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Background The purpose of this study was to compare initial fixation strength between various stemless and stemmed humeral components and to correlate implant fixation strength with bone mineral density (BMD). Methods Five humeral stem designs were investigated: Stemless-A (four hollow fins), Stemless-B (central body, three solid fins), Stemless-C (central screw, peripheral rim-fit), Short stem (50 mm), and Standard stem (130 mm). Fifty cadaveric human humerii were obtained and divided into five groups. BMD within the humeral head was determined for all samples. The mean BMD was similar between groups. The 25 samples with the lowest and highest BMDs were categorized as “Low” and “High,” respectively, with a BMD threshold of 0.35 g/cm2, creating BMD subgroups. After implantation, each sample underwent a standardized biomechanical testing protocol, with axial loading followed by torsional loading. Sensors attached to the specimen recorded micromotion throughout testing. Axial loading consisted of cyclic loading for 100 cycles at 3 peak forces (220, 520, and 820 N). Torsional loading consisted of 100 cycles of internal/external rotation at 0.1 Hz at 6 peak torques, or until failure (±2.5, 5, 7.5, 10, 12.5, and 15 Nm). Failure was defined as the torque at which any bone fracture, implant detachment from anchor/stem, or an excess of 50° internal/external rotation occurred. Groups and BMD subgroups were compared. Results At maximal axial loading, Stemless-B demonstrated greater micromotion (540 μm) than Stemless-C (192 μm) (P = .003). Stemless-B and Stemless-A (387 μm) also had greater micromotion than Short stem (118 μm, P Conclusion Stemless humeral implants should be used with caution in low-BMD settings ( Level of evidence Basic Science Study; Cadaveric Study

Fractures in the femoral neck are a common occurrence in individuals with osteoporosis. Many mouse models have been developed to assess disease states and therapies, with biomechanical testing as a primary outcome measure. However, traditional biomechanical testing focuses on torsion or bending tests applied to the midshaft of the long bones. This is not typically the site of high-risk fractures in osteoporotic individuals. Therefore, a biomechanical testing protocol was developed that tests the femoral necks of murine femurs in cantilever bending loading to replicate better the types of fractures experienced by osteoporosis patients. Since the biomechanical outcomes are highly dependent on the flexural loading direction relative to the femoral neck, 3D printed guides were created to maintain a femoral shaft at an angle of 20° relative to the loading direction. The new protocol streamlined the testing by reducing variability in alignment (21.6° ± 1.5°, COV = 7.1%, n = 20) and improved reproducibility in the measured biomechanical outcomes (average COV = 26.7%). The new approach using the 3D printed guides for reliable specimen alignment improves rigor and reproducibility by reducing the measurement errors due to specimen misalignment, which should minimize sample sizes in mouse studies of osteoporosis.

Massive craniofacial bone loss poses a clinical challenge to maxillofacial surgeons. Structural bone allografts are readily available at tissue banks but are rarely used due to a high failure rate. Previous studies showed that intermittent administration of recombinant parathyroid hormone (rPTH) enhanced integration of allografts in a murine model of calvarial bone defect. To evaluate its translational potential, the hypothesis that rPTH would enhance healing of a mandibular allograft in a clinically relevant large animal model of mandibulectomy was tested. Porcine bone allografts were implanted into a 5-cm-long continuous mandible bone defect in six adult Yucatan minipigs, which were randomized to daily intramuscular injections of rPTH (1.75 μg/kg) and placebo (n = 3). Blood tests were performed on Day 56 preoperation, Day 0 and on Day 56 postoperation. Eight weeks after the surgery, bone healing was analyzed using high-resolution X-ray imaging (Faxitron and micro computed tomography [CT]) and three-point bending biomechanical testing. The results showed a significant 2.6-fold rPTH-induced increase in bone formation (p = 0.02). Biomechanically, the yield failure properties of the healed mandibles were significantly higher in the rPTH group (yield load: p < 0.05; energy to yield: p < 0.01), and the post-yield displacement and energy were higher in the placebo group (p < 0.05), suggesting increased mineralized integration of the allograft in the rPTH group. In contrast to similar rPTH therapy studies in dogs, no signs of hypercalcemia, hyperphosphatemia, or inflammation were detected. Taken together, we provide initial evidence that rPTH treatment enhances mandibular allograft healing in a clinically relevant large animal model.

