Repair Model Research Articles

Biocomposite Anchors Have Greater Yield Load and Energy Compared With All-Suture Anchors in an In Vitro Ovine Infraspinatus Tendon Repair Model

PurposeTo compare tensile fatigue and strength measures of biocomposite and all-suture anchors in an ovine humerus-infraspinatus tendon model of rotator cuff repair. MethodsInfraspinatus tendons on adult ovine humeri were sharply transected at the insertion. One of each pair was randomly assigned for fixation with two biocomposite or all-suture anchors. Constructs were tested with 200 cycles of 20-70 N tensile load and gap formation was measured at the incised tendon end every 50 cycles. They were subsequently tested to failure. Outcome measures including fatigue stiffness, hysteresis, creep and gap formation, and tensile stiffness, and yield and failure displacement, load, and energy were compared between anchors. ResultsBiocomposite anchors had higher yield load (134.1 ± 6.5 N, p<.01) and energy (228.6 ± 85.7 J, p<.03) than all-suture anchors (104.7 ± 6.5 N, 169.8 ± 85.7 J). Fatigue properties were not different between anchors, but stiffness and gap formation increased and hysteresis and creep decreased significantly with increasing cycle number. ConclusionsWhile the yield displacement of both anchors was within the range of clinical failure, the tensile yield load and energy of ovine infraspinatus tendons secured to the humerus with two single-loaded all-suture anchors in a single row were significantly lower than those secured with two biocomposite anchors in the same configuration. Clinical RelevanceIt is important to understand the biomechanical properties for selecting anchors for rotator cuff repair. A direct comparison of fatigue testing followed by failure strength of infraspinatus tendon fixation with all-suture and biocomposite anchors could help guide anchor selection and post-operative mobility recommendations.

Human nonunion tissues display differential gene expression in comparison to physiological fracture callus

The healing of bone fractures can become aberrant and lead to nonunions which in turn have a negative impact on patient health. Understanding why a bone fails to normally heal will enable us to make a positive impact in a patient's life. While we have a wealth of molecular data on rodent models of fracture repair, it is not the same with humans. As such, there is still a lack of information regarding the molecular differences between normal physiological repair and nonunions. This study was designed to address this gap in our molecular knowledge of the human repair process by comparing differentially expressed genes (DEGs) between physiological fracture callus and two different nonunion types, hypertrophic (HNU) and oligotrophic (ONU). RNA sequencing data revealed over ∼18,000 genes in each sample. Using the physiological callus as the control and the nonunion samples as the experimental groups, bioinformatic analyses identified 67 and 81 statistically significant DEGs for HNU and ONU, respectively. Out of the 67 DEGs for the HNU, 34 and 33 were up and down-regulated, respectively. Similarly, out of the 81 DEGs for the ONU, 48 and 33 were up and down-regulated, respectively. Additionally, we also identified common genes between the two nonunion samples; 8 (10.8 %) upregulated and 12 (22.2 %) downregulated. We further identified many biological processes, with several statistically significant ones. Some of these were related to muscle and were common between the two nonunion samples. This study represents the first comprehensive attempt to understand the global molecular events occurring in human nonunion biology. With further research, we can perhaps decipher new molecular pathways involved in aberrant healing of human bone fractures that can be therapeutically targeted.

Analisa Antrian di SPBU Pondok Ungu menggunakan Software Promodel

Queuing is a daily routine experienced by almost everyone. Every activity, such as refueling at gas stations, has a queuing process. The purpose of this research is to reduce the average customer waiting time in the system, reduce the average idle time on each server, and reduce the length of the queue in the system. Because at the gas station there are long queues, it is necessary to improve the queuing system. In addition, Promodel software is used to simulate queuing models at gas stations. This research is qualitative and quantitative in nature. Based on the results of the study it was concluded that. In the initial model entity there were only 40 people while in the new model there were 48 people. In the initial model, the average entity location is 0.33, while the new model is 0.65. But the repair model has an average time spent on the system a little longer, which is 0.60.

