High quality repair of osteochondral defects in rats using the extracellular matrix of antler stem cells

BACKGROUND Cartilage defects are some of the most common causes of arthritis.Cartilage lesions caused by inflammation,trauma or degenerative disease normally result in osteochondral defects.Previous studies have shown that decellularized extracellular matrix(ECM)derived from autologous,allogenic,or xenogeneic mesenchymal stromal cells(MSCs)can effectively restore osteochondral integrity.AIM To determine whether the decellularized ECM of antler reserve mesenchymal cells(RMCs),a xenogeneic material from antler stem cells,is superior to the currently available treatments for osteochondral defects.METHODS We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70%confluence;50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition.Decellularized sheets of adipocyte-derived MSCs(aMSCs)and antlerogenic periosteal cells(another type of antler stem cells)were used as the controls.Three weeks after ascorbic acid stimulation,the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints.RESULTS The defects were successfully repaired by applying the ECM-sheets.The highest quality of repair was achieved in the RMC-ECM group both in vitro(including cell attachment and proliferation),and in vivo(including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues).Notably,the antler-stem-cell-derived ECM(xenogeneic)performed better than the aMSC-ECM(allogenic),while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells.CONCLUSION Decellularized xenogeneic ECM derived from the antler stem cell,particularly the active form(RMC-ECM),can achieve high quality repair/reconstruction of osteochondral defects,suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.

Research progress on the characterization and repair of graphene defects

Graphene has excellent theoretical properties and a wide range of applications in metal-based composites. However, because of defects on the graphene surface, the actual performance of the material is far below theoretical expectations. In addition, graphene containing defects could easily react with a matrix alloy, such as Al, to generate brittle and hydrolyzed phases that could further reduce the performance of the resulting composite. Therefore, defect repair is an important area of graphene research. The repair methods reported in the present paper include chemical vapor deposition, doping, liquid-phase repair, external energy graphitization, and alloying. Detailed analyses and comparisons of these methods are carried out, and the characterization methods of graphene are introduced. The mechanism, research value, and future outlook of graphene repair are also discussed at length. Graphene defect repair mainly relies on the spontaneous movement of C atoms or heteroatoms to the pore defects under the condition of applied energy. The repair degree and mechanism of graphene repair are also different according to different preparations. The current research on graphene defect repair is still in its infancy, and it is believed that the problem of defect evolution will be explained in more depth in the future.

Histological observation on acellular nerve grafts co-cultured with Schwann cells for repairing defects of the sciatic nerve

BACKGROUND： Animal experiments and clinical studies about tissue engineering method applied to repair nerve injury mainly focus on seeking ideal artificial nerve grafts, nerve conduit and seed cells. Autologous nerve, allogeneic nerve and xenogeneic nerve are used to bridge nerve defects, it is one of the methods to promote the repair of nerve injury by culturing and growing Schwann cells, which can secrete various neurotrophic factor activities, in the grafts. OBJECTIVE ： To observe the effect of acellular nerve grafts co-cultured with Schwann cells in repairing defects of sciatic nerve. DESIGN： An observational comparative study.SETTING： Tissue Engineering Laboratory of China Medical University.MATERIALS： The experiment was carried out in the Tissue Engineering Laboratory of China Medical University between April 2004 and April 2005. Forty neonatal Sprague-Dawley rats of 5-8 days （either males or females） and 24 male Wistar rats of 180-220 g were provided by the experimental animal center of China Medical University. METHODS： ① Culture of Schwann cells： The bilateral sciatic nerves and branchial plexus were isolated from the 40 neonatal SD rats. The sciatic nerves were enzymatically digested with collagenase and dispase, isolatd, purified and cultured with the method of speed-difference adhersion, and identified with the SABC immunohistochemical method. ② Model establishment： In vitro Schwann cells were microinjected into 10-mm long acellular nerve grafts repairing a surgically created gap in the rat sciatic nerve. According to the different grafted methods, the animals were randomly divided into three groups： autografts （n=8）, acellular nerve grafts （n=8）, or acellular nerve grafts with Schwann cells （n=8）. ③ The regenerated nerve fiber number and average diameter of myeline sheath after culture were statistically anlayzed. MAIN OUTCOME MEASURES： ① The regenerated nerve ultrastructure, total number and density of myelinated nerve fibers, and the thickness of myeline sheath were observed under electron microscope. ② The images were processed with the Mias-1000 imaging analytical system to calculate the number of myelinated nerve fibers, and the thickness of myeline sheath. RESULTS： All the 24 Wistar rats were involved in the analysis of results. ① Results observed under transmission electron microscope： The regenerated myelinated nerve fibers in the group of acellular nerve grafts with Schwann cells were more even than those in the group of acellular nerve grafts, the number of myelinated nerve fibers and thickness of myelin sheath were close to those in the allografts group （P 〉 0.05）, but significantly different from those in the group of acellular nerve grafts （P 〈 0.05）. ② Results observed under scanning electron microscope： A great amount of Schwann cells with two polars were observed in the group of grafts with Schwann cells, the feature of cultured Schwann cells showed shoulder by shoulder, head to head. ③ The number of myelinated nerve fibers and thickness of myelin sheath analyzed by Mias-1000 imaging system in the group of acellular nerve grafts with Schwann cells were close to those in the autografts group （P 〉 0.05）, but significantly different from those in the group of acellular nerve grafts （P 〈 0.05）.CONCLUSION： Host axonal regeneration is significantly increased after implant of acellular nerve grafts. Acellular nerve grafts with Schwann cells offers a novel approach for repairing the gap of nerve defect.

