China(2024YFA1108000 and 2021ZD0202500)the National Natural Science Foundation of China(32130035 and 92168107)+2 种基金the Joint Project of the Yangtze River Delta Science and Technology Innovation Community(2024CSJZN0600)the Central Guidance on Local Science and Technology Development Fund(YDZX20233100001002)the Shanghai Frontiers Science Center for Biomacromolecules and Precision Medicine at Shanghai Tech University.
文摘Hypoxic injury(HI)in the prenatal period often causes neonatal neurological disabilities.Due to the difficulty in obtaining clinical samples,the molecular and cellular mechanisms remain unclear.Here we use vascularized cerebral organoids to investigate the hypoxic injury phenotype and explore the intercellular interactions between vascular and neural tissues under hypoxic conditions.Our results indicate that fused vascularized cerebral organoids exhibit broader hypoxic responses and larger decreases in panels of neural development-related genes when exposed to low oxygen levels compared to single cerebral organoids.Interestingly,vessels also exhibit neural protective effects on T-box brain protein 2+intermediate progenitors(IPs),which are markedly lost in HI cerebral organoids.Furthermore,we identify the role of bone morphogenic protein signaling in protecting IPs.Thus,this study has established an in vitro organoid system that can be used to study the contribution of vessels to brain injury under hypoxic conditions and provides a strategy for the identification of intervention targets.
基金supported by the National Natural Science Foundation of China[81801007]the Traditional Chinese Medicine Bureau of Guangdong Province[20242062]+2 种基金the Major of Basic and Applied Basic Research Project of Guangzhou City[202201011601]the Science and Cultivation Foundation of Stomatological Hospital of Southern Medical University[PY2021016]the Guangdong Province Clinical Teaching Base Teaching Reform Research Project[2023JD054].
文摘The regeneration of infected bone defects is still challenging and time-consuming,due to the adverse osteogenic microenvironment caused by bacterial contamination and pronounced ischemia.Biodegradable magnesium(Mg)-based alloys are desirable for orthopedic implants due to the mechanical properties approximating those of human bone and the released Mg^(2+)ions essential to osteogenic activity.However,the fast and uncontrolled self-degradation of Mg alloy,along with the inadequate antimicrobial activity,limit their strength in the osteogenic microenvironment.Inspired by the structural and physiological characteristics of“fish scales,”two-dimensional(2D)nanomaterials,black phosphorus(BP)and graphene oxide(GO),were assembled together under the action of pulsed electric field.The bionic 2D layered BP/GO nano-coating was constructed for infection resistance,osteogenic microenvironment optimization,and biodegradation control.In the early stage of implantation,it exerted a photothermal effect to ablate bacterial biofilms and avoid contaminating the microenvironment.The blocking effect of the“nano fish scales”-2D material superposition regulated the degradation of implants.In the later stage,it attracted the migration of vascular endothelial cells(VECs)and released phosphate slowly for in situ mineralization to create the microenvironment favoring vascularized bone formation.It is indicated that the enhancement of microtubule deacetylation and cytoskeletal reorganization played a key role in the effect of VEC migration and angiogenesis.This study provided a promising bionic strategy for creating osteogenic microenvironments that match the sequential healing process of infected bone defects.
基金the funding from the National Natural Science Foundation of China No.52275294the National Key Research and Development Program of China(No.2018YFA0703000)。
文摘Constructing an in vitro vascularized liver tissue model that closely simulates the human liver is crucial for promoting cell proliferation,mimicking physiological heterogeneous structures,and recreating the cellular microenvironment.However,the layer-by-layer printing method is significantly constrained by the rheological properties of the bioink,making it challenging to form complex three-dimensional vascular structures in low-viscosity soft materials.To overcome this limitation,we developed a cross-linkable biphasic embedding medium by mixing low-viscosity biomaterials with gelatin microgel.This medium possesses yield stress and self-healing properties,facilitating efficient and continuous three-dimensional shaping of sacrificial ink within it.By adjusting the printing speed,we controlled the filament diameter,achieving a range from 250μm to 1000μm,and ensuring precise control over ink deposition locations and filament shapes.Using the in situ endothelialization method,we constructed complex vascular structures and ensured close adhesion between hepatocytes and endothelial cells.In vitro experiments demonstrated that the vascularized liver tissue model exhibited enhanced protein synthesis and metabolic function compared to mixed liver tissue.We also investigated the impact of varying vascular densities on liver tissue function.Transcriptome sequencing revealed that liver tissues with higher vascular density exhibited upregulated gene expression in metabolic and angiogenesis-related pathways.In summary,this method is adaptable to various materials,allowing the rheological properties of the supporting bath and the tissue's porosity to be modified using microgels,thus enabling precise regulation of the liver tissue microenvironment.Additionally,it facilitates the rapid construction of three-dimensional vascular structures within liver tissue.The resulting vascularized liver tissue model exhibits enhanced biological functionality,opening new opportunities for biomedical applications.