Interposition of acellular amniotic membrane at the tendon to bone interface would be better for healing than overlaying above the tendon to bone junction in the repair of rotator cuff injury

PurposeThe retear rate of rotator cuff (RC) after surgery is high, and the rapid and functional enthesis regeneration remains a challenge. Whether acellular amniotic membrane (AAM) helps to promote the healing of tendon to bone and which treatment is better are both unclear. The study aims to investigate the effect of AAM on the healing of RC and the best treatment for RC repair. MethodsThirty-three Sprague Dawley rats underwent RC transection and repair using microsurgical techniques and were randomly divided into the suturing repair only (SRO) group (n = 11), the AAM overlaying (AOL) group (n = 11), and the AAM interposition (AIP) group (n = 11), respectively. Rats were sacrificed at 4 weeks, then examined by subsequent micro-CT, and evaluated by histologic and biomechanical tests. The statistical analyses of one-way ANOVA or Kruskal-Wallis test were performed using with SPSS 23.0. A p < 0.05 was considered a significant difference. ResultsAAM being intervened between tendon and bone (AIP group) or overlaid over tendon to bone junction (AOL group) in a rat model, promoted enthesis regeneration, increased new bone and cartilage generation, and improved collagen arrangement and biomechanical properties in comparison with suturing repair only (SRO group) (AOL vs. SRO, p < 0.001, p = 0.004, p = 0.003; AIP vs. SRO, p < 0.001, p < 0.001, p < 0.001). Compared with the AOL group, the AIP group had better results in micro-CT evaluation, histological score, and biomechanical testing (p = 0 0.039, p = 0.011, p = 0.003, respectively). ConclusionIn the RC repair model, AAM enhanced regeneration of the tendon to bone junction. This regeneration was more effective when the AAM was intervened at the tendon to bone interface than overlaid above the tendon to bone junction.

Gal - T Knockout Porcine Nerve Xenografts Support Axonal Regeneration in a Rodent Sciatic Nerve Model.

Nerve xenografts harvested from transgenic α1,3-galactosyltransferase knockout (GalT-KO) pigs lack the epitope responsible for hyperacute rejection in pig-to-primate transplants. It is unknown whether these cold preserved nerve grafts support axonal regeneration in another species during and after immunosuppression. In this study, we compare outcomes between autografts and cold preserved xenografts in a rat sciatic model of nerve gap repair. Fifty male Lewis rats had a 1 cm sciatic nerve defect repaired using either: autograft and suture (n=10); 1-week or 4-week cold preserved xenograft and suture (n=10 per group); 1-week or 4-week cold preserved xenograft and photochemical tissue bonding using a human amnion wrap (PTB/HAM) (n=10 per group). Rats with xenografts were given tacrolimus until 4 months post-operatively. At 4 and 7 months, rats were euthanized and nerve sections harvested. Monthly sciatic functional index (SFI) scores were calculated. All groups showed increases in SFI scores by 4 and 7 months. The autograft suture group had the highest axon density at 4 and 7 months. The largest decrease in axon density from 4 to 7 months was in the 1-week cold preserved PTB/HAM group. The only significant difference between group SFI scores occurred at 5 months, when both 1-week cold preserved groups had significantly lower scores than the 4-week cold preserved suture group. Our results in the rat sciatic model suggest that GalT-KO nerve xenografts may be viable alternatives to autografts and demonstrate the need for further studies of long-gap repair and comparison with acellular nerve allografts. This proof-of-concept study in the rat sciatic model demonstrates that cold preserved GalT-KO porcine xenografts support axonal regeneration, as well as axonal viability following immunosuppression withdrawal. These results further suggest a role for both cold preservation and photochemical tissue bonding in modulating the immunological response at the nerve repair site.

Tuhu Automotive Service: The Growth Path of the Leader in the after-sales Market

After its establishment in 2011, Tuhu Automotive Service led the Chinese automotive market to open up a new business track of standardized after-sales market. After the O2O+ auto parts B2C model of maintenance and repair, the B2C+B2B model was derived with the change of market, which broadened the user channel and quickly expanded its popularity with the enterprise integrity and affordable service, occupying most of the Chinese after-sales market. The success of the after-sales market has made many large-scale capitals also eye on this increasingly large business track. Tuhu Automotive Service is still trying to explore to cope with the challenges from the capital magnates.