Repair of oral mandibular defects with rib composite flap pedicled with internal thoracic

Objective To study feasibility and value of repair of oral mandibular defects with rib composite flap pedicled with internal thoracic vessels in basic level hospitals. Methods The clinical materials in 13 cases uith mandibular defects which were repaired with rib compos-

Biventricular repair for endocardial cushion defects with double outlet right ventricle

Objective-Double outlet right ventricle,which often associated with total anomalous pulmonary venous connection and complete endocardial cushion defects,has been considered a risk factor for biventricular repair procedure. To reviewed cases treated by biventricular repair for endocardial cushion defects with double outlet right ventricle. Methods From July to November of 2009,6

Repair of infectious scalp defects with titanium mesh exposure by scalp rotation flap

Objective To explore the application of scalp rotation flap in reconstruction of infectious scalp defect with titanium mesh exposure. Methods Twelve patients were treated in this group including 4 males and 8 female. S The defective size ranged from 2. 0 cm × 5. 0 cm to 0.

The influence of yttrium and manganese additions on the degradation and biocompatibility of magnesium-zinc-based alloys:In vitro and in vivo studies

The repair and regeneration of bone defects are highly challenging orthopedic problems.Recently,Mg-based implants have gained popularity due to their unique biodegradation and elastic modulus similar to that of human bone.The aim of our study is to develop a magnesium alloy with a controllable degradation that can closely match bone tissue to help injuries heal in vivo and avoid cytotoxicity caused by a sudden increase in ion concentration.In this study,we prepared and modified Mg-3Zn,Mg-3Zn-1Y,and Mg-2Zn-1Mn by hot extrusion,and used Mg-2.5Y-2.5Nd was as a control.We then investigated the effect of additions of Y and Mn on alloys'properties.Our results show that Mn and Y can improve not only compression strength but also corrosion resistance.The alloy Mg-2Zn-1Mn demonstrated good cytocompatibility in vitro,and for this reason we selected it for implantation in vivo.The degraded Mg-2Zn-1Mn implanted a bone defect area did not cause obvious rejection and inflammatory reaction,and the degradation products left no signs of damage to the heart,liver,kidney,or brain.Furthermore,we find that Mg-2Zn-1Mn can promote an osteoinductive response in vivo and the formation of bone regeneration.

Expression of Transforming Growth Factor β_(1) in Mesenchymal Stem Cells: Potential Utility in Molecular Tissue Engineering for Osteochondral Repair

The feasibility of using gene therapy to treat full-thickness articular cartilage defects was investigated with respect to the transfection and expression of exogenous transforming growth factor(TGF)-β_(1)genes in bone marrow-derived mesenchymal stem cells(MSCs)in vitro.The full-length rat TGF-β_(1)cDNA was transfected to MSCs mediated by lipofectamine and then selected with G418,a synthetic neomycin analog.The transient and stable expression of TGF-β_(1)by MSCs was detected by using immunohistochemical staining.The lipofectamine-mediated gene therapy efficiently transfected MSCs in vitro with the TGF-β_(1)gene causing a marked up-regulation in TGF-β_(1)expression as compared with the vector-transfected control groups,and the increased expression persisted for at least 4 weeks after selected with G418.It was suggested that bone marrow-derived MSCs were susceptible to in vitro lipofectamine mediated TGF-β_(1)gene transfer and that transgene expression persisted for at least 4 weeks.Having successfully combined the existing techniques of tissue engineering with the novel possibilities offered by modern gene transfer technology,an innovative concept,i.e.molecular tissue engineering,are put forward for the first time.As a new branch of tissue engineering,it represents both a new area and an important trend in research.Using this technique,we have a new powerful tool with which:(1)to modify the functional biology of articular tissue repair along defined pathways of growth and differentiation and(2)to affect a better repair of full-thickness articular cartilage defects that occur as a result of injury and osteoarthritis.