文摘The online version of the original article can be found at:https://www.sciopen.com/article/10.26599/JOTO.2025.9540018 Erratum to Journal of Otology,2025,20(2):123-126.https://doi.org/10.26599/JOTO.2025.9540018 The surnames and given names of these authors are reversed:Saro-Buendía Miguel,Andresen-Lorca Belén,Pérez-García Alberto,Llópez Carratala Nacho,Carreres Polo Joan,Armengot Carceller Miguel,Perolada Valmaña Jose María.It should be Miguel Saro-Buendía,Belén Andresen-Lorca,Alberto Pérez-García,Nacho Llópez Carratala,Joan Carreres Polo,Miguel Armengot Carceller,Jose María Perolada Valmaña.
文摘Osteoradionecrosis of the temporal bone(ORN-TB)is usually controlled with conservative measures.However,a temporal bone resection may be required in unresponsive cases.The reconstruction of the resulting defects may be challenging because of the radiation damage to regional tissues.As a result,distant free flaps may be an optimal choice.For instance,the gracilis muscular free flap(GMFF)has consistent vascular anatomy and can be used to reconstruct small defects.We report three cases of uncontrolled ORN-TB requiring an extensive temporal bone resection followed by vascularized obliteration with a GMFF.The patients reported complete control of the main otologic symptoms(otorrhea,otalgia,and aural fullness)and optimal functional and aesthetic outcomes.Finally,the patients reported significant improvement in quality of life despite early postoperative complications.To our knowledge,the GMFF had not been used to obliterate temporal bone defects in patients with ORN-TB.
基金supported by grants from the Interdisciplinary Program of Shanghai Jiao Tong University (No. YG2023LC04)the National Natural Science Foundation of China (Nos. 32471473, 62231025, and 82171011)+1 种基金the Research Program of Shanghai Science and Technology Committee (Nos. 24141900900 and 25JC3201100)Chongqing Natural Science Foundation (No. CSTB2022NSCQ-MSX0767)
文摘The vascular network is integral to the developmental and metabolic processes of various tissues and functions as a systemic circulatory system that also interconnects organs throughout the body.In this study,we describe a multilayered microfluidic organ-on-a-chip platform designed for reproducing various three-dimensional(3D)vascularized microtissue models for biological applications.This platform utilizes a porous membrane as a physical barrier and leverages capillary action for hydrogel self-filling.Its high flow resistance mitigates the risk of gel bursting into the medium channels and facilitates the delivery of substances to generate a wide range of interstitial flow and biochemical factor concentration gradients.This study demonstrated that this platform can be used to accurately replicate 3D microenvironments for vasculogenesis,angiogenesis,and vascularized tumor modeling.We also investigated the critical role of multiple microenvironmental regulations in vascular formation on a chip.Moreover,we reproduced the process of tumor angiogenesis,including primary solid tumor features and the inhibitory effects of antitumor drugs on tumor growth and tumor vasculature before and after angiogenesis.Hence,our multilayered microfluidic platform is valuable for exploring multiple vascular mechanisms and constructing specific microtissues that closely mimic in vivo physiological conditions,providing new strategies for cancer research.Furthermore,the multilayered configuration improves design flexibility and scalability,providing the potential for a multi-organ interconnected platform for high-throughput drug screening.
