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Background: Current clinical approaches to regenerate temporomandibular joint (TMJ) articulating cartilage defects only treat the symptoms (i.e. pain and dysfunction) and do not seek to restore joint integrity for long‐term relief. Therefore, we investigated a novel self‐assembling tissue‐engineered cartilage to overcome this significant clinical issue for TMJ regenerative purposes. Objectives: Examine the maturation of dynamic self‐regenerating cartilage (dSRC) using auricular chondrocytes and evaluate a novel combinatorial approach with fractional laser treatment and dSRC implantation for TMJ cartilage repair. Materials and Methods: A suspension of 107 freshly harvested rabbit ear chondrocytes was cultured under a continuous reciprocating motion to form the dSRC. After 2, 4 and 8 weeks of culture, dSRC samples were stained with H&E, Safranin‐O and Toluidine Blue. Immunohistochemistry (IHC) was performed for collagens type I and II. Channels (300–500 μm diameter and 1.2–1.5 mm depth) were created in six freshly harvested condyles using a fractional Erbium laser. Two groups were tested: dSRC in a laser‐ablated lesion (experimental) and an empty laser‐ablated channel (control). TMJ condyles were cultured for up to 8 weeks and analysed as described above. Results: H&E staining showed a high cell density in dSRC compared to native cartilage. All dSRC groups demonstrated intense Safranin‐O staining, indicating high glycosaminoglycan (GAG) production and intense Toluidine Blue staining showed high proteoglycan content. IHC confirmed that dSRC consisted predominantly of collagen type II. The experimental group showed improved cartilage repair at both time points compared to the empty channels. Conclusion: dSRC viability and successful matrix formation were demonstrated in vitro. The combination of fractional laser ablation and dSRC implantation enhanced cartilage repair. [ABSTRACT FROM AUTHOR]

Background: In the last decade, tissue‐engineering strategies for regenerating the temporomandibular joint (TMJ) have been investigated. This may be a promising strategy for the minimally invasive restoration of joint integrity. Objectives: To evaluate whether dental pulp stem cells (DPSCs) loaded in a light‐occured hydrogel made of gelatin methacryloyl (GelMA) enhance the regeneration of osteochondral defects in the rabbit TMJ. Materials and Methods: Defects were filled with GelMA alone (control group; n = 4) or filled with GelMA loaded with rabbit DPSCs (experimental group; n = 4), In one group, the TMJ capsule was opened without creating a defect (sham group; n = 2). The following micro‐CT parameters were analysed: bone volume to total volume ratio (BV/TV%) and bone mineral density (BMD). Histological evaluation was performed to assess cartilage regeneration features. A semi‐quantitative scoring system was also used to evaluate the defects. Results: All groups had no statistical difference regarding the micro‐CT parameters. The highest mean healing score was found for the experimental group. After 4 weeks, there were no signs of hydrogel in either group or no signs of inflammation in the adjacent tissues. The tissue formed in the defect was dense fibrous connective tissue. Conclusion: Adding DPSCs to GelMA did not provide a regenerative enhancement in TMJ osteochondral defects. This resulted in similar micro‐CT parameters after 4 weeks of healing, with improved signs of subchondral bone regeneration but no cartilage regeneration. [ABSTRACT FROM AUTHOR]

Periprosthetic joint infections occur in about 2% of patients who undergo primary total joint arthroplasty, a procedure performed over 1 million times in the United States. The gold standard of treatment is a two‐stage revision. This study aimed to establish a two‐stage procedure in a preclinical small animal model (rat) to test and compare the efficacy of an antibiotic‐eluting material in managing infection. Joint replacement was simulated by transchondylarly implanting a polyethylene (PE) plug into the distal femur and a titanium screw in the proximal tibia. Methicillin‐sensitive Staphylococcus aureus (MSSA) 108 CFU/mL was injected into the tibial canal and the joint space before wound closure. The control groups were killed on postoperative day (POD) 18 (n = 12) and on POD 42 (n = 4) to assess both early and later‐stage outcomes in the control group. The test group underwent revision surgery on POD 18 for treatment using gentamicin‐eluting polyethylene (GPE, n = 4) and was observed until POD 42 to evaluate the efficacy of treatment. Our results showed that the bone loss for the treatment group receiving GPE was significantly less than that of the control (p < 0.05), which was supported by the histology images and an AI‐tool assisted infection rate evaluation. Gait metrics duty factor imbalance and hindlimb temporal symmetry were significantly different between the treatment and control groups on Day 42. This animal model was feasible for evaluating treatments for peri‐prosthetic joint infections (PJI) with a revision surgery and specifically that revision surgery and local antibiotic treatment largely hindered the peri‐prosthetic bone loss. Statement of clinical significance: This revision model of peri‐prosthetic infection has the potential of comparatively evaluating prophylaxis and treatment strategies and devices. Antibiotic‐eluting UHMWPE is devised as at tool in treating PJI while providing weight bearing and joint space preservation. [ABSTRACT FROM AUTHOR]

