We investigated whether preoperative perturbation training would help anterior cruciate ligament (ACL) deficient individuals who complain of knee instability (“non-copers”) regain quadriceps strength and walk normally after ACL reconstruction. Nineteen non-copers with acute ACL injury were randomly assigned into a perturbation group (PERT) or a strengthening group (STR). The PERT group received specialized neuromuscular training and progressive quadriceps strength training, whereas the STR group received progressive quadriceps strength training only. We compared quadriceps strength indexes and knee excursions during the mid-stance phase of gait preoperatively to data collected 6 months after ACL reconstruction. Analyses of Variance with repeated measures (time/limb) were conducted to compare quadriceps strength index values over time (time × group) and differences in knee excursions in limbs between groups over time (limb × time × group). If significance was found, post hoc analyses were performed using paired and independent t-tests. Quadriceps strength indexes before intervention (Pert: 87.2%; Str: 75.8%) improved 6 months after ACL reconstruction in both groups (Pert: 97.1%; Str: 94.4%). Non-copers who received perturbation training preoperatively had no differences in knee excursions between their limbs 6 months after ACL reconstruction (p = 0.14), whereas those who received just strength training continued to have smaller knee excursions during the mid-stance phase of gait (p = 0.007). Non-copers strength and knee excursions were more symmetrical 6 months postoperatively in the group that received perturbation training and progressive quadriceps strength training than the group who received strength training alone.

Loss of experimental animals due to tendon repair failure results in the need for additional animals to complete the study. We designed a relief proximal to the flexor digitorum profundus (FDP) tendon repair site to serve as a “safety incision” to prevent repair site ruptures and maximize safety incision-to-suture strength. The FDP tendons were dissected in 24 canine forepaws. The 2nd and 5th tendons were lacerated at the proximal interphalangeal joint level and sutured using a modified Kessler technique and peripheral running suture. Tendon width was measured where the FDP tendon separates into each individual digit and a safety incision, equal to the 2nd and 5th tendon widths, was performed 3, 4, or 5 mm (Groups 1, 2, and 3) proximal to the separation. The tendons were pulled at a rate of 1 mm/s until either the “safety incision” ruptured or the repair failed. There was no gap formation at the repair site in Groups 1 and 2. However, all Group 3 tendons failed by repair site rupture with the safety incision intact. An adequate safety incision to protect repair gap and rupture and maintain tendon tension for the FDP animal model should be about 4 mm from where the FDP tendon separates.

Post-arthroplasty infections are a devastating problem in orthopaedic surgery. While acute infections can be treated with a single stage washout and liner exchange, chronic infections lead to multiple reoperations, prolonged antibiotic courses, extended disability and worse clinical outcomes. Unlike previous mouse models that studied an acute infection, this work aimed to develop a model of a chronic post-arthroplasty infection. To achieve this, a stainless steel implant in the knee joints of mice was inoculated with a bioluminescent S. aureus strain (1×102–1×104 CFUs) and in vivo imaging was used to monitor the bacterial burden for 42 days. Four different S. aureus stains were compared in which the bioluminescent construct was integrated in an antibiotic selection plasmid (ALC2906), the bacterial chromosome (Xen29 and Xen40) or a stable plasmid (Xen36). ALC2906 had increased bioluminescent signals through day 10, after which the signals became undetectable. In contrast, Xen29, Xen40 and Xen36 had increased bioluminescent signals through 42 days with the highest signals observed with Xen36. ALC2906, Xen29 and Xen40 induced significantly more inflammation than Xen36 as measured by in vivo EGFP-neutrophil florescence of LysEGFP mice. All four strains induced comparable biofilm formation as determined by variable-pressure scanning electron microscopy. Using a titanium implant, Xen36 had higher in vivo bioluminescence signals than Xen40 but had similar biofilm formation and adherent bacteria. In conclusion, Xen29, Xen40 and especially Xen36, which had stable bioluminescence constructs, are feasible for long-term in vivo monitoring of bacterial burden and biofilm formation to study chronic post-arthroplasty infections and potential antimicrobial interventions.

