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Surgical reconstruction of the torn ACL is performed to restore native contact mechanics. Drawbacks to traditional ACL repair techniques motivate the development of a tissue engineered ACL scaffold. Our group has developed a hierarchical electrospun polycaprolactone (PCL) scaffold that consists of rolled nanofiber bundles attached at each end with solvent-case blocks of PCL. The goal of this study was to compare ovine cadaver tibiofemoral contact mechanics after ACL reconstruction with the electrospun scaffold to a clinically applicable ACL reconstruction with a soft tissue graft and the ACL transected condition (ACLX). In the ACLX group and after ACL reconstruction with either the electrospun scaffold or soft tissue graft, pressure sensors were inserted under the menisci. Loads up to 890 N were applied at various flexion angles. The scaffold performed the best at restoring contact mechanics in the medial hemijoint to that of the native ACL. The scaffold was good at maintaining a medial-lateral balance of pressures as in the native joint whereas the ACLX shifted pressure off the lateral and on to the medial hemijoint. While the ACL scaffold didn't restore mechanics to that of the native condition, it improved contact mechanics compared to the standard graft replacement and ACLX condition.

Focal defects in articular cartilage are unable to self-repair and, if left untreated, are a leading risk factor for osteoarthritis. This study examined cartilage degeneration surrounding a defect and then assessed whether infilling the defect prevents degeneration. We created a focal chondral defect in porcine osteochondral explants and cultured them ex vivo with and without dynamic compressive loading to decouple the role of loading. When compared to a defect in a porcine knee four weeks post-injury, this model captured loss in sulfated glycosaminoglycans (sGAGs) along the defect's edge that was observed in vivo, but this loss was not load dependent. Loading, however, reduced the indentation modulus of the surrounding cartilage. After infilling with in situ polymerized hydrogels that were soft (100 kPa) or stiff (1 MPa) and which produced swelling pressures of 13 and 310 kPa, respectively, sGAG loss was reduced. This reduction correlated with increased hydrogel stiffness and swelling pressure, but was not affected by loading. This ex vivo model recapitulates sGAG loss surrounding a defect and, when infilled with a mechanically supportive hydrogel, degeneration is minimized.

Due to the complex and dynamic nature of osteoarthritis (OA) and post-traumatic osteoarthritis (PTOA), animal models have been used to investigate the progression and pathogenesis of the disease. Researchers have used different experimental models to study OA and PTOA. With an emphasis on the knee joint, this review will compare and contrast the existing body of knowledge from anterior cruciate ligament transection models, meniscectomy models, combination models, as well as impact models in large animals to see how tissues respond to these different approaches to induce experimental OA and PTOA. The tissues discussed will include articular cartilage and the meniscus, with a focus on morphological, mechanical and histological assessments. The goal of this review is to demonstrate the progressive nature of OA by indicating the strong correlation between progressive tissue degeneration, change of mechanical properties, and loss of biochemical integrity and to highlight key differences between the most commonly used experimental animal models.

Summary Objective Quantitative, micrometer length scale assessment of human articular cartilage is essential to enable progress toward new functional tissue engineering approaches, including utilization of emerging 3D bioprinting technologies, and for improved computational modeling of the osteochondral unit. Thus the objective of this study was to characterize the structural organization, material properties, and chemical composition of human skeletally mature articular cartilage with respect to depth and defined morphological features: normal to the articulating surface, parallel to the split-line, and transverse to the split-line. Method Three samples from the lateral femoral condyles of 4 healthy adult donors (55–61 years old) were evaluated via histology, second harmonic generation, microindentation, and Raman spectroscopy. All metrics were evaluated as a function of depth and direction relative to the split-line. Results All donors presented with intact and healthy tissue. Collagen fiber orientation varied significantly between testing directions and with increasing depth from the articular surface. Both compressive and tensile modulus increased significantly with depth and differed across the middle and deep zones and depended on orthogonal direction relative to the split-line. Similarly, matrix components varied with both depth and direction, where chondroitin sulfate steadily increased with depth while collagen prevalence was highest in the surface layer. Conclusions Microscale measurements of human articular cartilage demonstrate that properties are both depth-dependent and orthotropic and depend on the underlying tissue structure and composition. These findings improve upon existing knowledge establishing more accurate measurements, with greater degree of depth and spatial specificity, as inputs for tissue engineering and computational modeling.