Background:Bony Bankart lesions can be encountered during treatment of shoulder instability. Current arthroscopic bony Bankart repair techniques involve intra-articular suture placement, but the effect of these repair techniques on the integrity of the humeral head articular surface warrants further investigation.Purpose:To quantify the degree of humeral head articular cartilage damage secondary to current arthroscopic bony Bankart repair techniques in a cadaveric model.Study Design:Controlled laboratory study.Methods:Testing was performed in 13 matched pairs of cadaveric glenoids with simulated bony Bankart fractures, with a defect width of 25% of the glenoid diameter. Half of the fractures were repaired with a double-row technique, while the contralateral glenoids were repaired with a single-row technique. Samples were subjected to 20,000 cycles of internal-external rotation across a 90° arc at 2 Hz after a compressive load of 750 N, or 90% body weight (whichever was less) was applied to simulate wear. Cartilage defects on the humeral head were quantified through a custom MATLAB script. Mean cartilage cutout differences were analyzed by the Wilcoxon rank-sum test.Results:Both single- and double-row repairs showed macroscopic damage. The histomorphometric analysis demonstrated that the double-row technique resulted in a significantly ( P = .036) more chondral damage (mean, 57,489.1 µm2; SD, 61,262.2 µm2) than the single-row repair (mean, 28,763.5 µm2; SD, 24,4990.2 µm2).Conclusion:Both single-row and double-row arthroscopic bony Bankart fixation techniques resulted in damage to the humeral head articular cartilage in the concavity-compression model utilized in this study. The double-row fixation technique resulted in a significantly increased cutout to the humeral head cartilage after simulated wear in this cadaveric model.Clinical Relevance:This study provides data demonstrating that placement of intra-articular suture during arthroscopic bony Bankart repair techniques may harm the humeral head cartilage. While the double-row repair of bony Bankart lesions is more stable, it results in increased cartilage damage. These findings suggest that alternative, cartilage-sparing arthroscopic techniques for bony Bankart repair should be investigated.

Background:Previous studies comparing stability between single- and double-row arthroscopic bony Bankart repair techniques focused only on the measurements of tensile forces on the bony fragment without re-creating a more physiologic testing environment.Purpose:To compare dynamic stability and displacement between single- and double-row arthroscopic repair techniques for acute bony Bankart lesions in a concavity-compression cadaveric model simulating physiologic conditions.Study Design:Controlled laboratory study.Methods:Testing was performed on 13 matched pairs of cadaveric glenoids with simulated bony Bankart fractures with a defect width of 25% of the inferior glenoid diameter. Half of the fractures were repaired with a double-row technique, and the contralateral glenoids were repaired with a single-row technique. To determine dynamic biomechanical stability and ultimate step-off of the repairs, a 150-N load and 2000 cycles of internal-external rotation at 1 Hz were applied to specimens to simulate early rehabilitation. Toggle was quantified throughout cycling with a coordinate measuring machine. Three-dimensional spatial measurements were calculated. After cyclic loading, the fracture displacement was measured.Results:The bony Bankart fragment–glenoid initial step-off was found to be significantly greater ( P < .001) for the single-row technique (mean, 896 µm; SD, 282 µm) compared with the double-row technique (mean, 436 µm; SD, 313 µm). The motion toggle was found to be significantly greater ( P = .017) for the single-row technique (mean, 994 µm; SD, 711 µm) compared with the double-row technique (mean, 408 µm; SD, 384 µm). The ultimate interface displacement was found to be significantly greater ( P = .029) for the single-row technique (mean, 1265 µm; SD, 606 µm) compared with the double-row technique (mean, 795 µm; SD, 398 µm).Conclusion:Using a concavity-compression glenohumeral cadaveric model, we found that the double-row arthroscopic fixation technique for bony Bankart repair resulted in superior stability and decreased displacement during simulated rehabilitation when compared with the single-row repair technique.Clinical Relevance:The findings from this study may help guide surgical decision-making by demonstrating superior biomechanical properties (improved initial step-off, motion toggle, and interface displacement) of the double-row bony Bankart repair technique when compared with single-row fixation. The double-row repair construct demonstrated increased stability of the bony Bankart fragment, which may improve bony Bankart healing.

Despite the requirement forScleraxis-lineage (ScxLin) cells during tendon development, the function of ScxLincells during adult tendon repair, post-natal growth, and adult homeostasis have not been defined. Therefore, we inducibly depleted ScxLincells (ScxLinDTR) prior to tendon injury and repair surgery and hypothesized that ScxLinDTRmice would exhibit functionally deficient healing compared to wild-type littermates. Surprisingly, depletion of ScxLincells resulted in increased biomechanical properties without impairments in gliding function at 28 days post-repair, indicative of regeneration. RNA sequencing of day 28 post-repair tendons highlighted differences in matrix-related genes, cell motility, cytoskeletal organization, and metabolism. We also utilized ScxLinDTRmice to define the effects on post-natal tendon growth and adult tendon homeostasis and discovered that adult ScxLincell depletion resulted in altered tendon collagen fibril diameter, density, and dispersion. Collectively, these findings enhance our fundamental understanding of tendon cell localization, function, and fate during healing, growth, and homeostasis.