The volume of a submarine landslide is likely to be amplified by shear band propagation along a basal surface or spreading failure extension in the sliding layer. Although the mechanism of translational submarine landslides has been understood using the interpretation of shear band propagation, assessment of the limits of failure extension, either through shear band propagation or retrogressive spreading, remains a challenge due to the diversity of post failure mechanisms. The paper aims to explore all post failure possibilities and quantify failure initiation and extension accordingly, focusing on the upslope conditions. The different failure mechanisms are explored with the aid of the large deformation finite element modeling. Original criteria for scarp position, shear band length at slab failure, retrogression conditions and ultimate spreading limits are proposed, following the process zone approach considering force equilibrium of the sliding mass. Simplified analytical predictions are shown to agree well with the numerical observations. The findings and criteria presented in the study are expected to help assess the ultimate scale of upslope failure in submarine landslides, which is important in determining geohazard zonation of submarine landslides. Plain Language Summary: Submarine landslides are often huge compared to onshore counterparts, but why and how huge? Answering these questions will increase our understanding of submarine landslide evolution and help to assess risks of submarine landslide recurrence. For example, the Storegga Slide offshore Norway, which occurred ∼8,200 years ago, covered an area as large as UK and triggered tsunami waves seriously impacting nearby islands. A large submarine landslide might be initiated from localized failure within an embedded weak layer, followed by failure propagation along the weak layer and extensive slab failure in the overlying sliding layer. These two post‐failure phenomena may greatly increase the scale of submarine landslides. Here we simulate submarine landslides in different conditions and explore all possible upslope post‐failure mechanisms, using a large deformation numerical modeling method. Based on the observed mechanisms, we develop a new model and original criteria to predict the scarp position and failure extension limit of submarine landslides. Altogether, findings here are expected to help assess the ultimate scale of submarine landslides, which is important in determining geohazard zonation of submarine landslides. Key Points: We explore and quantify all upslope failure possibilities of submarine landslides through numerical modeling and theoretical analysesWe establish a framework for assessing failure initiation, covering different failure mechanismsWe propose simple predictions for scarp position and retrogression limit, which allows rapid assessment of scale of submarine landslides [ABSTRACT FROM AUTHOR]

Summary: Soil–water interaction is a pivotal process in many underwater geohazards such as underwater landslides where soil sediments gradually evolve into turbidity currents after interactions with ambient water. Due to the large deformations, multiphase interactions and phase changes this involves, investigations from numerical modelling of the transition process have been limited so far. This study explores a simple numerical replication of such soil–water mixing with respect to changes in average strength using smoothed particle hydrodynamics (SPH). A uniform viscoplastic model is used for both the solid‐like and fluid‐like SPH particles. The proposed numerical solution scheme is verified by single‐phase dam break tests and multiphase simple shear tests. SPH combinations of solid‐like and fluid‐like particles can replicate the clay–water mixture as long as the liquidity index of the solid‐like particles is larger than unity. The proposed numerical scheme is shown to capture key features of an underwater landslide such as hydroplaning, water entrainment and wave generation and thus shows promise as a tool to simulate the whole process of subaquatic geohazards involving solid–fluid transition during mass transport. [ABSTRACT FROM AUTHOR]