Biological and artificial nerve conduit for repairing peripheral nerve defect

OBJECTIVE： Recently, with the development of biological and artificial materials, the experimental and clinical studies on application of this new material-type nerve conduit for treatment of peripheral nerve defect have become the hotspot topics for professorial physicians. DATA SOURCES ： Using the terms ＂nerve conduits, peripheral nerve, nerve regeneration and nerve transplantation＂ in English, we searched Pubmed database, which was published during January 2000 to June 2006, for the literatures related to repairing peripheral nerve defect with various materials. At the same time, we also searched Chinese Technical Scientific Periodical Database at the same time period by inputting ＂ peripheral nerve defect, nerve repair, nerve regeneration and nerve graft＂ in Chinese. STUDY SELECTION ： The materials were firstly selected, and literatures about study on various materials for repairing peripheral nerve defect and their full texts were also searched. Inclusive criteria： nerve conduits related animal experiments and clinical studies. Exclusive criteria： review or repetitive studies. DATA EXTRACTION： Seventy-nine relevant literatures were collected and 30 of them met inclusive criteria and were cited. DATA SYNTHESIS ： Peripheral nerve defect, a commonly seen problem in clinic, is difficult to be solved. Autogenous nerve grafting is still the gold standard for repairing peripheral nerve defect, but because of its application limitation and possible complications, people studied nerve conduits to repair nerve defect. Nerve conduits consist of biological and artificial materials. CONCLUSION： There have been numerous reports about animal experimental and clinical studies of various nerve conduits, but nerve conduit, which is more ideal than autogenous nerve grafting, needs further clinical observation and investigation.

Repair of facial skin defect with a skin flap of SMAS pedicle

To report a method of repair facial skin defects with a skin flap of SMAS pedicle.Methods According to the size of defect of skin,design a skin flap with SMAS pedicle for repair of defect.Results The method has been successfully applied for skin defects of eyelid and lip in 14 cases with satisfied results.The area of the largest flap was 5 cm×3 cm.Conclusion Repairing facial defects such as eyelid skin defect or lip skin defect with skin flap of SMAS pedicle is a very good method.The flap has a good blood supporting and satisfactory color and flexibility.5 refs,6 figs.

Lower rotating point nutrient vessels of sural nerve flap with distant pedicled repairing soft tissue defect of foot and ankle

To explore lower rotating potint nutrient vessels of sural nerve flap with distant pedicled repairing the soft tissue defect of foot and ankle.Methods Lay a foundation of anatomic studying from february 2003 to March 2004,using lower rotating point nutrient vessels of sural nerve flap with distant pedicled repairing the soft tissue defect of foot and ankle in 11 cases.Cause of injuring:traffic accident 7 cases,crushing 1 case,saw injury 1 case,skin cancer 1 case,chronic ulcer 1 case.Areas:foot heel 6 cases,shank lower section 2 cases,heel tendon 2 cases,the distant back of the foot 1 case.Using the flap axis point was 1～3 cm above the pin of the external heel,average 2 cm.The scope of the flap was 6.0 cm×8.0 cm～12.0 cm～18.0 cm.Results All sural nerve flaps were alive.Of them,2 cases have distant part necrosis,accompanying with subcutaneous tissue,1 case heels after change dressings,another heels after skin grafting.All case can walk as usual,the flap was wear-resisting and keenly feel.Conclusion Lower rotating point nutrient vessels of sural nerve flap,donner area was fine,available area was large,skin in the pink,easy grafting,without main blood vessel damage,survival rate high,it is a good donner area in repairing around heel,foot and shank lower section.7 refs,1 tab.

Remote control of the recruitment and capture of endogenous stem cells by ultrasound for in situ repair of bone defects