Summary

The effects of botulinum neurotoxin A on the passive mechanical properties of skeletal muscle have not been investigated, but may have significant impact in the treatment of neuromuscular disorders including spasticity. Single fiber and fiber bundle passive mechanical testing was performed on rat muscles treated with botulinum neurotoxin A. Myosin heavy chain and titin composition of single fibers was determined by gel electrophoresis. Muscle collagen content was determined using a hydroxyproline assay. Neurotoxin-treated single fiber passive elastic modulus was reduced compared to control fibers (53.00 kPa versus 63.43 kPa). Fiber stiffness and slack sarcomere length were also reduced compared to control fibers and myosin heavy chain composition shifted from faster to slower isoforms. Average titin molecular weight increased 1.77% after treatment. Fiber bundle passive elastic modulus increased following treatment (168.83 kPa versus 75.14 kPa). Bundle stiffness also increased while collagen content per mass of muscle tissue increased 38%. Injection of botulinum neurotoxin A produces an effect on the passive mechanical properties of normal muscle that is opposite to the changes observed in spastic muscles.

Summary

It is important to know the magnitude and patterns of joint loading in people with knee osteoarthritis (OA), since altered loads are implicated in onset and progression of the disease. We used an EMG-driven forward dynamics model to estimate joint loads during walking in a subject with knee OA and a healthy control subject. Kinematic, kinetic, and surface EMG data were used to predict muscle forces using a Hill-type muscle model. The muscle forces were used to balance the frontal plane moment to obtain medial and lateral condylar loads. Loads were normalized to body weight (BWs) and the mean of three trials taken. The OA subject had greater medial and lower lateral loads compared to the control subject. 75 to 80% of the total load was borne on the medial compartment in the control subject, compared to 90 to 95% in the OA subject. In fact, complete lateral unloading occurred during midstance for the OA subject. Loading for the healthy subject was consistent with the data from instrumented knee studies. In the future, the model can be used to analyze the impact of various interventions to reduce the loads on the medial compartment in people with knee OA.

The host response and remodeling of ECM scaffolds are believed to be critical determinants of success or failure in repair or reconstructive procedures. Host response has been investigated in subcutaneous or abdominal wall implantation models. The extent to which evaluation of the host response to ECM intended for tendon or ligament repair should be performed in an orthotopic site is not known. This study compared the host response to human-derived fascia lata ECM among various implantation sites in the rat model. Results showed that a xenograft in the rat shoulder does not exhibit a different host response at 7 days from xenograft in the body wall, suggesting that either site may be appropriate to study the early host response to biologic grafts as well as the effect of various treatments aimed to modify the early host response. By 28 days, a xenograft in the rat shoulder does elicit a unique host response from that seen in the body wall. Therefore, it may be more appropriate to use an orthotopic shoulder model for investigating the long-term host response and remodeling of biologic grafts to be used for rotator cuff repair.

During neonatal development, tendons undergo a well orchestrated process whereby extensive structural and compositional changes occur in synchrony to produce a normal tissue. Conversely, during the repair response to injury, structural and compositional changes occur, but a mechanically inferior tendon is produced. As a result, developmental processes have been postulated as a potential paradigm through which improved adult tissue healing may occur. By examining injury at distinctly different stages of development, vital information can be obtained into the structure-function relationships in tendon. The mouse is an intriguing developmental model due to the availability of assays and genetically altered animals. However, it has not previously been used for mechanical analysis of healing tendon due to the small size and fragile nature of neonatal tendons. The objective of this study was to evaluate the differential healing response in tendon at two distinct stages of development through mechanical, compositional, and structural properties. To accomplish this, a new in vivo surgical model and mechanical analysis method for the neonatal mouse Achilles tendons were developed. We demonstrated that injury during early development has an accelerated healing response when compared to injury during late development. This accelerated healing model can be used in future mechanistic studies to elucidate the method for improved adult tendon healing.