The majority of periprosthetic joint infections occur shortly after primary joint replacement (<3 months) and require the removal of all implant components for the treatment period (~4 months). A clinically relevant animal model of periprosthetic infection should, therefore, establish an infection with implant components in place. Here, we describe a joint replacement model in the rat with ultrahigh molecular weight polyethylene (UHMWPE) and titanium components inoculated at the time of surgery by methicillin‐sensitive Staphylococcus aureus (S. aureus), which is one of the main causative microorganisms of periprosthetic joint infections. We monitored the animals for 4 weeks by measuring gait, weight‐bearing symmetry, von Frey testing, and micro‐CT as our primary endpoint analyses. We also assessed the infection ex vivo using colony counts on the implant surfaces and histology of the surrounding tissues. The results confirmed the presence of a local infection for 4 weeks with osteolysis, loosening of the implants, and clinical infection indicators such as redness, swelling, and increased temperature. The utility of specific gait analysis parameters, especially temporal symmetry, hindlimb duty factor imbalance, and phase dispersion was identified in this model for assessing the longitudinal progression of the infection, and these metrics correlated with weight‐bearing asymmetry. We propose to use this model to study the efficacy of using different local delivery regimens of antimicrobials on addressing periprosthetic joint infections. Statement of clinical significance: We have established a preclinical joint surgery model, in which postoperative recovery can be monitored over a multi‐week course by assessing gait, weight‐bearing, and allodynia. This model can be used to study the efficacy of different combinations of implant materials and medication regimens. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 38:1101‐1112, 2020 [ABSTRACT FROM AUTHOR]

Quantitative assessment of the risk of submarine landslides is an essential part of the design process for offshore oil and gas developments in deep water, beyond the continental shelf. Landslides may be triggered by a reduction in shear strength of subsea sediments over a given zone, caused for example by seismic activity. Simple criteria are then needed to identify critical conditions whereby the zone of weakness could grow catastrophically to cause a landslide. A number of such criteria have been developed over the last decade, based either on ideas drawn from fracture mechanics, or considering the equilibrium of the initial weakened zone and adjacent process zones of gradually softening material. Accounting for the history of the weak zone initiation is critical for derivation of reliable propagation criteria, in particular considering dynamic effects arising from accumulating kinetic energy of the failing material, which will allow the failure to propagate from a smaller initial zone of weakened sediments. Criteria are developed here for planar conditions, taking full account of such dynamic effects, which are shown to be capable of reducing the critical length of the softened zone by 20% or more compared with criteria based on static conditions. A numerical approach is used to solve the governing dynamic equations for the sliding material, the results from which justify assumptions that allow analytical criteria to be developed for the case where the initial softening occurs instantaneously. The effect of more gradual softening is also explored. Copyright © 2016 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Background The objective of this study was to investigate the humoral immune response to xenogeneic antigens administered during the fetal state utilizing a baboon-to-pig model. Methods Nine fetuses from an alpha-1,3-galactosyltransferase gene knockout (GalT- KO) MGH-miniature swine sow underwent transuterine ultrasound-guided intraportal injection of T-cell depleted baboon bone marrow (B- BM) at mid-gestation. Two juvenile GalT-KO swine undergoing direct B- BM intraportal injection were used as controls. Results Postnatal humoral tolerance was induced in the long-term surviving piglets as demonstrated by the absence of any antibody response to baboon donor cells. In addition, a second intraportal B- BM administration at 2.5 months post-birth led to no antibody formation despite re-exposure to xenogeneic antigens. This B-cell unresponsiveness was abrogated only when the animal was exposed subcutaneously to third-party xenogeneic and allogeneic antigens, suggesting that the previously achieved humoral non-responsiveness was donor specific. In comparison, the two juvenile GalT-KO control swine demonstrated increasing anti-baboon IgM and IgG levels following intraportal injection. Conclusions In summary, xenogeneic B-cell tolerance was induced through in utero intraportal exposure to donor cells and this tolerance persisted following postnatal rechallenge with donor B- BM, but was lost on exposure to third-party antigen, possibly as a result of cross-reactive antibody formation. [ABSTRACT FROM AUTHOR]

SUMMARY The paper presents analytical solutions for the evolution of excess pore pressures in the vicinity of a shear band in a rate-dependent, strain-softening permeable soil, with the aim to explore, both qualitatively and quantitatively, the potential variation of failure shear stress in the shear band. The solutions encompass both dissipation of a pre-existing pore pressure regime within the main soil domain, and the effects of generation of additional pore pressure within the shear band itself. The simplified analytical solutions were checked by numerical inversion of exact solutions in Laplace transform space, confirming their high accuracy. The solutions show that it is possible for the failure shear stress to rise initially because of short-term dissipation of the pre-existing excess pore pressure at a faster rate than generation of new excess pore pressure within the shear band. This apparent strain hardening in a strain-softening soil can be misleading in that it can temporarily slow down the sliding mass and create a false sense of stabilization of the slope. It can also result in additional temporary shear resistance for sliding foundations or pipelines on the seabed. Copyright © 2015 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