文摘Adequate vascularization is a critical determinant for the successful construction and clinical implementation of complex organotypic tissue models. Currently, low cell and vessel density and insufficient vascular maturation make vascularized organotypic tissue construction difficult,greatly limiting its use in tissue engineering and regenerative medicine. To address these limitations, recent studies have adopted pre-vascularized microtissue assembly for the rapid generation of functional tissue analogs with dense vascular networks and high cell density. In this article, we summarize the development of module assembly-based vascularized organotypic tissue construction and its application in tissue repair and regeneration, organ-scale tissue biomanufacturing, as well as advanced tissue modeling.
基金supported by the National Natural Science Foundation of China(grant nos.81372080 and 82302822)Shanghai Municipal Key Clinical Specialty(grant no.shslczdzk00901)Shanghai Sailing Program(grant no.21YF1424000).
文摘Background:Lymphedema is a debilitating condition that frequently occurs after breast cancer treatment.Vas-cularized lymph node transfer(VLNT)is a promising approach to reduce lymphedema.This study used magnetic resonance lymphangiography(MRL)to assess lymphatic reconnections post-VLNT in patients with breast cancer-related lymphedema(BCRL).Methods:The clinical records of six female patients with unilateral upper limb BCRL who underwent VLNT(4 cases)or VLNT combined with breast reconstruction(2 cases)were retrospectively reviewed.All patients were examined using MRL preoperatively and at the 1-year follow-up.The morphological characteristics of the lymphatic network,dermal backflow patterns,and architecture of the lymph nodes were evaluated.Clinical outcomes,patient satisfaction,and complications were assessed.Results:At the 1-year follow-up,reduction in tissue edema and limb circumference was achieved in all six patients.In MRL,the implanted lymph nodes in the axillary region of the affected upper arm were enhanced and visualized in all six patients.Reconnected lymphatic vessels in the subcutaneous tissue associated with the implanted lymph nodes were observed in four patients.Decreased dermal backflow and lymphatic vessel dilation of the affected limbs were observed in all six patients.No disruption of the lymph flow in the donor area was detected.Conclusion:This is the first study to provide direct imaging evidence for the reconnection of afferent lymphatic channels between implanted lymph nodes and the recipient lymphatic system in patients with BCRL.Overall,our study demonstrates the mechanism and efficacy of VLNT in reducing lymphedema.
基金supported by the National Natural Science Foundation of China(Nos.82201128,82271034)Special Funding for Post-doctoral Research Projects in Sichuan Province(No.TB2022045)+2 种基金Sichuan Province Science and Technology Plan Projects(No.23NSFSC1723)China Postdoctoral Science Foundation(No.2022M722250)Research and Development Program(West China Hospital of Stomatology Sichuan University)(Nos.RD-02–2022012,RD-03–202107)。
文摘Surface modification of microporous bone scaffolds using nanoparticles has been broadly studied in bone tissue engineering.Aiming at improving vascularized bone regeneration(VBR),zeolitic imidazolate framework-8(ZIF-8)was encapsulated with dimethyloxallyl glycine(DMOG)and the drug-carrying nanoparticles(D@Z)could be uniformly coated onto the surface of the bone scaffold.The osteogenic and angiogenic actions of D@Z are closely correlated with the amount of slowly released DMOG,and in general,exhibited a favorable association.Then,the D7.5@Z group,which showed the greatest capacity to induce in vitro osteogenesis-angiogenesis coupling,was utilized for surface modification of the bone scaffold.Biological processes including phosphate-containing compound metabolic process,cell differentiation,cell proliferation and cell motility might contribute to enhanced ability to induce VBR by the coated scaffold and signaling pathways such as Rap1,Ras,phosphatidylinositol 3-kinase/protein kinase B(PI3K-AKT)and vascular endothelial growth factor(VEGF)signaling pathways participated in these processes.Finally,as depicted by in vitro real time-polymerase chain reaction(RT-PCR),Western blot(WB)and in vivo cranial bone defect model,the microporous scaffold coated with nano-D7.5@Z greatly promoted VBR.To conclude,nano-D@Z has significant promise for practical application in modification of microporous bone scaffolds to enhance VBR,and DMOG loading quantity has a beneficial influence on D@Z to improve osteogenesis-angiogenesis coupling.