Acellular porcine Achilles tendon patch encapsulating tendon-derived stem cells for rotator cuff repair in a rabbit model

Currently, the predominant method for repairing rotator cuff involves surgical suture techniques, but the failure rate remains notably high. Failure of the rotator cuff insertion to provide adequate biomechanics during early healing is considered a major cause of failure. Addressing this problem, biological augmentation emerges as a promising strategy for enhancing the biomechanical properties during early stages. Tendon-derived stem cells (TDSCs), which facilitate the differentiation of repair-supportive cells, hold the potential to improve the efficacy of patch application. The study aims to assess the behavior of TDSCs in acellular porcine Achilles tendon (APAT) patches and to explore the capacity of the APAT patch encapsulating TDSCs in promoting both tendon-to-bone healing and biomechanical enhancements in a rabbit rotator cuff repair model. Transmission electron microscopy (TEM) analyses validated the complete cellular clearance of native cells from APAT patches, with uniform distribution of TDSCs. Immunofluorescence staining confirmed successful TDSCs attachment, while population doubling time (PDT) underscored increased TDSCs proliferation on APAT patches. Quantitative polymerase chain reaction (qPCR) demonstrated upregulation of tenocyte and osteocyte related genes in TDSCS cultured within the patches. In the subsequent in vivo experiment, fifty-four rabbits were used to create rotator cuff injury models and randomly assigned to a control group, an APAT patch group, and an APAT patch with TDSCs group. Histological analysis showed that the APAT patch with TDSCs group had significantly enhanced tendon-to-bone healing and a distinctly organized tendon-fibrocartilage-bone structure, as compared to the APAT patch group. In addition, the biomechanical properties of the APAT patch with TDSCs group were significantly improved. In conclusion, APAT patches promote TDSC proliferation and stimulate tenogenic and osteogenic differentiation. APAT patches encapsulating TDSCs have shown considerable potential in promoting tendon-to-bone healing of rotator cuff injuries, indicating that their use in rotator cuff repair surgery is clinically meaningful.

Influence of modelling hypotheses on strength assessment of CFRP stepped repairs

Composite stepped repairs can achieve high strength recovery without the addition of bolts or fasteners to the structure. They are therefore a major issue in the field of aerospace composite structure damage repair. However, there is no standardized method to design this type of repairs. Many analytical, semi-analytical and finite element models were proposed throughout the years to predict the strength of stepped repairs, using various hypotheses and simplifications. The aim of this paper is to investigate the influence of modelling hypotheses on stress distribution and strength prediction of composite stepped repairs. Five simplified stepped joint models using macro-element (ME) modelling and finite element method (FE) are compared to a full 3D FE model of a stepped repaired panel. The influence of step length and adhesive fracture toughness was investigated to determine the field of validity of each model. Among FE models, it was shown that modelling the equivalent joint under 2D generalized plain strain gives a very close strength prediction to the 3D stepped repair model while saving computation time. Simplified macro-element models under bar or beam hypotheses are fairly close to the results of FE modelling, but the deviation between those and FE is sensitive to step length and adhesive fracture toughness.

H3K4me1 recruits DNA repair proteins in plants.

DNA repair proteins can be recruited by their histone reader domains to specific epigenomic features, with consequences on intragenomic mutation rate variation. Here, we investigated H3K4me1-associated hypomutation in plants. We first examined 2 proteins which, in plants, contain Tudor histone reader domains: PRECOCIOUS DISSOCIATION OF SISTERS 5 (PDS5C), involved in homology-directed repair, and MUTS HOMOLOG 6 (MSH6), a mismatch repair protein. The MSH6 Tudor domain of Arabidopsis (Arabidopsis thaliana) binds to H3K4me1 as previously demonstrated for PDS5C, which localizes to H3K4me1-rich gene bodies and essential genes. Mutations revealed by ultradeep sequencing of wild-type and msh6 knockout lines in Arabidopsis show that functional MSH6 is critical for the reduced rate of single-base substitution (SBS) mutations in gene bodies and H3K4me1-rich regions. We explored the breadth of these mechanisms among plants by examining a large rice (Oryza sativa) mutation data set. H3K4me1-associated hypomutation is conserved in rice as are the H3K4me1-binding residues of MSH6 and PDS5C Tudor domains. Recruitment of DNA repair proteins by H3K4me1 in plants reveals convergent, but distinct, epigenome-recruited DNA repair mechanisms from those well described in humans. The emergent model of H3K4me1-recruited repair in plants is consistent with evolutionary theory regarding mutation modifier systems and offers mechanistic insight into intragenomic mutation rate variation in plants.