Deficiencies in folate lead to increased serum concentrations of homocysteine (Hcy), which is known as hyperhomocysteinemia (HHcy), is associated with bone disorders. Although, homocysteine (Hcy) accumulates collagen in bone and contribute to decrease in bone strength. The mechanism of Hcy induced bone loss and remodeling is unclear. Therefore, the present study was aimed to determine the role of folic acid in genetically HHcy associated decrease in bone blood flow and remodeling. Wildtype (WT) and cystathionine-β-synthase heterozygous (CBS+/−) mice were used in this study and supplemented with or without folic acid (FA 300 mg/kg, Hcy reducing agent) in drinking water for 6 weeks. The tibial bone blood flow was measured by laser Doppler and ultrasonic flow probe method. The tibial bone density was assessed by dual energy X-ray absorptiometry. The bone homogenates were analyzed for oxidative stress,NOX-4 as oxidative marker and thioredoxin-1 (Trx-1) as anti-oxidant marker, bone remodeling (MMP-9) and bio-availability of nitric oxide (eNOS/iNOS/NO) by Western blot method. The results suggested that there was decrease in tibial blood flow in CBS+/− mice. The bone density was also reduced in CBS+/− mice. There was an increase in NOX-4, iNOS, MMP -9 protein as well as MMP-9 activity in CBS+/− mice and decrease in Trx-1, eNOS protein levels, in part by decreasing NO bio-availability in CBS+/− mice. Interestingly, these effects were ameliorated by folic acid and suggested that folic acid supplementation may have therapeutic potential against genetically HHcy induced bone loss.

It is presumed that poor intervertebral disc cell nutrition is a contributing factor in degeneration, and is exacerbated by vertebral endplate sclerosis. Yet, quantitative relationships between endplate morphology and degeneration are unavailable. We investigated how endplate bone microstructure relates to indices of disc degeneration, such as morphologic grade, proteoglycan content, and cell density.

Intervertebral core samples [n=96, 14 subjects, L1–L5 level, ages 35–85 (64±16 yrs.), degeneration grade 1(n=4), grade 2(n=32), grade 3(n=44), grade 4(n=10), grade 5(n=6)] that included subchondral bone, cartilage endplate and adjacent nucleus were harvested from human cadaveric lumbar spines. The morphology of the vertebral endplate was analyzed using μCT and the adjacent nucleus tissue was collected for biochemical and cellular analyses. Relationships between vertebral endplate morphology and adjacent disc degeneration were analyzed.

Contrary to the prevailing notion, vertebral endplate porosity increased between 50 and 130% and trabecular thickness decreased by between 20 and 50% with advancing disc degeneration (p<0.05). We also observed that nucleus cell density increased (R2=0.33, p<0.05) and proteoglycan content decreased (R2=0.47, p<0.05) as the endplate became more porous.

Our data suggest that endplate sclerosis is not a fundamental factor contributing to disc degeneration. Rather, the opposite was observed in our samples, as the endplate became progressively more porous with age and degeneration. Since ischemic disc cell behavior is commonly associated with degenerative change, this may be related to other factors such as the quality of vertebral capillaries, as opposed to decreased permeability of intervening tissues.

Previous studies have demonstrated that Notch signaling regulates endochondral and intramembranous bone formation by controlling cell proliferation and differentiation. Notch signaling has also been shown to regulate healing in a variety of tissues. The objective of this study was to characterize and compare activation of the Notch signaling pathway during endochondral and intramembranous bone fracture healing using tibial fracture and calvarial defect injury models, respectively. Bilateral tibial fractures or bilateral 1.5 mm diameter calvarial defects were created in mice, and tissues were harvested at 0, 5, 10 and 20 days post-fracture. Gene expression of Notch signaling components was upregulated during both tibial fracture and calvarial defect healing, with expression generally higher during tibial fracture healing. The most highly expressed ligand and receptor during healing, Jag1 and Notch2 (specifically the activated receptor, known as NICD2), were similarly localized in mesenchymal cells during both modes of healing, with expression decreasing during chondrogenesis, but remaining present in osteoblasts at all stages of maturity. Results suggest that in addition to embryological bone development, Notch signaling regulates both endochondral and intramembranous bone healing.

Management of various tumor metastases to bone has dramatically improved, but this is not so for renal cell carcinoma (RCC), which is a difficult surgical problem due to its great vascularity. Furthermore, the unique mechanisms that mediate RCC vasculogenesis in bone remain unknown. To understand this process we developed a xenograft model that recapitulates highly vascular RCC vs. less vascular tumors that metastasize to bone. Human tumor cell lines of RCC (786-O), prostate cancer (PC3), lung cancer (A549), breast cancer (MDA-MB231) and melanoma (A375) were transfected with firefly luciferase (Luc), injected into the tibiae of nude mice, and differences in growth, osteolysis and vascularity were assessed by longitudinal bioluminescent imaging (BLI), micro-CT for measurement of calcified tissues and vascularity and histology. The results showed that while RCC-Luc has reduced growth and osteolytic potential vs. the other tumor lines, it displayed a significant increase in vascular volume (p<0.05). This expansion was due to 3- and 5-fold increases in small and large vessel numbers respectively. In vitro gene expression profiling revealed that RCC-Luc expresses significantly (p<0.05) more vegf-a (10-fold) and 20-30-fold less ang-1 vs. the other lines. These data demonstrate the utility of this model to study the unique vasculogenic properties of RCC bone metastases.