基金supported by the Science Fund for National Defense Distinguished Young Scholars(2022-JCJQ-ZQ-016)the Key Basic Research Projects of the Foundation Strengthening Plan(2022-JCJQZD-096-00)+2 种基金the National Key Research and Development Program of China(2022YFA1104604)the National Natural Science Foundation of China(32000969)the Key Support Program for Growth Factor Research(SZYZ-TR-03).
文摘Dear Editor,Three dimensional(3D)bioprinted extracellular matrix(ECM)can be used to provide both biochemical and biophysical cues to direct mesenchymal stem cells(MSCs)differentiation,and then differentiated cells were isolated for implantation in vivo using surgical procedures.However,the reduced cell activity after cell isolation from 3D constructs and low cell retention in injured sites limit its application[1].Methacrylated gelatin(GelMA)hydrogel has the advantage of fast crosslinking,which could resemble complex architectures of tissue construct in vivo[2].Here,we adopted a noninvasive bioprinting procedure to imitate the regenerative microenvironment that could simultaneously direct the sweat gland(SG)and vascular differentiation from MSCs and ultimately promote the replacement of glandular tissue in situ(Fig.1a).
文摘The aim of this review is to present and compare the various animal models of vascularized nerve grafts described in the literature as well as to summarize preclinical evidence for superior functional results compared to non-vascularized free nerve grafts. We also will present the state of the art on prefabricated vascularized nerve grafts. A systematic literature review on vascularized nerve graft models was conducted via the retrieval with the Pub Med database on March 30, 2019. Data on the animal, nerve, and vascularization model, the recipient bed, the evaluation time points and methods, and the results of the study results were extracted and analyzed from selected articles. The rat sciatic nerve was the most popular model for vascularized nerve grafts, followed by the rabbit;however, rabbit models allow for longer nerve grafts, which are suitable for translational evaluation, and produced more cautious results on the superiority of vascularized nerve grafts. Compared to free nerve grafts, vascularized nerve grafts have better early but similar long-term results, especially in an avascular bed. There are few studies on avascular receiving beds and prefabricated nerve grafts. The clinical translation potential of available animal models is limited, and current experimental knowledge cannot fully support that the differences between vascularized nerve grafts and free nerve grafts yield a clinical advantage that justifies the complexity of the procedure.
基金National Key Research and Development Program of China(2018YFA0703000)National Natural Science Foundation of China(8212200044,52075482,82071085,81873720)+2 种基金Zhejiang Provincial Natural Science Foundation of China(LR21H140001)Key Research and Development Program of Zhejiang,China(2017C01054,2018C03062)Scientific Research Fund of Zhejiang Provincial Education Department(Y202045564)。
文摘Mandibular defects caused by injuries,tumors,and infections are common and can severely affect mandibular function and the patient's appearance.However,mandible reconstruction with a mandibular bionic structure remains challenging.Inspired by the process of intramembranous ossification in mandibular development,a hierarchical vascularized engineered bone consisting of angiogenesis and osteogenesis modules has been produced.Moreover,the hierarchical vascular network and bone structure generated by these hierarchical vascularized engineered bone modules match the particular anatomical structure of the mandible.The ultra-tough polyion complex has been used as the basic scaffold for hierarchical vascularized engineered bone for ensuring better reconstruction of mandible function.According to the results of in vivo experiments,the bone regenerated using hierarchical vascularized engineered bone is similar to the natural mandibular bone in terms of morphology and genomics.The sonic hedgehog signaling pathway is specifically activated in hierarchical vascularized engineered bone,indicating that the new bone in hierarchical vascularized engineered bone underwent a process of intramembranous ossification identical to that of mandible development.Thus,hierarchical vascularized engineered bone has a high potential for clinical application in mandibular defect reconstruction.Moreover,the concept based on developmental processes and bionic structures provides an effective strategy for tissue regeneration.