Stem cell-based tissue engineering has provided a promising platform for repairing of bone defects.However,the use of exogenous bone marrow mesenchymal stem cells(BMSCs)still faces many challenges such as limited sources and potential risks.It is important to develop new approach to effectively recruit endogenous BMSCs and capture them for in situ bone regeneration.Here,we designed an acoustically responsive scaffold(ARS)and embedded it into SDF-1/BMP-2 loaded hydrogel to obtain biomimetic hydrogel scaffold complexes(BSC).The SDF-1/BMP-2 cytokines can be released on demand from the BSC implanted into the defected bone via pulsed ultrasound(p-US)irradiation at optimized acoustic parameters,recruiting the endogenous BMSCs to the bone defected or BSC site.Accompanied by the daily p-US irradiation for 14 days,the alginate hydrogel was degraded,resulting in the exposure of ARS to these recruited host stem cells.Then another set of sinusoidal continuous wave ultrasound(s-US)irradiation was applied to excite the ARS intrinsic resonance,forming highly localized acoustic field around its surface and generating enhanced acoustic trapping force,by which these recruited endogenous stem cells would be captured on the scaffold,greatly promoting them to adhesively grow for in situ bone tissue regeneration.Our study provides a novel and effective strategy for in situ bone defect repairing through acoustically manipulating endogenous BMSCs.

Tumor recurrence after pathological complete response in locally advanced gastric cancer after neoadjuvant therapy:Two case reports

BACKGROUND The pathological complete response(ypCR)rate following neoadjuvant chemotherapy for advanced gastric cancer remains low and lacks a universally accepted treatment protocol.Immunotherapy has achieved breakthrough progress.CASE SUMMARY We report two female patients with gastric cancer defined as clinical stage cT4N1-2M0.Detection of mismatch repair protein showed mismatch repair function defect,and perioperative treatment with programmed death protein 1 inhibitor combined with S-1+oxaliplatin achieved ypCR.Surprisingly,the patients underwent clinical observation after surgery but developed different degrees of metastasis at~6 mo after surgery.CONCLUSION PD-1 inhibitor combined with chemotherapy provides a more strategic choice for comprehensive perioperative treatment of gastric cancer.

Evaluation on the corrosion resistance, antibacterial property and osteogenic activity of biodegradable Mg-Ca and Mg-Ca-Zn-Ag alloys

The rapid degradation of magnesium(Mg)-based implants in physiological environment limits its clinical applications, and alloying treatment is an effective way to regulate the degradation rate of Mg-based materials. In the present study, three Mg alloys, including Mg-0.8Ca(denoted as ZQ), Mg-0.8Ca-5Zn-1.5Ag(denoted as ZQ71) and Mg-0.8Ca-5Zn-2.5Ag(denoted as ZQ63), were fabricated by alloying with calcium(Ca), zinc(Zn) and silver(Ag). The results obtained from electrochemical corrosion tests and in vitro degradation evaluation demonstrated that the three Mg alloys exhibited distinct corrosion resistance, and ZQ71 exhibited the lowest degradation rate in vitro among them. After addition of Zn and Ag, the antibacterial potential of Mg alloys was also enhanced. The in vitro cell experiments showed that all the three Mg alloys had good biocompatibility. After implantation in a rat femoral defect, ZQ71 showed significantly higher osteogenic activity and bone substitution rate than ZQ63 and ZQ, due to its higher corrosion resistance as well as the stimulatory effects of the released metallic ions. In addition, the average daily degradation rate of each Mg alloy in vivo was significantly higher than that in vitro, as could be due to the implantation site located in the highly vascularized trabecular region. Importantly, the correlations between the in vitro and in vivo degradation parameters of the Mg alloys were systematically analyzed to find out the potential predictors of the in vivo degradation performance of the materials. The current work not only evaluated the clinical potential of the three biodegradable Mg alloys as bone grafts but also provided a feasible approach for predicting the in vivo degradation behavior of biodegradable materials.

Molecular Tissue Engineering: Applications for Modulation of Mesenchymal Stem Cells Proliferation by Transforming Growth Factor β_1 Gene Transfer

The effect of transforming growth factor β 1 (TGF β 1 ) gene transfection on the proliferation of bone marrow derived mesenchymal stem cells (MSC S ) and the mechanism was investigated to provide basis for accelerating articular cartilage repairing using molecular tissue engineering technology. TGF β 1 gene at different doses was transduced into the rat bone marrow derived MSCs to examine the effects of TGF β 1 gene transfection on MSCs DNA synthesis, cell cycle kinetics and the expression of proliferating cell nuclear antigen (PCNA). The results showed that 3 μl lipofectamine mediated 1 μg TGF β 1 gene transfection could effectively promote the proliferation of MSCs best; Under this condition (DNA/Lipofectamine=1μg/3μl), flow cytometry and immunohistochemical analyses revealed a significant increase in the 3 H incorporation, DNA content in S phase and the expression of PCNA. Transfection of gene encoding TGF β 1 could induce the cells at G0/G1 phase to S1 phase, modulate the replication of DNA through the enhancement of the PCNA expression, increase the content of DNA at S1 phase and promote the proliferation of MSCs. This new molecular tissue engineering approach could be of potential benefit to enhance the repair of damaged articular cartilage, especially those caused by degenerative joint diseases.