Bone fragility and fracture risk are assessed by measuring the areal bone mineral density (aBMD) using dual-energy X-ray absorptiometry (DXA). While aBMD correlates with bone strength, it is a poor predictor of fragility fracture risk. Alternatively, fracture toughness assesses the bone’s resistance to crack propagation and fracture, making it a suitable bone quality metric. Here, we explored how femoral midshaft measurements from DXA, micro-computed tomography (μCT), and Raman spectroscopy could predict fracture toughness. We hypothesized that ovariectomy (OVX) decreases aBMD and fracture toughness compared to controls and we can optimize a multivariate assessment of bone quality by combining results from X-ray and Raman spectroscopy. Female mice underwent an OVX (n=5) or sham (n=5) surgery at 3 months of age. Femurs were excised 3 months after ovariectomy and assessed with Raman spectroscopy, μCT, and DXA. Subsequently, a notch was created on the anterior side of the mid-diaphysis of the femurs. Three-point bending induced a controlled fracture that initiated at the notch. The OVX mice had a significantly lower aBMD, cortical thickness, and fracture toughness when compared to controls (p2=0.71, p2=0.92, p

The shortcomings of autografts and allografts in bone defect healing have prompted researchers to develop suitable alternatives. Numerous biomaterials have been developed as bone graft substitutes each with their own advantages and disadvantages. However, in order to test if these biomaterials provide an adequate replacement of the clinical standard, a clinically representative animal model is needed to test their efficacy. In this chapter, we describe a mouse model that establishes a critical sized defect in the mid-diaphysis of the femur to evaluate the performance of bone graft substitutes. This is achieved by performing a femoral ostectomy and stabilization utilizing a femoral plate and titanium screws. The resulting defect enables the bone regenerative potential of bone graft substitutes to be investigated. Lastly, we provide instruction on assessing the torsional strength of the healed femurs to quantitatively evaluate the degree of healing as a primary outcome measure.

Background:Adult acquired flatfoot deformity (AAFD) is a complex and progressive deformity involving the ligamentous structures of the medial peritalar joints. Recent anatomic studies demonstrated that the spring and deltoid ligaments form a greater medial ligament complex, the tibiocalcaneonavicular ligament (TCNL), which provides medial stability to the talonavicular, subtalar, and tibiotalar joints. The aim of this study was to assess the biomechanical effect of a spring ligament tear on the peritalar stability. The secondary aim was to assess the effect of TCNL reconstruction in restoration of peritalar stability in comparison with other medial stabilization procedures, anatomic spring or deltoid ligament reconstructions, in a cadaveric flatfoot model.Methods:Ten fresh-frozen cadaveric foot specimens were used. Reflective markers were mounted on the tibia, talus, navicular, calcaneus, and first metatarsal. Peritalar joint kinematics were captured by a multiple-camera motion capture system. Mild, moderate, and severe flatfoot models were created by sequential sectioning of medial capsuloligament complex followed by cyclic axial loading. Spring only, deltoid only, and combined deltoid-spring ligament (TCNL) reconstructions were performed. The relative kinematic changes were compared using 2-way analysis of variance (ANOVA).Results:Compared with the initial condition, we noted significantly increased valgus alignment of the subtalar joint of 5.1 ± 2.3 degrees ( P = .031) and 5.8 ± 2.7 degrees ( P < .01) with increased size of the spring ligament tear to create moderate to severe flatfoot, respectively. We noted an increased tibiotalar valgus angle of 5.1 ± 2.0 degrees ( P = .03) in the severe model. Although all medial ligament reconstruction methods were able to correct forefoot abduction, the TCNL reconstruction was able to correct both the subtalar and tibiotalar valgus deformity ( P = .04 and P = .02, respectively).Conclusion:The TCNL complex provided stability to the talonavicular, subtalar, and tibiotalar joints. The combined deltoid-spring ligament (TCNL) reconstructions restored peritalar kinematics better than isolated spring or deltoid ligament reconstruction in the severe AAFD model.Clinical Relevance:The combined deltoid-spring ligament (TCNL) reconstruction maybe considered in advanced AAFD with medial peritalar instability: stage IIB with a large spring ligament tear or stage IV.