Summary

Patellofemoral pain is characterized by pain behind the kneecap and is often thought to be due to high stress at the patellofemoral joint. While we cannot measure bone stress in vivo, we can visualize bone metabolic activity using 18F NaF PET/CT, which may be related to bone stress. Our goals were to use 18F NaF PET/CT to evaluate whether subjects with patellofemoral pan exhibit elevated bone metabolic activity and to determine whether bone metabolic activity correlates with pain intensity. We examined 20 subjects diagnosed with patellofemoral pain. All subjects received an 18F NaF PET/CT scan of their knees. Uptake of 18F NaF in the patella and trochlea was quantified by computing the standardized uptake value and normalizing by the background tracer uptake in bone. We detected increased tracer uptake in 85% of the painful knees examined. We found that the painful knees exhibited increased tracer uptake compared to the pain-free knees of four subjects with unilateral pain (p=0.0006). We also found a correlation between increasing tracer uptake and increasing pain intensity (r2 = 0.55; p = 0.0005). The implication of these results is that patellofemoral pain may be related to bone metabolic activity at the patellofemoral joint.

Tendon injuries are major orthopaedic problems that worsen as the population ages. Type-I (Col1) and type-II (Col2) collagens play important roles in tendon midsubstance and tendon-to-bone insertion healing, respectively. Using double transgenic mice, this study aims to spatiotemporally monitor Col1 and Col2 gene expression, histology and biomechanics up to 8 weeks following a full-length patellar tendon injury. Gene expression and histology were analyzed weekly for up to 5 weeks while mechanical properties were measured at 1, 2, 5, and 8 weeks. At week 1, the healing region displayed loose granulation tissue with little Col1 expression. Col1 expression peaked at 2 weeks, but the ECM was highly disorganized and hypercellular. By 3 weeks, Col1 expression had reduced and by 5 weeks, the ECM was generally aligned along the tendon axis. Col2 expression was not seen in the healing midsubstance or insertion at any time point. The biomechanics of the healing tissue was inadequate at all time points, achieving ultimate loads and stiffnesses of 48% and 63% of normal values by 8 weeks. Future studies will further characterize the cells within the healing midsubstance and insertion using tenogenic markers and compare these results to those of tendon cells during normal development.

Tendon stem cells (TSCs) have been proposed to play a major role in the development of tendinopathy, which refers to pathological changes, such as calcification, in affected tendons. Using a human TSC (hTSC) culture model, this study investigated the effects of PGE2, an inflammatory mediator present in injured tendons, on hTSC proliferation and differentiation as well as the molecular mediator for such PGE2-induced effects. We found that PGE2 treatment of hTSCs decreased cell proliferation and caused osteogenic differentiation of hTSCs in a dose- dependent manner. Also, PGE2 treatment of hTSCs induced dose-dependent BMP-2 production in culture, and moreover, addition of BMP-2 to hTSC culture decreased cell proliferation and induced hTSC differentiation into osteoblasts. Finally, addition of BMP-2 antibodies to hTSC culture treated with PGE2 nearly abolished PGE2 effects on both cell proliferation and osteogenic differentiation. Taken together, the findings of this study showed that BMP-2 mediates PGE2-induced reduction of proliferation and osteogenic differentiation of hTSCs. We suggest that such a mechanism may be partially responsible for the formation of calcified tissues in tendinopathic tendons seen in clinical settings.