基金Supported by The Tirol Kliniken,Innsbruck,Austria
文摘Psychosocial factors are important elements in the assessment and follow-up care for vascularized composite allotransplantation(VCA) and require multidisciplinary evaluation protocols. This review will highlight differences between VCA with solid organ transplantation(SOT), provide information on the psychosocial selection of VCA candidates, ethical issues, psychological outcomes, and on the need for multicenter research. VCA is primarily a life-enhancing procedure to improve recipients' quality of life and psychological well-being and it represents a potential option to provide reproduction in case of penile or uterine transplantation. The risk benefit ratio is distinctly different than SOT with candidates desiring life enhancing outcomes including improved body image, return to occupations, restored touch, and for uterine transplant, pregnancy. The Chauvet Workgroup has been convened with membership from a number of transplant centers to address these issues and to call for multicenter research. A multicenter research network would share similar evaluation approaches so that meaningful research on psychosocial variables could inform the transplant community and patients about factors that increase risk of non-adherence and other adverse psychosocial and medical outcomes.
文摘AIM To look into the management options of early debridement of the wound, followed by vascularized cover to bring in fresh blood supply to remaining tissue in electrical burns. METHODS A total of 16 consecutive patients sustaining full thickness forearm burns over a period of one year were included in the study group. Debridement was undertaken within 48 h in 13 patients. Three patients were taken for debridement after 48 h. Debridement was repeated within 2-4 d after daily wound assessment and need for further debridement. RESULTS On an average two debridements(range 1-4) was required in our patients for the wound to be ready for definitive cover. Interval between each debridement ranged from 2-18 d. Fourteen patients were provided vascularized cover after final debridement(6 free flaps, 8 pedicled flaps). Functional assessment of gross hand function done at 6 wk, 2 mo, 3 mo and 6 mo follow-up. CONCLUSION High-tension electrical burns lead to significant morbi-dity. These injuries are best managed by early decompression followed by multiple serial debridements. The ideal timing of free flap coverage needs further investigation.
文摘BACKGROUND Secondary lymphedema after surgical interventions is a progressive,chronic disease that is still not completely curable.Over the past years,a multitude of surgical therapy options have been described.AIM To summarize the single-center complications in lymph vessel(LVTx)and free vascularized lymph node transfer(VLNT).METHODS In total,the patient collective consisted of 87 patients who were undergoing treatment for secondary leg lymphedema during the study period from March 2010 to April 2020.The data collection was performed preoperatively during consultations,as well as three weeks,six months and twelve months after surgical treatment.In the event of complications,more detailed follow-up checks were carried out.In total n=18 robot-assisted omental lymph node transplantations,n=33 supraclavicular lymph node transplantations and n=36 Lymph vessel transplantations were analyzed.An exemplary drawing is shown in Figure 1.A graphical representation of patient selection is shown in Figure 2.Robotic harvest was performed with the Da Vinci Xi Robot Systems(Intuitive Surgical,CA,United States).RESULTS In total,11 male and 76 female patients were operated on.The mean age of the patients at study entry was:omental VLNT:57.45±8.02 years;supraclavicular VLNT:49.76±4.16 years and LVTx:49.75±4.95 years.The average observation time postoperative was:omental VLNT:18±3.48 mo;supraclavicular VLNT:14.15±4.9 and LVTx:14.84±4.46 mo.In our omental VLNT,three patients showed a slight abdominal sensation of tension within the first 12 postoperative days.No other donor side morbidities occurred.No intraoperative conversion to open technique was needed.Our supraclavicular VLNT collective showed 10 lift defect morbidities with one necessary surgical intervention.In our LVTx collective,12 cases of donor side morbidity were registered.In one case,surgical intervention was necessary.CONCLUSION Concerning donor side morbidity,robot-assisted omental VLNT is clearly superior to supraclavicular lymph node transplantation and LVTx.
文摘The clinical results of the application of pedicled vascularized bone graft （VBG） from Lister＇s tubercle vs. traditional bone graft （TBG） were evaluated and compared. Thirteen cases of symptomatic scaphoid nonunion were treated between January 2011 and December 2012, including 7 cases subject to VBG and the rest 6 cases to TBG, respectively. Outcomes were assessed by modified Mayo wrist score system. All cases were followed up for an average period of 3.5 months after opera- tion. The results showed that total scores in VBG group were 86.4i9.4 after operation with excellent result in 4 cases, good in 2 and acceptable in one, and those in TBG group were 71.7±9.3 after operation with good result in 2 cases, acceptable in 3 and disappointing in one. Total score of wrist function was significantly improved in VBG group as compared with TBG group （P〈0.05）. Our study suggests that VBG method is more effective for treating scaphoid nonunion than TBG method.