Designed by Dr. Sethi, the Jaipur Foot prosthesis is ideally suited for amputees in developing countries as it utilizes locally sourced, biodegradable, inexpensive materials and is focused on affordability and functionality. To date, however, no data have been reported on the material properties of the foot components.The goal of this work was to evaluate mechanical properties of the Jaipur Foot components to guide foot design and manufacturing and reduce weight.Experimental.Mechanical testing was conducted on two types of woods (ardu and cheed), microcellular rubber, tire cord, cushion compound, tread compound, and skin-colored rubber. Each material was subjected to testing in either tension or compression based on its location and function in the foot. Samples were tested before and after vulcanization. Two-sample t-tests were used to assess statistical differences.Cheed compressed perpendicular to the grain had a significantly higher modulus of elasticity than ardu ( p 0.05); however, cheed had a higher density. Vulcanization significantly increased the modulus of skin-colored rubber, cushion compound, and tread compound ( p 0.05) and decreased the moduli of both microcellular rubber and tire cord ( p 0.05).The material property results from this study provide information for computer modeling to assess material construction on overall foot mechanics for design optimization. Ardu wood was ideal based on the desire to reduce weight, and the tire cord properties serve well to hold the foot together. Clinical relevance With new knowledge on the material properties of the components of the Jaipur Foot, future design modifications and standardized fabrication can be realized, making the Jaipur Foot more available on a global scale.

Synthesis of hydrogel networks capable of accurately replicating the biomechanical demands of musculoskeletal soft tissues continues to present a formidable materials science challenge. Current systems are hampered by combinations of limited moduli at biomechanically relevant strains, inefficiencies driven by undesirable hysteresis and permanent fatigue, and recovery dynamics too slow to accommodate rapid cycling prominent in most biomechanical loading profiles. Here, we report on a novel paradigm in hydrogel design based on prefabrication of an efficient nanoscale network architecture using the melt-state self-assembly of amphiphilic block copolymers. Rigorous characterization and mechanical testing reveal that swelling of these preformed networks produces hydrogels with physiologically relevant moduli and water compositions, negligible hysteresis, subsecond elastic recovery rates, and unprecedented resistance to fatigue over hundreds of thousands of compression cycles. Furthermore, by relying only on simple thermoplastic processing to form these nanostructured networks, the synthetic complexities common to most solution-based hydrogel fabrication strategies are completely avoided.

Successful 3D scaffold designs for musculoskeletal tissue engineering necessitate full consideration of the form and function of the tissues of interest. When designing structures for engineering cartilage and osteochondral tissues, one must reconcile the need to develop a mechanically robust system that maintains the health of cells embedded in the scaffold. In this work, we present an approach that decouples the mechanical and biochemical needs and allows for the independent development of the structural and cellular niches in a scaffold. Using the highly tuned capabilities of digital light processing-based stereolithography, structures with complex architectures are achieved over a range of effective porosities and moduli. The 3D printed structure is infilled with mesenchymal stem cells and soft biomimetic hydrogels, which are specifically formulated with extracellular matrix analogs and tethered growth factors to provide selected biochemical cues for the guided differentiation towards chondrogenesis and osteogenesis. We demonstrate the ability to utilize these structures to (a) infill a focal chondral defect and mitigate macroscopic and cellular level changes in the cartilage surrounding the defect, and (b) support the development of a stratified multi-tissue scaffold for osteochondral tissue engineering.