Platelet-rich plasma (PRP) has shown in vivo potential to stimulate anterior cruciate ligament (ACL) healing at early time points in large animal models. However, in animal models, the healing potential of the ACL is dependent on animal age. In this study, we hypothesized that there are age-dependent differences in ACL cell metabolism, collagen gene expression and the ability of the cells to respond to growth factors in platelet-rich plasma (PRP). To test this hypothesis, ACL cells were obtained from skeletally immature, adolescent and adult pigs and cultured in a collagen type I hydrogel with or without PRP for 14 days. When cultured in collagen-only hydrogel, ACL cells from adult pigs had a 19% lower apoptotic rate as compared to immature pigs (p=0.001) and a 25% higher cellular metabolic activity as compared to adolescent pigs (p=0.006). The addition of PRP to the collagen hydrogel resulted in a significantly increased cellular metabolic activity, reduced apoptotic rate and stimulation of collagen production in the cells from the immature and adolescent animals (p<0.05 for all comparisons) but had less of an effect on adult cells. These findings suggest that skeletal maturity may influence ACL cells’ metabolic activity, apoptosis, collagen production, and response to PRP.

The sulcus angle has been widely used in the literature as a measure of trochlear morphology. Recently, lateral trochlear inclination and trochlear angle have been reported as alternatives. The purpose of this study was to determine the association between measures of trochlear morphology and patellofemoral joint (PFJ) cartilage damage and bone marrow lesions (BMLs). 907 knees were selected from the Multicenter Osteoarthritis Study, a cohort study of persons aged 50-79 years with or at risk for knee OA. Trochlear morphology was measured using lateral trochlear inclination, trochlear angle, and sulcus angle on axial MRI images; cartilage damage and BMLs were graded on MRI. We determined the association between quartiles of each trochlear morphology level with the presence or absence of cartilage damage and BMLs in the PFJ using logistic regression. The strongest associations were seen with lateral trochlear inclination and lateral PFJ cartilage damage and BMLs, with knees in the lowest quartile (flattened lateral trochlea) having more than two times the odds of lateral cartilage damage and BMLs compared to those in the highest quartile (p<0.0001). Lateral trochlear inclination may be the best method for assessment of trochlear morphology as it was strongly association with structural damage in the PFJ.

PURPOSE

Changes in the insertion site of the ACL after enhanced suture repair with collagen-platelet-composites (CPC) have not yet been defined. In this study, we hypothesized that fibroblasts and osteoclasts would participate in generating histologic changes in insertion site morphology after transection and bioenhanced repair of the ACL, and that these changes would be age-dependent.

METHODS

Skeletally immature, adolescent, and adult Yucatan mini-pigs underwent ACL transection and bioenhanced suture repair. The histologic response to repair of the insertion site was evaluated at 1, 2, 4 and 15 weeks.

RESULTS

In young and adolescent animals treated with bioenhanced suture repair with CPC, changes in the insertion site included: (1) fibroblastic proliferation with loss and return of collagen alignment in the fibrous zone; (2) osteoclastic resorption within fibrocartilage zones at 2–4 weeks; and (3) partial reappearance of fibrocartilage zones at 15 weeks. In adult animals; however, degenerative changes were noted by 15 weeks: (1) loss of parallel arrangement of collagen fibers in the fibrous zone; and (2) increasing disorganization and loss of columnation of chondrocytes in the fibrocartilage zone.

CONCLUSIONS

These results suggest that fibroblasts and osteoclasts mediate histologic changes at the insertion site during bioenhanced suture repair of the ACL which may prevent insertion site degeneration, and that the magnitude of these changes may be a function of skeletal maturity.

Injuries to the inner regions of the knee meniscus do not heal and can result in degenerative changes to the articular surface, ultimately leading to osteoarthritis. A possible stimulus to enhance meniscus healing is to use electric fields that induce galvanotaxis. In this study, a novel characterization of the effects of direct current electric fields on migration characteristics of meniscus cells was performed. Primary and passaged inner and outer meniscus cells were exposed to varying electric field strengths from 0 to 6 V/cm. Cell migration was tracked using time lapse digital photography, and cell displacement and cathodal direct velocity were quantified. Cytoskeletal staining was performed to examine actin distribution and nuclear content. Cell adhesion strength was quantified as a function of wall shear stress. Meniscus cells exhibited cathodal migration and cell elongation perpendicular to the applied electric field accompanied by actin reorganization. Outer meniscus cells migrated quicker and exhibited lower adhesion strengths when compared to inner meniscus cells. Passaged cells exhibited higher migration characteristics when compared to primary cells. Overall, this study demonstrated that electric fields can significantly enhance and direct meniscus cell migration and suggests the potential for their incorporation in strategies of meniscus repair and tissue engineering.