The objective of this study was to assess the ability of tissue engineered cartilage to adhere to and integrate with porous polyethylene (PPE) in vivo and to evaluate the biomechanical integrity of the bond formed at the interface. Porcine auricular, articular, and costal chondrocytes were suspended in fibrin gel polymer and placed between discs of PPE to form tri-layer constructs. Controls consisted of fibroblasts suspended in gel or gel alone between the discs. Constructs were implanted into nude mice for 6, 12, and 18 weeks. Upon harvest, specimens were evaluated for neocartilage formation and integration into the PPE, using histological, dimensional (mass, thickness, diameter), and biomechanical (adhesion strength, interfacial stiffness, failure energy and failure strain) analyses. Neotissue was formed in all experimental constructs, consisting mostly of neocartilage integrating with discs of PPE. Control samples contained only fibrous tissue. Biomechanical analyses demonstrated that adhesion strength, interfacial stiffness, and failure energy were all significantly higher in the chondrocyte-seeded samples than in fibroblast-seeded controls, with the exception of costal constructs at 12 weeks, which were not significantly greater than controls. In general, failure strains did not vary between groups. In conclusion, porous polyethylene supported the growth of neocartilage that formed mechanically functional bonds with the PPE. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 103B: 983-991, 2015. [ABSTRACT FROM AUTHOR]

This study investigated a dual crosslinking paradigm, consisting of (a) photocrosslinking with Rose Bengal (RB) and green light followed by (b) chemical crosslinking with 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC), and N-hydroxysuccinimide (NHS) to enhance collagen gel stiffness. In group 1, 50 μL collagen constructs of 2% (w/v) type I collagen containing 10 μ M RB were allowed to gel spontaneously at 37°C. In group 2, the spontaneous gels were exposed to green light (532 nm). In group 3, the photochemically crosslinked gels were subsequently treated with a 1-h exposure to 33 m M EDC/6 m M NHS. Samples ( n = 18) were subjected to 0.08% (w/v) collagenase digestion, and the storage modulus of samples was measured by rheometry. Viability of encapsulated chondrocytes was measured by live/dead assay. Chondrocytes were ≥95% viable in all constructs at 10 days in vitro. Resistance to collagenase digestion increased as; spontaneous gels (2 h) < photochemical gels (3-4 h) < dual crosslinked gels (>24 h). The storage modulus of dual-crosslinked constructs was increased 5-fold over both photocrosslinked and spontaneous gels. As the dual crosslinking paradigm did not reduce encapsulated chondrocyte viability, these crosslinked collagen hydrogels could be a useful tool for the practical delivery of encapsulated chondrocytes to articular defects. © 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 1332-1338, 2015. [ABSTRACT FROM AUTHOR]

An approximate solution for the effects of high strain rates, and gradual strength degradation, on the penetration resistance of penetrometers can be obtained by combining the strain-path method with the classical upper bound theorem. The stream path calculations require the integration of the material constitutive equation along the streamlines. Unless the geometry is simple so that the integration can be evaluated analytically, numerical procedures are required to backtrack streamlines. The strain at any location is calculated by finding the streamline that passes through the given point and integrating the strain rate along that streamline from its inlet boundary. Thus, the calculations can be complicated, and errors can be accumulated during the calculation procedure. This paper presents an efficient approach for evaluating cumulative strains around penetrometers without the need to backtrack individual streamlines. In this approach, the strain components are treated as field variables. The global solution is obtained using the streamline upwind Petrov-Galerkin method. The new method together with an Eulerian-based finite element formulation was used to study the cone penetration test and evaluate the effect of strain softening on the cone resistance. Copyright © 2014 John Wiley & Sons, Ltd. [ABSTRACT FROM AUTHOR]