Understanding how human meniscal tissue responds to loading regimes mimetic of daily life as well as how it compares to larger animal models is critical in the development of a functionally accurate synthetic surrogate. Seven human and eight ovine cadaveric meniscal specimens were regionally sectioned into cylinders 5 mm in diameter and 3 mm thick along with 10 polystyrene-b-polyethylene oxide block copolymer-based thermoplastic elastomer (TPE) hydrogels. Samples were compressed to 12% strain at 1 Hz for 5000 cycles, unloaded for 24 h, and then retested. No differences were found within each group between test one and test two. Human and ovine tissue exhibited no regional dependency (p

The objective of this study was to compare longitudinal results from two models of combined anterior cruciate ligament (ACL) and meniscal injury. A modified ACL transection (mACLT) model and a traumatic impact (ACLF) model were used to create an ACL rupture and acute meniscal damage in a Flemish Giant animal model. The animals were euthanized at time points of 4, 8, or 12 weeks. The menisci were assessed for equilibrium and instantaneous compressive modulus, as well as glycosaminoglycan (GAG) coverage. The articular cartilage was mechanically assessed for thickness, matrix modulus, fiber modulus, and permeability. Articular cartilage GAG coverage, fissuring, tidemark integrity, and subchondral bone thickness were measured. Both models resulted in damage indicative of osteoarthritis, including decreased meniscal mechanics and GAG coverage, increased permeability and fissuring of articular cartilage, and decreased GAG coverage. The mACLT model had an early and lasting effect on the menisci mechanics and GAG coverage, while cartilage damage was not significantly affected until 12 weeks. The ACLF model resulted in an earlier change of articular cartilage GAG coverage and fissuring in both the 8 and 12 week groups. The menisci were only significantly affected at the 12 week time point in the ACLF model. We concluded the progression of post traumatic osteoarthritis was dependent on injury modality: a point to be considered in future investigations. © 2016 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:486-495, 2017.

Post-traumatic osteoarthritis (PTOA) develops as a result of traumatic loading that causes tears of the soft tissues in the knee. A modified transection model, where the anterior cruciate ligament (ACL) and both menisci were transected, was used on skeletally mature Flemish Giant rabbits. Gross morphological assessments, elastic moduli, and glycosaminoglycan (GAG) coverage of the menisci were determined to quantify the amount of tissue damage 12 weeks post injury. This study is one of the first to monitor meniscal changes after inducing combined meniscal and ACL transections. A decrease in elastic moduli as well as a decrease in GAG coverage was seen.

Traumatic injury to the knee leads to the development of posttraumatic osteoarthritis. The objective of this study was to characterize the effects of a single intra-articular injection of a non-ionic surfactant, Poloxamer 188 (P188), in preservation of meniscal tissue following trauma through maintenance of meniscal glycosaminoglycan (GAG) content and mechanical properties. Flemish Giant rabbits were subjected to a closed knee joint, traumatic compressive impact with the joint constrained to prevent anterior tibial translation. The contralateral limb served as an un-impacted control. Six animals (treated) received an injection of P188 in phosphate buffered saline (PBS) post trauma, and another six animals (sham) received a single injection of PBS to the impacted limb. Histological analyses for GAG was determined 6 weeks post trauma, and functional outcomes were assessed using stress relaxation micro-indentation. The impacted limbs of the sham group demonstrated a significant decrease in meniscal GAG coverage compared to non-impacted limbs (p < 0.05). GAG coverage of the impacted P188 treated limbs was not significantly different than contralateral non-impacted limbs in all regions except the medial anterior (p < 0.05). No significant changes were documented in mechanics for either the sham or treated groups compared to their respective control limbs. This suggests that a single intra-articular injection of P188 shows promise in prevention of trauma induced GAG loss.

Healthy menisci function within the joint to prevent the underlying articular cartilage from excessive loads. Understanding how mechanical properties of menisci change with degeneration can drive future therapeutic studies to prevent this degeneration. Thus, the goal of this study was to characterize both compressive and tensile moduli of human menisci with varying degrees of gross damage due to osteoarthritis (OA). Twenty four paired menisci were collected from total knee joint replacement patients and the menisci were graded on a scale from 0-4 according to level of gross meniscal degeneration with 0=normal and 4=full tissue maceration. Each meniscus was then sectioned into anterior and posterior regions and subjected to indentation relaxation tests. Samples were sliced into 1mm thick strips, made into dumbbells using a custom punch, and pulled to failure. Significant decreases in instantaneous compressive modulus were seen in the lateral posterior region between grades 0 and 1 (36% decrease) and in the medial anterior regions between grades 1 and 2 (67% decrease) and 1 and 3 (72% decrease). Changes in equilibrium modulus where seen in the lateral anterior region between grades 1 and 2 (35% decrease), lateral posterior region between grades 0-2 (41% decrease), and medial anterior regions between grades 1 and 2 (59% decrease), 1 and 3 (67% decrease), 2 and 4 (54% decrease), and 3 and 4 (42% decrease). No significant changes were observed in tensile modulus across all regions and degenerative grades. The results of this study demonstrate the compressive moduli are affected even in early stages of gross degeneration, and continue to decrease with increased deterioration. However, osteoarthritic menisci retain a tensile modulus similar to that of previously reported healthy menisci. This study highlights progressive changes in meniscal mechanical compressive integrity as level of gross tissue degradation increases, and thus, early interventions should focus on restoring or preserving compressive integrity.