文摘Objective To find out a new vascularized donor tendon for grafting. Methods A detailed anatomical study olplantaris tendon and its vascular connection with the posterior tibial artery was carried out in 16 legs of 8 fresh adult cadavers, and histological examination of the vascular pattern was also performed. Results There exists a close vascular connection between the crural las cial - linked part of the plantaris tendon and the posterior tibial artery. The blood supply of the plantaris tendon is provided by 2~4 transfasctal branches of the posterior tibial artery in the lower- middle part of leg. Out of these branches, one or two anastomosable arteries (more than 1.0cm) together with veins constantly emerge 5~8cm from the insertion of the plantaris tendon. A strip of Achilles tendon can be a substitute in case of plantaris missing tendon. The histotwical observation demonstrates the reliable vascularity of the paratenon and crural fascial. Conclusion The plantaris tendon is a better option of donor vascularized tendon. A composite tendofascial flap with vascularized pedicle from the posterior tibial artery or its branches is supposed to be an advisable method for vascularized tendon gralt clinically. In the case of the plantaris missing, a strip of Achilles tendon should be the second choice.
文摘Recently we have been performing biological reconstruction for malignant bone tumors of the extremities using frozen autografts. Here we present a case treated with free vascularized fibular graft (FVFG) after this method. A 23-year-old man developed osteosarcoma in his left distal tibia. There was nonunion after frozen autograft reconstruction, which we treated with FVFG. Twenty-four months later, bridging between the host bone and the frozen autograft was achieved. Our department has achieved bone union in almost all cases, but we sometimes encounter cases of nonunion after this method because of delayed blood supply. In these instances, reconstruction using FVFG may represent an attractive choice for salvage treatment.
文摘The reconstruction of large scalp and dural defects is difficult. Anterolateral thigh (ALT) flap is now widely used because of its reliable blood supply to the skin paddle. Additionally, ALT can be harvested with a large skin paddle and large, well-vascularized fascia. We have successfully treated eight scalp and dural composite defect cases (five male and three female) using ALT with vascularized fascia. The patients’ mean age was 59.1 ± 20.4 years ranging from 31 to 83 years. The mean dural defect size was 73 ± 21 cm<sup>2</sup>, ranging from 50 to 120 cm<sup>2</sup>. There were no postoperative infections, bleeding, cerebrospinal fluid leakage, or meningitis. Further discussion about the usefulness of vascularized fascia may be required and we believe that plastic surgeons, head and neck surgeons, and neurosurgeons should report on the results of dural reconstruction.
基金supported by grants from the National Key Research and Development Program of China (2020YFA0908200)Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support (20171906)+2 种基金Shanghai Municipal Health and Family Planning Commission (2022XD055)Natural Science Foundation of Shandong Province (Shandong) (ZR2020QH121)GuangCi Professorship Program of Ruijin Hospital Shanghai Jiao Tong University School of Medicine
文摘Blood vessels are essential for nutrient and oxygen delivery and waste removal.Scaffold-repairing materials with functional vascular networks are widely used in bone tissue engineering.Additive manufacturing is a manufacturing technology that creates three-dimensional solids by stacking substances layer by layer,mainly including but not limited to 3D printing,but also 4D printing,5D printing and 6D printing.It can be effectively combined with vascularization to meet the needs of vascularized tissue scaffolds by precisely tuning the mechanical structure and biological properties of smart vascular scaffolds.Herein,the development of neovascularization to vascularization to bone tissue engineering is systematically discussed in terms of the importance of vascularization to the tissue.Additionally,the research progress and future prospects of vascularized 3D printed scaffold materials are highlighted and presented in four categories:functional vascularized 3D printed scaffolds,cell-based vascularized 3D printed scaffolds,vascularized 3D printed scaffolds loaded with specific carriers and bionic vascularized 3D printed scaffolds.Finally,a brief review of vascularized additive manufacturing-tissue scaffolds in related tissues such as the vascular tissue engineering,cardiovascular system,skeletal muscle,soft tissue and a discussion of the challenges and development efforts leading to significant advances in intelligent vascularized tissue regeneration is presented.