Fibrin Contributes to an Improvement of an in vitro Wound Repair Model using Fibroblast-populated Collagen Lattices

Incisional acute wounds of the skin are characterized by a rapid biomechanical response by stromal cell contraction that joins the wound lips through the fibrin cloth. In this work, we have performed an in vitro model using Fibroblast-Populated Collagen Lattices (FPCLs) that partially mimic that physiological process. Injured FPCLs under relaxed or stressed conditions were evaluated over time, and cross-sections of the lattices were stained with picrosirius red. Wounds filled with fibrin in relaxed FPCLs were closed earlier than controls, the fibrillar pattern of the collagen lattice was different between the wound and the edges of the lattice. On the other hand, stressed FPCLs did not close wounds, even those filled with fibrin, because the tension generated from the lattice borders maintained high tension towards the wound. Controls or fibrin-treated stressed FPCLs, showed high tension in the wound matrix, characterized by the high packing of collagen observed like yellow-red birefringent fibers when stained by picrosirius red. Despite wounds that remain open, fibrin-treated FPCLs exhibited less wound area than controls. With this work, we have demonstrated that FPCL models can be used to study wound closure, mainly when they are improved with other elements of the wound environment that allow us to analyze the biological process.

Stock Levels and Repair Sourcing in a Periodic Review Exchangeable Item Repair System

Background: Exchangeable item repair systems are inventory systems. A nonfunctional item is exchanged for a functional item and returns to the system after being repaired. In our periodic review setting, repair is performed either in-house or outsourced. When repair is in-house, a repaired item is returned to stock regardless of the repair status of the other items in its order. In contrast, with outsourced repair, the entire order must be repaired for it to return to stock. Methods: We develop formulas for the window fill rate (probability for a customer to be served within a given time window) to measure the system’s performance and compute it for each repair model. The cost of outsourcing is the difference between the number of spares needed to maintain a target performance level when repair is internal and when it is outsourced. Results and Conclusions: In our numerical example, we show that the window fill rate in both models is S-shaped in the number of spares and show how the graph shifts to the right when customer tolerance decreases and order cycle time increases. Further, we show that the cost of outsourcing is increasing with customer tolerance and with the target performance level.

Repair of Inferior Alveolar Nerve in Orthognathic Surgery Simulator (RIANOS): A Novel, Open-Source, Combined 3D Printed, and Ex-Vivo Chicken Sciatic Nerve Training Model

Study Design Face and content validation of a surgical simulation model. Objective Accidental transection of the inferior alveolar nerve (IAN) during bilateral sagittal split osteotomies (BSSO) has a reported incidence of up to 7%, determining important sensory disturbances in patients. Proper repair demands the need of microsurgical anastomosis skills. No previous training models have been described to simulate this. Therefore, we present a validated simulation model for intraoral repair of transected IAN. Methods A CT scan of an orthognathic surgery patient was modified and a 3D model of a mandible with BSSO was printed. Chicken thigh anatomy was reviewed, and 2.5 mm sciatic nerves were dissected and mounted in the model. In order to simulate intraoral work depth, it was put inside a dental phantom or medical glove box. The model was tested by a group of experts (n = 12), simulating a transected IAN repair inside the mouth with both loupes and a double visor surgical training microscope. A survey was conducted to assess Face and Content validity. Results The model was named RIANOS after Repair of Inferior Alveolar Nerve in Orthognathic Surgery Simulator. The printing cost of each model was approximately US$3 and the design file is open-source and available for download. All experts “Strongly Agreed” that the model was useful for training inferior alveolar nerve microsurgical repair and would consider implementing it with their residents. Conclusions We developed a low cost, reproducible, open-source simulator for IAN injury repair training during BSSO. Face and Content validity was achieved through evaluation by a group of experts.