The use of tamoxifen-inducible models of Cre recombinase in the tendon field is rapidly expanding, resulting in an enhanced understanding of tendon homeostasis and healing. However, the effects of tamoxifen on the tendon are not well-defined, which is particularly problematic given that tamoxifen can have both profibrotic and antifibrotic effects in a tissue-specific manner. Therefore, in the present study, we examined the effects of tamoxifen on tendon homeostasis and healing in male and female C57Bl/6J mice. Tamoxifen-treated mice were compared to corn oil (vehicle)-treated mice. In the "washout" treatment regimen, mice were treated with tamoxifen or corn oil for 3 days beginning 1 week prior to undergoing complete transection and surgical repair of the flexor digitorum longus tendon. In the second regimen, mice were treated with tamoxifen or corn oil beginning on the day of surgery, daily through day 2 postsurgery, and every 48 hours thereafter (D0-2q48) until harvest. All repaired tendons and uninjured contralateral control tendons were harvested at day 14 postsurgery. Tamoxifen treatment had no effect on tendon healing in male mice, regardless of the treatment regimen, while Max load was significantly decreased in female repairs in the Tamoxifen washout group, relative to corn oil. In contrast, D0-2q48 corn oil treatment in female mice led to substantial disruptions in tendon homeostasis, relative to washout corn oil treatment. Collectively, these data clearly define the functional effects of tamoxifen and corn oil treatment in the tendon and inform future use of tamoxifen-inducible genetic models.

Fracture toughness, a bone’s resistance to breaking, is typically measured via invasive mechanical tests. In this ex vivo study on mouse femurs, four Raman spectral features associated with bone properties were significantly correlated to fracture toughness using a partial least squares regression model. By including parameters measured from dual-energy absorptiometry and micro-computed tomography in the model, fracture toughness predictions on ovariectomized mice were significantly lower than a control cohort’s. This shows that meaningful estimates of fracture toughness can be estimated using input parameters obtained non-destructively.

Acute tendon injuries are characterized by excessive matrix deposition that impedes regeneration and disrupts functional improvements. Inflammation is postulated to drive pathologic scar tissue formation, with nuclear factor kappa B (NF-κB) signaling emerging as a candidate pathway in this process. However, characterization of the spatial and temporal activation of canonical NF-κB signaling during tendon healingin vivo, including identification of the cell populations activating NF-κB, is currently unexplored. Therefore, we aimed to determine which cell populations activate canonical NF-κB signaling following flexor tendon repair with the goal of delineating cell-specific functions of NF-κB signaling during scar mediated tendon healing. Immunofluorescence revealed that both tendon cells and myofibroblasts exhibit prolonged activation of canonical NF-κB signaling into the remodeling phase of healing. Using cre-mediated knockout of the canonical NF-κB kinase (IKKβ), we discovered that suppression of canonical NF-κB signaling in Scleraxis-lineage cells increased myofibroblast content and scar tissue formation. Interestingly, Scleraxis-lineage specific knockout of IKKβ increased the incidence of apoptosis, suggesting that canonical NF-κB signaling may be mediating cell survival during tendon healing. These findings suggest indispensable roles for canonical NF-κB signaling during flexor tendon healing.One Sentence SummaryScleraxis-lineage specific knockdown of persistent canonical IKKβ/NF-κB drives scar formation and apoptotic signaling during flexor tendon healing.

Despite the requirement forScleraxis-lineage (ScxLin) cells during tendon development, the function of ScxLincells during adult tendon repair, post-natal growth, and adult homeostasis have not been defined. Therefore, we inducibly depleted ScxLincells (ScxLinDTR) prior to tendon injury and repair surgery and hypothesized that ScxLinDTRmice would exhibit functionally deficient healing compared to wildtype littermates. Surprisingly, depletion of ScxLincells resulted in increased biomechanical properties without impairments in gliding function at 28 days post-repair, indicative of regeneration. RNA sequencing of day 28 post-repair tendons highlighted differences in matrix-related genes, cell motility, cytoskeletal organization, and metabolism. We also utilized ScxLinDTRmice to define the effects on post-natal tendon growth and adult tendon homeostasis and discovered that adult ScxLincell depletion resulted in altered tendon collagen fibril diameter, density, and dispersion. Collectively, these findings enhance our fundamental understanding of tendon cell localization, function, and fate during healing, growth, and homeostasis.