Graphene film for thermal management:A review

Thermal conductivity and thermal dissipation are of great importance for modern electronics due to the increased transistor density and operation frequency of contemporary integrated circuits.Due to its exceptionally high thermal conductivity,graphene has drawn considerable interests worldwide for heat spreading and dissipation.However,maintaining high thermal conductivity in graphene laminates(the basic technological unit)is a significant technological challenge.Aiming at highly thermal conductive graphene films(GFs),this prospective review outlines the most recent progress in the production of GFs originated from graphene oxide due to its great convenience in film processing.Additionally,we also consider such issues as film assembly,defect repair and mechanical compression during the post-treatment.We also discuss the thermal conductivity in in-plane and through-plane direction and mechanical properties of GFs.Further,the current typical applications of GFs are presented in thermal management.Finally,perspectives are given for future work on GFs for thermal management.

The Clinical Application of Human Bone Matrix Gelatin

This paper reports the results of 24 cases of bone defect resulting from bone tumor or tumor condition excision, and of posterior spinal fusion, treated by human bone matrix gelatin. The success rate of bone defect repair and spinal fusion is 91. 67 %. The results suggest that human bone matrix gelatin has. excellent osteoinductive effect and is ideal substitute for bone autografts.

Hippo-YAP/TAZ signaling in osteogenesis and macrophage polarization:Therapeutic implications in bone defect repair

Bone defects caused by diseases or surgery are a common clinical problem.Researchers are devoted to finding biological mechanisms that accelerate bone defect repair,which is a complex and continuous process controlled by many factors.As members of transcriptional costimulatory molecules,Yes-associated protein(YAP)and transcriptional co-activator with PDZ-binding motif(TAZ)play an important regulatory role in osteogenesis,and they affect cell function by regulating the expression of osteogenic genes in osteogenesis-related cells.Macrophages are an important group of cells whose function is regulated by YAP/TAZ.Currently,the relationship between YAP/TAZ and macrophage polarization has attracted increasing attention.In bone tissue,YAP/TAZ can realize diverse osteogenic regulation by mediating macrophage polarization.Macrophages polarize into M1 and M2 phenotypes under different stimuli.M1 macrophages dominate the inflammatory response by releasing a number of inflammatory mediators in the early phase of bone defect repair,while massive aggregation of M2 macrophages is beneficial for inflammation resolution and tissue repair,as they secrete many anti-inflammatory and osteogenesis-related cytokines.The mechanism of YAP/TAZ-mediated macrophage polarization during osteogenesis warrants further study and it is likely to be a promising strategy for bone defect repair.In this article,we review the effect of Hippo-YAP/TAZ signaling and macrophage polarization on bone defect repair,and highlight the regulation of macrophage polarization by YAP/TAZ.

Continuously released Zn^(2+)in 3D-printed PLGA/β-TCP/Zn scaffolds for bone defect repair by improving osteoinductive and anti-inflammatory properties

Long-term nonunion of bone defects has always been a major problem in orthopedic treatment.Artificial bone graft materials such as Poly(lactic-co-glycolic acid)/β-tricalcium phosphate(PLGA/β-TCP)scaffolds are expected to solve this problem due to their suitable degradation rate and good osteoconductivity.However,insufficient mechanical properties,lack of osteoinductivity and infections after implanted limit its large-scale clinical application.Hence,we proposed a novel bone repair bioscaffold by adding zinc submicron particles to PLGA/β-TCP using low temperature rapid prototyping 3D printing technology.We first screened the scaffolds with 1 wt%Zn that had good biocompatibility and could stably release a safe dose of zinc ions within 16 weeks to ensure long-term non-toxicity.As designed,the scaffold had a multi-level porous structure of biomimetic cancellous bone,and the Young’s modulus(63.41±1.89 MPa)and compressive strength(2.887±0.025 MPa)of the scaffold were close to those of cancellous bone.In addition,after a series of in vitro and in vivo experiments,the scaffolds proved to have no adverse effects on the viability of BMSCs and promoted their adhesion and osteogenic differentiation,as well as exhibiting higher osteogenic and anti-inflammatory properties than PLGA/β-TCP scaffold without zinc particles.We also found that this osteogenic and anti-inflammatory effect might be related to Wnt/β-catenin,P38 MAPK and NFkB pathways.This study lay a foundation for the follow-up study of bone regeneration mechanism of Zn-containing biomaterials.We envision that this scaffold may become a new strategy for clinical treatment of bone defects.