Bending of a lipid membrane edge by annexin A5 trimers

Plasma membrane damage occurs in healthy cells and more frequently in cancer cells where high growth rates and metastasis result in frequent membrane damage. The annexin family of proteins plays a key role in membrane repair. Annexins are recruited at the membrane injury site by Ca+2 and repair the damaged membrane in concert with several other proteins. Annexin A4 (ANXA4) and ANXA5 form trimers at the bilayer surface, and previous simulations show that the trimers induce high local negative membrane curvature on a flat bilayer. The membrane-curvature-inducing property of ANXA5 is presumed to be vital to the membrane repair mechanism. A previously proposed descriptive model hypothesizes that ANXA5-mediated curvature force is utilized at the free edge of the membrane at a wound site to pull the wound edges together, resulting in the formation of a “neck”-shaped structure, which, when combined with a constriction force exerted by ANXA6, leads to membrane repair. The molecular details and mechanisms of repair remain unknown, in part because the membrane edge is a transient structure that is difficult to investigate both experimentally and computationally. For the first time, we investigate the impact of ANXA5 near a membrane edge, which is modeled by a bicelle under periodic boundary conditions. ANXA5 trimers induce local curvature on the membrane leading to global bending of the bicelle. The global curvature depends on the density of annexins on the bicelle, and the curvature increases with the ANXA5 concentration until it reaches a plateau. The simulations suggest that not only do annexins induce local membrane curvature, but they can change the overall shape of a free-standing membrane. We also demonstrate that ANXA5 trimers reduce the rate of phosphatidylserine lipid diffusion from the cytoplasmic to the exoplasmic leaflet along the edge of the bicelle. In this way, membrane-bound annexins can potentially delay the apoptotic signal triggered by the presence of phosphatidylserine lipids in the outer leaflet, thus biding time for repair of the membrane hole. Our findings provide new insights into the role of ANXA5 at the edges of the membrane (the injury site) and support the curvature-constriction model of membrane repair.

Poison Attack and Poison Detection on Deep Source Code Processing Models

In the software engineering (SE) community, deep learning (DL) has recently been applied to many source code processing tasks, achieving state-of-the-art results. Due to the poor interpretability of DL models, their security vulnerabilities require scrutiny. Recently, researchers have identified an emergent security threat to DL models, namely, poison attacks . The attackers aim to inject insidious backdoors into DL models by poisoning the training data with poison samples. The backdoors mean that poisoned models work normally with clean inputs but produce targeted erroneous results with inputs embedded with specific triggers. By using triggers to activate backdoors, attackers can manipulate poisoned models in security-related scenarios (e.g., defect detection) and lead to severe consequences. To verify the vulnerability of deep source code processing models to poison attacks, we present a poison attack approach for source code named CodePoisoner as a strong imaginary enemy. CodePoisoner can produce compilable and functionality-preserving poison samples and effectively attack deep source code processing models by poisoning the training data with poison samples. To defend against poison attacks, we further propose an effective poison detection approach named CodeDetector . CodeDetector can automatically identify poison samples in the training data. We apply CodePoisoner and CodeDetector to six deep source code processing models, including defect detection, clone detection, and code repair models. The results show that ❶ CodePoisoner conducts successful poison attacks with a high attack success rate (average: 98.3%, maximum: 100%). It validates that existing deep source code processing models have a strong vulnerability to poison attacks. ❷ CodeDetector effectively defends against multiple poison attack approaches by detecting (maximum: 100%) poison samples in the training data. We hope this work can help SE researchers and practitioners notice poison attacks and inspire the design of more advanced defense techniques.

Pentamidine-loaded gelatin decreases adhesion formation of flexor tendon

BackgroundPrevention of adhesion formation following flexor tendon repair is essential for restoration of normal finger function. Although many medications have been studied in the experimental setting to prevent adhesions, clinical application is limited due to the complexity of application and delivery in clinical translation. MethodsIn this study, optimal dosages of gelatin and pentamidine were validated by gelatin concentration test. Following cell viability, cell migration, live and dead cell, and cell adhesion assay of the Turkey tenocytes, a model of Turkey tendon repair was established to evaluate the effectiveness of the Pentamidine-Gelatin sheet. ResultsPentamidine carried with gelatin, a Food and drug administration (FDA) approved material for drug delivery, showed good dynamic release, biocompatibility, and degradation. The optimal dose of pentamidine (25ug) was determined in the in vivo study using tenocyte viability, migration, and cell adhesion assays. Further biochemical analyses demonstrated that this positive effect may be due to pentamidine downregulating the Wnt signaling pathway without affecting collagen expression. ConclusionsWe tested a FDA-approved antibiotic, pentamidine, for reducing adhesion formation after flexor tendon repair in both in vitro and in vivo using a novel turkey animal model. Compared with the non-pentamidine treatment group, pentamidine treated turkeys had significantly reduced adhesions and improved digit function after six weeks of tendon healing. The translational potential of this articleThis study for the first time showed that a common clinical drug, pentamidine, has a potential for clinical application to reduce tendon adhesions and improve tendon gliding function without interfering with tendon healing.