Hydrogels are a class of synthetic biomaterials composed of a polymer network that swells with water and as such they have both an elastic and viscous component making them ideal for soft tissue applications. This study characterizes the compressive, tensile, and shear properties of a thermoplastic elastomer (TPE) hydrogel and compares the results to published literature values for soft tissues such as articular cartilage, the knee meniscus, and intervertebral disc components. The results show the TPE hydrogel material is viscoelastic, strain rate dependent, has similar surface and bulk properties, displays minimal damping under dynamic load, and has tension-compression asymmetry. When compared to other soft tissues it has a comparable equilibrium compressive modulus of approximately 0.5MPa and shear modulus of 0.2MPa. With a tensile modulus of only 0.2MPa though, the TPE hydrogel is inferior in tension to most collagen based soft tissues. Additional steps may be necessary to reinforce the hydrogel system and increase tensile modulus depending on the desired soft tissue application. It can be concluded that this material could be a viable option for soft tissue replacements.

The purpose of this study was to examine effects of usage and demographics on damage to the Jaipur Foot prosthesis as well as the epidemiology and etiology of amputations performed at Santokba Durlabjhi Memorial Hospital (SDMH) in Jaipur, India.Total time spent standing, total time spent wearing and total distance walked were compared against severity and location of damage to the prosthesis. Time between initial fitting and follow-up visit for damaged prosthetic was also considered in this analysis. A novel damage severity scale based on prosthesis functionality is presented along with a damage location legend.Patients from 10 different states and two territories throughout India were included in the study. No main effects were found to be statistically significant in predicting severity or location of damage. Only the interaction between a patient's total time spent standing and their total time spent wearing the prosthesis as well as the interaction between a patient's total time spent standing and total distance walked was significant in predicting location of damage to the Jaipur Foot (p = .0327, p = .0278, respectively).The lack of significant usage factor effect on damage severity or location could support previous findings that lack standardization in materials and manufacturing processes, which is the major drawback of the Jaipur Foot. Implications for Rehabilitation The Jaipur Foot is a safe, reliable and stable product as no abrupt breakage or sudden falls causing injury to the patient were noted. Hence, it is a safe rehabilitation device for lost limbs. The population can squat and sit cross-legged while wearing the prosthetic foot and it does not affect damage severity or location of damage, allowing for these activities to be performed while rehabilitating. The manufacturing of the foot needs to be standardized to improve life of foot. Total time spent standing, total time spent wearing and total distance walked were not predictive of severity or location of damage to the prosthesis, hence providing patient guidelines for activity during rehabilitation.

Understanding how human meniscal tissue responds to loading regimes mimetic of daily life as well as how it compares to larger animal models is critical in the development of a functionally accurate synthetic surrogate. Seven human and eight ovine cadaveric meniscal specimens were regionally sectioned into cylinders 5 mm in diameter and 3 mm thick along with 10 polystyrene-b-polyethylene oxide block copolymer-based thermoplastic elastomer (TPE) hydrogels. Samples were compressed to 12% strain at 1 Hz for 5000 cycles, unloaded for 24 h, and then retested. No differences were found within each group between test one and test two. Human and ovine tissue exhibited no regional dependency (p 0.05). Human samples relaxed quicker than ovine tissue or the TPE hydrogel with modulus values at cycle 50 not significantly different from cycle 5000. Ovine menisci were found to be similar to human menisci in relaxation profile but had significantly higher modulus values (3.44 MPa instantaneous and 0.61 MPa after 5000 cycles compared with 1.97 and 0.11 MPa found for human tissue) and significantly different power law fit coefficients. The TPE hydrogel had an initial modulus of 0.58 MPa and experienced less than a 20% total relaxation over the 5000. Significant differences in the magnitude of compressive modulus between human and ovine menisci were observed, however the relaxation profiles were similar. Although statistically different than the native tissues, modulus values of the TPE hydrogel material were similar to those of the human and ovine menisci, making it a material worth further investigation for use as a synthetic replacement. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 2722-2728, 2017.