Background Forearm fractures are one of the top three most common fractures in children. Treatment often includes immobilizing the arm in a cast extending above the elbow to help maintain fracture reduction and alignment. Complications from circumferential casting can occur including swelling in the forearm that can lead to neurovascular complications. About 16% of children require splitting of the cast to relieve the increased pressure. Our study investigates the impact the location of the split has on cast bending stiffness in an above elbow cast model. Methods A Sawbones© pediatric forearm model was used for application of a hybrid plaster-fiberglass cast to simulate treatment of a pediatric forearm fracture. The plaster was allowed to set for 20 minutes followed by application of a single fiberglass layer. The casts set for at least 24 hours and were then left intact or split along one of their 4 axes. Once categorized, the casts were subjected to biomechanical testing using an Instron ElectroPlus 10000 with a 3-point bending set up. The casts were tested until failure, and the load versus displacement curves were analyzed. Each category of casts was tested five times from both a volar and dorsal direction. Results When loaded dorsal to volar, intact casts were significantly stiffer than those split along the dorsal, radial, or volar surfaces (p=0.0062, 0.0267, 0.0024 respectively). There was no significant difference when comparing one axis of longitudinal split to another. Intact casts showed a significantly higher load to failure than those split along the radial border (p=0.0168). When loaded volar to dorsal, intact casts were significantly stiffer than those split along any axis. Intact casts showed a significantly higher maximum load to failure than those split along the radial or ulnar border (p=0.0247, 0.0112 respectively). Conclusion Consideration should be given to splitting above elbow casts along the volar or dorsal surface, as those split along the radial or ulnar border tend to have lower maximum load to failure. Clinical relevance To analyze the effect of splitting an above elbow cast on bending stiffness.

Flexor tendon injuries heal with excessive scar tissue that limits range of motion and increases incidence of re-rupture. The molecular mechanisms that govern tendon healing are not well defined. Both the canonical nuclear factor kappa B (NF-κB) and mitogen activated protein kinase (MAPK) pathways have been implicated in tendon healing. The gene NFKB1 (proteins p105/p50) is involved in both NF-κB and MAPK signaling cascades. In the present study, we tested the hypothesis that global NFKB1 deletion would increase activation of both NF-κB and MAPK through loss of signaling repressors, resulting in increased matrix deposition and altered biomechanical properties. As hypothesized, NFKB1 deletion increased activation of both NF-κB and MAPK signaling. While gliding function was not affected, NFKB1 deletion resulted in tendons that were significantly stiffer and trending towards increased strength by four weeks post-repair. NFKB1 deletion resulted in increased collagen deposition, increase macrophage recruitment, and increased presence of myofibroblasts. Furthermore, NFKB1 deletion increased expression of matrix-related genes (Col1a1, Col3a1), macrophage-associated genes (Adgre1, Ccl2), myofibroblast markers (Acta2), and general inflammation (Tnf). Taken together, these data suggest that increased activation of NF-κB and MAPK via NFKB1 deletion enhance macrophage and myofibroblast content at the repair, driving increased collagen deposition and biomechanical properties.

Osteomyelitis is a chronic bone infection that is often treated with adjuvant antibiotic-impregnated poly(methyl methacrylate) (PMMA) cement spacers in multi-staged revisions. However, failure rates remain substantial due to recurrence of infection, which is attributed to the poor performance of the PMMA cement as a drug release device. Hence, the objective of this study was to design and evaluate a bioresorbable calcium phosphate scaffold (CaPS) for sustained antimicrobial drug release and investigate its efficacy in a murine model of femoral implant-associated osteomyelitis. Incorporating rifampin and sitafloxacin, which are effective against bacterial phenotypes responsible for bacterial persistence, into 3D-printed CaPS coated with poly(lactic co-glycolic) acid, achieved controlled release for up to two weeks. Implantation into the murine infection model resulted in decreased bacterial colonization rates at 3- and 10-weeks post-revision for the 3D printed CaPS in comparison to gentamicin-laden PMMA. Furthermore, a significant increase in bone formation was observed for 3D printed CaPS incorporated with rifampin at 3 and 10 weeks. The results of this study demonstrate that osteoconductive 3D printed CaPS incorporated with antimicrobials demonstrate more efficacious bacterial colonization outcomes and bone growth in a single-stage revision in comparison to gentamicin-laden PMMA requiring a two-stage revision.

Identification of pro-regenerative approaches to improve tendon healing is critically important as the fibrotic healing response impairs physical function. In the present study we tested the hypothesis that S100a4 haploinsufficiency or inhibition of S100a4 signaling improves tendon function following acute injury and surgical repair in a murine model. We demonstrate that S100a4 drives fibrotic tendon healing primarily through a cell non-autonomous process, with S100a4 haploinsufficiency promoting regenerative tendon healing. Moreover, inhibition of S100a4 signaling via antagonism of its putative receptor, RAGE, also decreases scar formation. Mechanistically, S100a4 haploinsufficiency decreases myofibroblast and macrophage content at the site of injury, with both cell populations being key drivers of fibrotic progression. Moreover, S100a4-lineage cells become α-SMA+ myofibroblasts, via loss of S100a4 expression. Using a combination of genetic mouse models, small molecule inhibitors and in vitro studies we have defined S100a4 as a novel, promising therapeutic candidate to improve tendon function after acute injury.