Reputation-Damaging Events Over a Long Time Horizon: An Event-System Model of Substantive Reputation Repair

Current models of substantive reputation repair primarily focus on isolated reputation-damaging events (RDEs) and corresponding responses by firms within short time frames. Nevertheless, evidence suggests that firms encounter numerous RDEs over extended periods while only sporadically and intermittently engaging in top-down substantive repair. To investigate this event-response asynchrony, we adopt an event system theory (EST) approach and conduct a qualitative study of a multinational firm. Over a 10-year period, we analyzed 47 RDEs that eventually prompted top management to initiate substantive repair. Our findings reveal that top managers perceive reputation management as a complex system comprising self-correcting subsystems that follow recurring adaptive event cycles. These cycles consist of iterations, transitioning from routine business-as-usual activities managing most RDEs (foreloops) to nonlinear, transformative responses to certain events (backloops). As long as these cycles are deemed effective, top managers refrain from substantive repair, intervening only when they identify a subsystem breakdown. Consequently, our event-system model of substantive reputation repair elucidates event-response asynchrony in two phases: (1) top managers’ confidence in the hierarchy of adaptive event cycles leads them to purposefully avoid most RDEs, and (2) the convergent intersection of three specific event chain patterns gradually establishes a shared narrative among top managers, triggering top-down substantive repair. By employing EST, we not only provide novel insights into how firms manage reputations but also enhance the explanatory power of EST by illuminating event cycle dynamics.

Microparticle deposition induced asymmetric adhesive hydrogel for suture-less gastric trauma treatment

Stomach trauma repair remains a paramount concern in the biomedical field. Despite numerous studies into the creation of gastric hydrogel patches, many exhibit inadequate wet-state adhesion or problematic double-sided adhesion that can inadvertently adhere to surrounding tissues. Consequently, asymmetric adhesive hydrogels are one of the directions for the development of suture-less sealing wound patches for the stomach trauma. However, existing asymmetric patches often entail intricate fabrication processes, challenging their scalability for industrial production. In this study, we propose a novel and universal preparation method for fabricating asymmetric adhesive hydrogel patches for favorable suture-less sealing gastric repair based on the existing high adhesive strength hydrogel patch research. This is followed by a thorough examination of its adhesion qualities using various adhesion tests. MTS assay and AO staining method are used to confirm the cytocompatibility. The bursting test is used to simulate in vitro stomach trauma. Subsequently,a rat gastric trauma repair model is performed to mimic its application in actual surgery, and its excellent repair effect is confirmed by immunohistochemical staining and immunofluorescence staining, which verifies the potential of asymmetric adhesive hydrogel patches prepared by microparticle deposition induced method in biomedical field.

A novel porous titanium with engineered surface for bone defect repair in load-bearing position.

Porous titanium exhibits low elastic modulus and porous structure is thought to be a promising implant in bone defect repair. However, the bioinert and low mechanical strength of porous titanium have limited its clinical application, especially in load-bearing bone defect repair. Our previous study has reported an infiltration casting and acid corrosion (IC-AC) method to fabricate a novel porous titanium (pTi) with 40% porosity and 0.4 mm pore diameter, which exerts mechanical property matching with cortical bone and interconnected channels. In this study, we introduced a nanoporous coating and incorporated an osteogenic element strontium (Sr) on the surface of porous titanium (named as Sr-micro arch oxidation [MAO]) to improve the osteogenic ability of the pTi by MAO. Better biocompatibility of Sr-MAO was verified by cell adhesion experiment and cell counting kit-8 (CCK-8) test. The in vitro osteogenic-related tests such as immunofluorescence staining, alkaline phosphatase staining and real-time polymerase chain reaction (RT-PCR) demonstrated better osteogenic ability of Sr-MAO. Femoral bone defect repair model was employed to evaluate the osseointegration of samples in vivo. Results of micro-CT scanning, sequential fluorochrome labeling and Van Gieson staining suggested that Sr-MAO showed better in vivo osteogenic ability than other groups. Taking results of both in vitro and in vivo experiment together, this study indicated the Sr-MAO porous titanium could be a promising implant load-bearing bone defect.