Summary Objective The objective of this study was to monitor the progression of joint damage in two animal models of knee joint trauma using two non-invasive, clinically available imaging modalities. Methods A 3-T clinical magnet and micro-computed tomography (μCT) was used to document changes immediately following injury (acute) and post-injury (chronic) at time points of 4, 8, or 12 weeks. Joint damage was recorded at dissection and compared to the chronic magnetic resonance imaging (MRI) record. Fifteen Flemish Giant rabbits were subjected to a single tibiofemoral compressive impact (ACLF), and 18 underwent a combination of anterior cruciate ligament (ACL) and meniscal transection (mACLT). Results All ACLF animals experienced ACL rupture, and 13 also experienced acute meniscal damage. All ACLF and mACLT animals showed meniscal and articular cartilage damages at dissection. Meniscal damage was documented as early as 4 weeks and worsened in 87% of the ACLF animals and 71% of the mACLT animals. Acute cartilage damage also developed further and increased in occurrence with time in both models. A progressive decrease in bone quantity and quality was documented in both models. The MRI data closely aligned with dissection notes suggesting this clinical tool may be a non-invasive method for documenting joint damage in lapine models of knee joint trauma. Conclusions The study investigates the acute to chronic progression of meniscal and cartilage damage at various time points, and chronic changes to the underlying bone in two models of posttraumatic osteoarthritis (PTOA), and highlights the dependency of the model on the location, type, and progression of damage over time.

Inverse finite element (FE) analysis is an effective method to predict material behavior, evaluate mechanical properties, and study differences in biological tissue function. The meniscus plays a key role in load distribution within the knee joint and meniscal degradation is commonly associated with the onset of osteoarthritis. In the current study, a novel transversely isotropic hyper-poro-viscoelastic constitutive formulation was incorporated in a FE model to evaluate changes in meniscal material properties following tibiofemoral joint impact. A non-linear optimization scheme was used to fit the model output to indentation relaxation experimental data. This study is the first to investigate rate of relaxation in healthy versus impacted menisci. Stiffness was found to be decreased (p=0.003), while the rate of tissue relaxation increased (p=0.010) at twelve weeks post impact. Total amount of relaxation, however, did not change in the impacted tissue (p=0.513).

The objective of this study was to induce anterior cruciate ligament (ACL) and meniscal damage, via a single tibiofemoral compressive impact, in order to document articular cartilage and meniscal changes post impact. Tibiofemoral joints of Flemish Giant rabbits were subjected to a single blunt impact that ruptured the ACL and produced acute meniscal damage. Animals were allowed unrestricted cage activity for 12 weeks before euthanasia. India ink analysis of the articular cartilage revealed higher degrees of surface damage on the impacted tibias (p=0.018) and femurs (p

Post-traumatic osteoarthritis (PTOA) develops as a result of traumatic loading that causes tears of the soft tissues in the knee. A modified transection model, where the anterior cruciate ligament (ACL) and both menisci were transected, was used on skeletally mature Flemish Giant rabbits. Gross morphological assessments, elastic moduli, and glycosaminoglycan (GAG) coverage of the menisci were determined to quantify the amount of tissue damage 12 weeks post injury. This study is one of the first to monitor meniscal changes after inducing combined meniscal and ACL transections. A decrease in elastic moduli as well as a decrease in GAG coverage was seen.

Genetics, obesity, and mechanical loading conditions such as trauma can increase the risk of development of OA. Posttraumatic OA, or OA resulting from trauma, is thought to account for 12% of all patients exhibiting OA.1 A number of injuries can lead to posttraumatic OA, but it is most commonly seen following sports injuries where anterior cruciate ligament (ACL) and meniscal injuries have occurred.2Copyright © 2013 by ASME