Identification of pro-regenerative approaches to improve tendon healing is of critical importance given the diminished quality of life and physical function that accompanies the typical fibrotic response to tendon injury. S100a4 modulates fibrosis through tissue-type dependent mechanisms, and the role of S100a4 in fibrotic, scar-mediated tendon healing has not been established. In the present study we tested the hypothesis that inhibition of S100a4 improves tendon function following acute injury and surgical repair. We demonstrate cell non-autonomous functions of S100a4 as S100a4 haploinsufficiency promotes regenerative tendon healing, including decreased scar formation and improved mechanical properties. Moreover, inhibition of S100a4 via antagonism of its putative receptor, the Receptor for Advanced Glycation Endproducts (RAGE), also decreases scar formation. Mechanistically, knock-down of S100a4 decreases myofibroblast and macrophage content at the site of injury, with both cell populations being key drivers of fibrotic progression. In contrast, S100a4+ cell depletion displays time-dependent effects on scar formation, and consistent impairments in restoration of mechanical properties, indicating a critical role for these cells in re-establishing tendon strength after injury. Finally, we demonstrate, that S100a4-lineage cells become α-SMA+ myofibroblasts, via loss of S100a4 expression. Using a combination of genetic mouse models, small molecule inhibitors and in vitro studies we have defined S100a4 as a novel, promising therapeutic candidate to improve tendon function after acute injury.

Type I and Type II Diabetes dramatically impair skeletal health. Altered Insulin Receptor (IR) signaling is a common feature of both diseases, and insulin has potent bone anabolic functions. Several previous studies have demonstrated that loss of IR in bone cells results in disrupted bone homeostasis during early post-natal growth. Here we have deleted IR in S100a4-lineage cells (IRcKOS100a4) and assessed the effects on bone homeostasis in both young (15 weeks) and older adult (48 weeks) mice. S100a4-Cre has previously been shown to target the perichondrium during bone development, and here we show that S100a4 is expressed by adult trabecular and cortical bone cells, and that S100a4-Cre effectively targets adult bone, resulting in efficient deletion of IRβ. Deletion of IRβ in S100a4-lineage cells does not affect initial bone acquisition or homeostasis with no changes in cortical, trabecular or mechanical properties at 15-weeks of age, relative to wild type (WT) littermates. However, by 48-weeks of age, IRcKOS100a4 mice display substantial declines in trabecular bone volume, bone volume fraction and torsional rigidity, relative to age-matched WT controls. This work establishes the utility of using S100a4-cre to target bone and demonstrates that IRβ in S100a4-lineage cells is required for maintenance of bone homeostasis in adult mice., Highlights • IRcKOS100a4 enhances age-related trabecular bone loss. • IRcKOS100a4 decreases torsional rigidity at 48 weeks of age, relative to wild type. • Cortical bone S100a4-lineage cells increase during aging. • Aging does not alter the trabecular bone S100a4-lineage population.

The functional role of Pax7-expressing satellite cells (SCs) in postnatal skeletal muscle development beyond weaning remains obscure. Therefore, the relevance of SCs during prepubertal growth, a period after weaning but prior to the onset of puberty, has not been examined. Here, we have characterized mouse skeletal muscle growth during prepuberty and found significant increases in myofiber cross-sectional area that correlated with SC-derived myonuclear number. Remarkably, genome-wide RNA-sequencing analysis established that post-weaning juvenile and early adolescent skeletal muscle have markedly different gene expression signatures. These distinctions are consistent with extensive skeletal muscle maturation during this essential, albeit brief, developmental phase. Indelible labeling of SCs with Pax7CreERT2/+; Rosa26nTnG/+ mice demonstrated SC-derived myonuclear contribution during prepuberty, with a substantial reduction at puberty onset. Prepubertal depletion of SCs in Pax7CreERT2/+; Rosa26DTA/+ mice reduced myofiber size and myonuclear number, and caused force generation deficits to a similar extent in both fast and slow-contracting muscles. Collectively, these data demonstrate SC-derived myonuclear accretion as a cellular mechanism that contributes to prepubertal hypertrophic skeletal muscle growth., Summary: Examination of gene expression and morphological changes in mouse skeletal muscle during prepuberty demonstrates that satellite cell-derived myonuclear accretion contributes to prepubertal hypertrophic skeletal muscle growth.