Healing articular cartilage defects remains a significant clinical challenge because of its limited capacity for self-repair. While delivery of autologous chondrocytes to cartilage defects has received growing interest, combining cell-based therapies with growth factor delivery that can locally signal cells and promote their function is often advantageous. We have previously shown that PEG thiol-ene hydrogels permit covalent attachment of growth factors. However, it is not well known if embedded chondrocytes respond to tethered signals over a long period. Here, chondrocytes were encapsulated in PEG hydrogels functionalized with transforming growth factor-beta 1 (TGF-β1) with the goal of increasing proliferation and matrix production. Tethered TGF-β1 was found to be distributed homogenously throughout the gel, and its bioactivity was confirmed with a TGF-β1 responsive reporter cell line. Relative to solubly delivered TGF-β1, chondrocytes presented with immobilized TGF-β1 showed significantly increased DNA content, and GAG and collagen production over 28 days, while maintaining markers of articular cartilage. These results indicate the potential of thiol-ene chemistry to covalently conjugate TGF-β1 to PEG to locally influence chondrocyte function over 4 weeks. Scaffolds with other or multiple tethered growth factors may prove broadly useful in the design of chondrocyte delivery vehicles for cartilage tissue engineering applications. © 2014 The Authors. Journal of Biomedical Materials Research Part A Published by Wiley Periodicals, Inc.: 102A: 4464-4472, 2014. [ABSTRACT FROM AUTHOR]

A cell-based engineered construct can be used for healing of intractable meniscal lesions. Our aims were to assess the culture conditions (static versus dynamic oscillation) and the healing capacity of the chondrocyte-seeded flexible implants in a heterotopic mouse model. Swine articular chondrocytes were labeled with PKH 26 or DiI dye and seeded onto a flexible PLGA scaffold using dynamic oscillating conditions for 24 h. Half of cell-seeded scaffolds were cultured in the same dynamic conditions, while the remaining scaffolds were cultured statically. After 7 days, scaffolds were placed between swine meniscal discs and were implanted subcutaneously in nude mice for 6 weeks. Additional constructs for assessing in vivo cell tracking were implanted for 12 weeks. Live/dead assays demonstrated labeled chondrocytes attached throughout the scaffold in both culture conditions. DNA measurements showed no significant difference between the culture conditions. A continuous fibro-cartilaginous healing tissue was observed between meniscal discs in all 12 dynamically cultured constructs and 9 of 11 statically cultured ones. There was no evidence of meniscal healing using acellular scaffold as well as in meniscal constructs lacking an implant. Both PKH 26- and DiI-labeled cells were identified along the healing interface. We conclude the chondrocyte-seeded flexible PLGA implants induce healing of meniscal discs in nude mice. Culture conditions after seeding have no apparent effects on healing. © 2011 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 99A: 102-108, 2011. [ABSTRACT FROM AUTHOR]

Although previous studies have established alginate as a three-dimensional scaffold for chondrogenic differentiation of mesenchymal stem cells (MSCs), little is known about the cytotoxic effects of the polymerizing and chelating reagents used in the alginate recovered cellular method. Swine MSCs (sMSC) were suspended in the polymerizing agent, CaCl2, and viability was assessed using a trypan blue exclusion assay at intervals over 2 h. MSCs were also suspended in two different chelating agents, 55 m M sodium citrate and 50 m M EDTA, and viability was calculated. Finally, sMSCs and human MSCs were encapsulated and cultured in vitro. The sMSC were collected at day 4 and the cells were recovered by chelation. Encapsulated hMSCs were cultured with TGFβ3 and IGF-1 and assayed by qRT-PCR for collagen types I and II and sox9 with encapsulated human dermal fibroblasts and chondrocytes as controls recovered on days 0, 7, and 14. Only 53% of sMSCs were viable after 10 min in CaCl2, the standard polymerization period, whereas 94% of encapsulated sMSCs in polymerized alginate were alive at 15 days. After 20 min in chelating agents, sodium citrate and EDTA, only 46% and 17% of the cells, were viable, respectively. The alginate recovered sMSCs yielded 12% survival. Human MSCs upregulated cartilage-specific collagen type II over the 14-day culture. Collagen I remained unchanged in the hMSCs. Alginate is a suitable agent for chondrodifferentiation of MSCs and can be dissolved by chelation, but the agents involved in hydrogel polymerization and cell recovery should be altered to improve MSC survival. © 2010 Wiley Periodicals, Inc. J Biomed Mater Res Part A:, 2010. [ABSTRACT FROM AUTHOR]