Carpal tunnel mechanics is relevant to our understanding of median nerve compression in the tunnel. The compliant characteristics of the tunnel strongly influence its mechanical environment. We investigated the distensibility of the carpal tunnel in response to tunnel pressure. A custom balloon device was designed to apply controlled pressure. Tunnel cross sections were obtained using magnetic resonance imaging (MRI) to derive the relationship between carpal tunnel pressure and morphological parameters at the hook of hamate. The results showed that the cross-sectional area (CSA) at the level of the hook of hamate increased, on average, by 9.2% and 14.8% at 100 mmHg and 200 mmHg, respectively. The increased CSA was attained by a shape change of the cross section, displaying increased circularity. The increase in CSA was mainly attributable to the increase of area in the carpal arch region formed by the transverse carpal ligament. The narrowing of the carpal arch width was associated with an increase in the carpal arch. We concluded that the carpal tunnel is compliant to accommodate physiological variations of the carpal tunnel pressure, and that the increase in tunnel CSA is achieved by increasing the circularity of the cross section.

Development of novel therapeutic approaches to repair fracture non-unions remains a critical clinical necessity. We evaluated the capacity of human embryonic stem cell (hESC)-derived mesenchymal stem/stromal cells (MSCs) to induce healing in a fracture non-union model in rats. In addition, we placed these findings in the context of parallel studies using human bone marrow MSCs (hBM-MSCs) or a no cell control group (n = 10 to 12 per group). Preliminary studies demonstrated that both for hESC-derived MSCs and hBM-MSCs, optimal induction of fracture healing required in vitro osteogenic differentiation of these cells. Based on biomechanical testing of fractured femurs, maximum torque and stiffness were significantly greater in the hBM-MSC as compared to the control group that received no cells; values for these parameters in the hESC-derived MSC group were intermediate between the hBM-MSC and control groups, and not significantly different from the control group. However, some evidence of fracture healing was evident by X-ray in the hESC-derived MSC group. Our results thus indicate that while hESC-derived MSCs may have potential to induce fracture healing in non-unions, hBM-MSCs function more efficiently in this process. Additional studies are needed to further modify hESCs to achieve optimal fracture healing by these cells.

Objective

This study investigated the effects of different doses of hypertonic dextrose injection on the carpal tunnel subsynovial connective tissue (SSCT) and median nerve in a rabbit model.

Methods

Thirty-eight New Zealand white rabbits weighing 4.0–4.5 kg were used. One forepaw carpal tunnel was randomly injected with one of five different treatments: saline-single injection; saline-two injections one week apart; 10% dextrose-single injection; 20% dextrose-single injection; or 10% dextrose- two injections one week apart. Animals were sacrificed at 12 weeks after the initial injection and were evaluated by electrophysiology (EP), SSCT mechanical testing and histology.

Results

There were significant increases in the energy absorption of the SSCT in the 10% dextrose double injection group compared to the saline injection groups. SSCT stiffness was also significantly increased in the 10% dextrose-double injection group compared to the other groups. There was a significant increase in the thickness of the SSCT in the 10% dextrose-double injection group compared to the saline-single injection group and a significant decrease in the nerve short-long diameter ratio in the 10% dextrose double injection group compared to the saline-single injection group. There were no changes in EP among the groups.

Conclusions

SSCT fibrosis is present for up to 12 weeks after dextrose injection; multiple injections have bigger effects, including what appears to be a secondary change in nerve flattening. This model may be useful to study the effects of external fibrosis on nerve morphology and physiology, such as occurs clinically in carpal tunnel syndrome.