A biologically inspired repair mechanism for neuronal reconstructions with a focus on human dendrites.

Investigating and modelling the functionality of human neurons remains challenging due to the technical limitations, resulting in scarce and incomplete 3D anatomical reconstructions. Here we used a morphological modelling approach based on optimal wiring to repair the parts of a dendritic morphology that were lost due to incomplete tissue samples. In Drosophila, where dendritic regrowth has been studied experimentally using laser ablation, we found that modelling the regrowth reproduced a bimodal distribution between regeneration of cut branches and invasion by neighbouring branches. Interestingly, our repair model followed growth rules similar to those for the generation of a new dendritic tree. To generalise the repair algorithm from Drosophila to mammalian neurons, we artificially sectioned reconstructed dendrites from mouse and human hippocampal pyramidal cell morphologies, and showed that the regrown dendrites were morphologically similar to the original ones. Furthermore, we were able to restore their electrophysiological functionality, as evidenced by the recovery of their firing behaviour. Importantly, we show that such repairs also apply to other neuron types including hippocampal granule cells and cerebellar Purkinje cells. We then extrapolated the repair to incomplete human CA1 pyramidal neurons, where the anatomical boundaries of the particular brain areas innervated by the neurons in question were known. Interestingly, the repair of incomplete human dendrites helped to simulate the recently observed increased synaptic thresholds for dendritic NMDA spikes in human versus mouse dendrites. To make the repair tool available to the neuroscience community, we have developed an intuitive and simple graphical user interface (GUI), which is available in the TREES toolbox (www.treestoolbox.org).

Viable cartilage allograft outperforms existing treatments for focal knee cartilage defects.

Viable cartilage allograft (VCA) is a cartilage tissue matrix that contains cryopreserved viable allogeneic cartilage fibres. This study aimed to assess safety and benefits in treating focal knee cartilage defects with VCA. We hypothesized that VCA is a safe single-stage procedure in isolated chondral defects. In vitro analysis, in vivo studies and a prospective case series were performed. VCA was evaluated in a goat cartilage repair model. Symptomatic International Cartilage Repair Society grade 3/4A lesions of the femoral condyle or patella were implanted with VCA. International Knee Documentation Committee (IKDC), Knee injury and Osteoarthritis Outcome (KOOS) subscales, Lysholm, Short Form-12, Visual Analog Scale and pain frequency levels were assessed. Radiographic and magnetic resonance imaging (MRI) was performed at regular intervals postoperatively. Data were analysed by statisticians to determine the power and significance of the results. The goat study confirmed that VCA is effective for cartilage repair. Twenty patients were implanted; the mean age was 28.1 (16-56), the mean body mass index (BMI) was 27.9 ± 5.6 and the mean follow-up was 24.1 months (range = 12.0-36.0 months). Lesions were in either the femoral condyle (7) or patella (13). Lesion sizes ranged from 1.5 to 6.0 cm2 (mean = 4.58 cm2 ). Outcome scores improved from preoperative baseline (POB): IKDC (78.2), Lysholm (89.0), KOOS: Pain (95.8), Symptoms (86.3), ADL (87.8), Sports (85.0) and QOL (75.0). MRI imaging demonstrated excellent osteochondral allograft assimilation. Second-look arthroscopy (two patients) demonstrated complete fill and incorporation (Brittberg scores 11/12). Functional scores were maintained at 24 (M): IKDC (86.24 ± 17.2), Lysholm (87.23 ± 15.0), KOOS: Pain (91.72 ± 17.3), Symptoms (84.92 ± 16.1), ADLs (93.80 ± 16.1), Sports (84.45 ± 27.7), QOL (81.30 ± 20.8). VCA is an off-the-shelf, single-stage, conformable allogeneic graft that treats chondral defects with no additional fixation. Preclinical and short-term prospective clinical studies show that VCA can safely treat chondral defects with potential advantages to existing options. Level IV study.