Category: Hindfoot Introduction/Purpose: Adult Acquired Flatfoot Deformity (AAFD) is a complex and progressive deformity characterized by abduction of the midfoot and valgus alignment of the hindfoot. Spring ligament tear is often present in advanced stages of the AAFD. Previous anatomic studies have demonstrated that the superficial deltoid ligament blends with the superomedial spring ligament to provide both medial tibiotalar and talonavicular stability aiding in coronal plane stability. Given that the spring ligament blends with the superficial deltoid ligament, we sought to investigate the kinematic effect of spring ligament tear in development of peritalar instability in cadaveric flatfoot model. We hypothesized that increased spring ligament tear size will result in increased talonavicular joint abduction (axial) and plantarflexion (sagittal), and increased valgus alignment of the tibiotalar and subtalar joints (coronal). Methods: Seven fresh-frozen cadaveric foot specimens were employed. Reflective markers were mounted on the tibia, talus, navicula, calcaneus and the first metatarsus. Kinematics of the peritalar joints were captured by multiple camera motion capture system. A flatfoot model was created by sectioning the medial and inferior talonavicular interosseous ligament, followed by cyclic axial load of 1150 N under a hydraulic loading frame with 350 N load applied to the Achilles tendon. The talo-first metatarsus (T- 1MT) abduction angle was calculated and cycles were applied until abduction of 5-10° (mild flatfoot) was achieved. Spring ligament sectioning was extended 1 cm proximally along the superomedial ligament followed by cyclic loading until 10-15° (moderate) of T- 1MT abduction was achieved. The spring ligament was sectioned for another 1 cm followed by cyclic loading until >15° (severe) abduction was noted. The relative kinematic changes were compared among the initial, mild, moderate, and severe flatfoot model using two-way ANOVA. Results: The average T-1MT abduction angles in the mild, moderate, and severe flatfoot were 7.79°+/-2.27°, 11.47°+/-2.82°, and 15.46°+4.15°. Meary’s angle increased with progression of the flatfoot (mild 6.17°+/-2.92°, moderate 9.71°+/-3.4°, severe 12.46°+/-4.13°). Hindfoot valgus angle also increased. The mild, moderate, and severe flatfoot showed 2.4°+/-3.85°, 4.13°+/-3.9°, and 4.75°+/-3.79° of tibiotalar valgus angle. The subtalar joint exhibited 2.94°+/-3.41°, 5.52°+/-4.34°, and 6.97°+/-4.83° valgus angle in the mild, moderate, and severe models. The T-1MT abduction angle and Meary’s angle were significantly different in all flatfoot models compared to the initial condition (pConclusion: Serial increment in spring ligament tear size in simulated flatfoot increased relative talus adduction and plantarflexion. It also resulted in gradual increment of valgus alignment of the tibiotalar and subtalar joints in coronal plane. This finding demonstrates that a large spring ligament tear in advanced stage AAFD leads to increased strain across the medial peritalar ligaments. In addition to osseous correction and tendon transfer, medial ligament augmentation, may be a critical component in surgical correction of AAFD with a large spring ligament tear.

Objectives: Previous studies of bony Bankart repair comparing single- and double-row reconstruction techniques have examined static forces required to displace the bony Bankart lesion. No studies, to date, have examined stability of bony Bankart repair with more physiologic concavity-compression model. We hypothesize the double-row fixation technique would provide superior stability and decreased displacement of a simulated bony Bankart lesion in a concavity-compression cadaveric model compared with single-row technique.Our aim was to examine the dynamic stability and ultimate displacement of single- vs double-row repair techniques for acute bony Bankart lesions Methods: Testing was performed on 13 matched pairs of glenoids with simulated bony Bankart fractures with a defect width of 25% of the glenoid diameter. Half of the fractures were repaired with a double-row technique, while the contralateral glenoids were repaired with a single-row technique. To determine dynamic biomechanical stability and ultimate step-off of the repairs a 150 N load and 2000 cycles of internal-external rotation at 1 Hz was applied to specimens to simulate standard rehabilitation protocols. Toggle was quantified throughout cycling with a coordinate measuring machine. After cyclic loading, the fracture displacement was measured. 3D spatial measurements were calculated using MATLAB. Results: The double-row technique resulted in significantly (p=0.005) less displacement (mean=342.48 µm SD=300.64 µm) than single-row technique (mean=981.84 µm, SD=640.38 µm). Ultimate fracture displacement of double-row repair was significantly less (mean=792.23 µm, SD=333.85 µm, p=0.046) after simulated rehabilitation by internal-external rotation cycling compared to single-row repair (mean=1,267.38 µm, SD=640.38 µm). Conclusion: The double-row fixation technique for arthroscopic bony Bankart repair results in superior stability throughout simulated rehabilitation and decreases ultimate displacement in a concavity-compression cadaveric model.