Research has shown that mechanical loading affects matrix biosynthesis of intervertebral disc (IVD) cells; however the pathway(s) to this effect is currently unknown. Cellular matrix biosynthesis is an energy demanding process. The objective of this study was to investigate the effects of static and dynamic compressive loading on energy metabolism of IVD cells. Porcine annulus fibrosus (AF) and nucleus pulposus (NP) cells seeded in 2% agarose were used in this experiment. Experimental groups included 15% static compression and 0.1 and 1 Hz dynamic compression at 15% strain magnitude for 4 hours. ATP, lactate, glucose and nitric oxide (NO) contents in culture media, and ATP content in cell-agarose construct were measured using biochemical assays. While the total ATP content of AF cells was promoted by static and dynamic loading, only 1 Hz dynamic loading increased total ATP content of NP cells. Increases in lactate production and glucose consumption of AF cells suggest that ATP production via glycolysis is promoted by dynamic compression. ATP release and NO production of AF and NP cells were significantly increased by dynamic loading. Thus, this study clearly illustrates that static and dynamic compressive loading affect IVD cell energy production while cellular responses to mechanical loading were both cell type and compression type dependent.

No permanent, reliable artificial tendon exists clinically. Our group developed the OrthoCoupler™ device as a versatile connector, fixed at one end to a muscle, and adaptable at the other end to inert implants such as prosthetic bones or to bone anchors. The objective of this study was to evaluate four configurations of the device to replace the extensor mechanism of the knee in goats. Within muscle, the four groups had: (A) needle-drawn uncoated bundles, (B) needle-drawn coated bundles, (C) barbed uncoated bundles, and (D) barbed coated bundles. The quadriceps tendon, patella, and patellar tendon were removed from the right hind limb in 24 goats. The four groups (n=6 for each) were randomly assigned to connect the quadriceps muscle to the tibia (with a bone plate). Specimens were collected from each operated leg and contralateral unoperated controls both for mechanical testing and histology at 90 days post-surgery. In strength testing, maximum forces in the operated leg (vs. unoperated control) were 1288±123 N (vs. 1387±118 N) for group A, 1323±144 N (vs. 1396±779 N) for group B, 930±125 N (vs. 1337±126 N) for group C, and 968±109 N (vs. 1528±146 N) for group D (mean ± SEM). The strengths of the OrthoCoupler™ legs in the needled device groups were equivalent to unoperated controls (p=0.6), while both barbed device groups had maximum forces significantly lower than their controls (p=0.001). We believe this technology will yield improved procedures for clinical challenges in orthopaedic oncology, revision arthroplasty, tendon transfer, and tendon injury reconstruction.

Alterations in microdamage morphology and accumulation are typically attributed to impaired remodeling, but may also result from changes in microdamage initiation and propagation. Such alterations are relevant for cancellous bone with high metabolic activity and numerous bone quality changes. This study investigates the role of trabecular microarchitecture on morphology and accumulation of microdamage in human cancellous bone. Trabecular bone cores from donors of varying ages and bone volume fraction (BV/TV) were separated into high and low BV/TV groups. Samples were subjected to no load or uniaxial compression to 0.6% (pre-yield) or 1.1% (post-yield) strain. Microdamage was stained with lead uranyl acetate and specimens were imaged via microcomputed tomography to quantify microdamage and determine its morphology in three-dimensions (3D). Donors with high BV/TV had greater post yield strain and were tougher than low BV/TV donors. High BV/TV bone had less microdamage than low BV/TV bone under post- but not pre-yield loading. Microdamage under both loading conditions showed significant correlations with microarchitecture and BV/TV, but the key predictor was structure model index (SMI). As SMI increased (more trabecular rods), microdamage morphology became crack-like. Thus, low BV/TV and increased SMI have strong influences on microdamage accumulation in bone through altered initiation.

Instability is a significant concern in total hip arthroplasty, particularly when there is structural compromise of the capsule due to pre-existing pathology or due to necessities of surgical approach. An experimentally grounded fiber-direction-based finite element model of the hip capsule was developed, and was integrated with an established three-dimensional model of impingement/dislocation. Model validity was established by close similarity to results from a cadaveric experiment in a servohydraulic hip simulator. Parametric computational runs explored effects of graded levels of capsule thickness, of regional detachment from the capsule’s femoral or acetabular insertions, of surgical incisions of capsule substance, and of capsule defect repairs. Depending strongly upon the specific site, localized capsule defects caused varying degrees of construct stability compromise, with several specific situations involving over 60% decrement in dislocation resistance. Construct stability was returned substantially toward intact-capsule levels following well conceived repairs, although the suture sites involved were often at substantial risk of failure. These parametric model results underscore the importance of retaining or robustly repairing capsular structures in total hip arthroplasty, in order to maximize overall construct stability.