Objectives: Severe cartilage loss has been described in the setting of shallow anchor placement in arthroscopic shoulder surgery. There has been no previous investigation into the effects of cartilage loss due to suture from suture anchors overlying the repaired bony fragment. Current arthroscopic techniques for bony Bankart repair involve placement of suture overlying articular cartilage. We hypothesize there will be cartilage loss over time due to the presence of suture from suture anchors in acute bony Bankart repairs, and double-row reconstruction will cause increased humeral head cartilage loss due to an overall larger surface area when compared to single-row reconstruction. Methods: Testing was performed on 24 cadaveric glenoids, 12 right and 12 left, with simulated bony Bankart fractures with a defect width of 25% of the glenoid diameter. Half of the fractures were repaired with a double-row technique, while the contralateral glenoids were repaired with a single-row technique. Samples were randomized by blinded envelopes. Samples were subjected to 20,000 cycles of internal-external rotation across a 90o arc at 2 Hz after a compressive load of 750-N or 90% BW, whichever was less, was applied to simulate wear. Cartilage defects were quantified through a custom MATLAB script. Images were excluded for poor quality, or inadvertent tissue folding during tissue processing. Mean cartilage cutout differences were analyzed by Wilcoxon Rank Sum Test. Results: A total of 92 images were analyzed, 51 double-row and 41 single-row. The double-row technique resulted in significantly (p=0.027) more cartilage cutout (99,746.1 µm2, SD=65,864.8 µm2) than single row repair (mean=68,884.5 µm2, SD=44,373 µm2). Conclusion: Both the single-row and double-row fixation techniques resulted in damage to the humeral articular cartilage. The double-row fixation technique resulted in significantly increased chondrolysis to the humeral head after simulated wear in this cadaveric model. Despite the biomechanical superiority of double-row repair, surgeons must be aware of the increased rate of chondrolysis involved with this technique.

Category: Hindfoot Introduction/Purpose: Spring ligament tear is often present in advanced stages of the AAFD. Anatomic studies have demonstrated that the superficial deltoid ligament blends with the superomedial spring ligament to provide medial tibiotalar and talonavicular stability. Reconstruction of combined deltoid-spring ligament, or the Tibiocalcaneonvaicular ligament (TCNL) was proposed to augment medial stability in advanced AAFD with large spring ligament tears. A tendon allograft is placed to cross three peritalar (tibiotalar, talonavicular and subtalar) joints to augment medial stability. We aimed to 1) investigate the kinematic effects of TCNL reconstruction in cadaveric flatfoot model with medial ligament insufficiency, and 2) compare TCNL reconstruction with anatomic spring and anatomic deltoid ligament reconstructions (Figure 1). We hypothesized that TCNL reconstruction is effective in restoring peritalar kinematics. Methods: Five fresh-frozen cadaveric foot specimens were employed. Advanced stage flatfoot model was created by sectioning the medial and inferior talonavicular interosseous ligament and extending the release 2 cm proximally along the superomedial spring ligament. Cyclic axial load of 1150 N under a hydraulic loading frame with constant 350 N Achilles tendon load were applied until >15° talo-first metatarsal abduction was achieved. Bone tunnels were drilled for three reconstruction types, and the peroneus longus tendon was configured to reconstruct the 1) anatomic spring ligament, 2) anatomic deltoid ligament, and 3) TCNL. Reflective markers were mounted on the tibia, talus, navicula, calcaneus and first metatarsus. Each reconstruction type was loaded with 800 N ground reaction force, and kinematics of the peritalar joints were captured by 4-camera motion capture system. Forefoot abduction angle, Meary’s angle, and hindfoot valgus were calculated and compared to the severe flatfoot prior to reconstruction and to each using two-way ANOVA. Results: In creating the flatfoot deformity, both the tibiotalar and subtalar joints demonstrated an increase in valgus deformity by 5.6+3.7° and 6.1+5.3°, respectively, compared to the initial measurements. When comparing to the flatfoot deformity, the TCNL reconstruction achieved a significant improvement in percent correction of total hindfoot valgus (59.7+21.1%, p=0.017) and forefoot abduction angle (83.4+17.7%, pConclusion: In advanced stage cadaveric flatfoot with spring ligament tear, we found increased valgus alignment at both the tibiotalar and subtalar joints. This kinematic changes reflects increased strain across the medial peritalar ligaments. The deltoid-spring ligament complex (TCNL) reconstruction demonstrated significantly improved alignment of hindfoot valgus and forefoot abduction compared to the severe flatfoot condition. This finding suggests that in addition to osseous correction and tendon transfer, the TCNL reconstruction may serve as an important component in augmenting medial stability in advanced AAFD with medial ligament insufficiency.