Rotator cuff repair using a bioresorbable nanofiber interposition scaffold: a biomechanical and histologic analysis in sheep.

BACKGROUND: The purpose of this study was to evaluate the mechanical, structural, and histologic quality of rotator cuff repairs augmented with an interposition electrospun nanofiber scaffold composed of polyglycolic acid (PGA) and poly-L-lactide-co-ε-caprolactone (PLCL) in an acute sheep model. METHODS: Forty acute infraspinatus tendon detachment and repair procedures were performed in a sheep infraspinatus model using a double-row transosseous-equivalent anchor technique either with an interposition nanofiber scaffold composed of polyglycolic acid-poly-L-lactide-co-ε-caprolactone or with no scaffold. Animals were euthanized at the 6-week (20 samples) and 12-week (20 samples) postoperative time points to assess the biomechanical and histologic properties of the repairs and to compare differences within each group. RESULTS: Within the scaffold-treated group, there was a significant increase in ultimate failure force (in newtons) from 6 to 12 weeks (P < .01), a significant increase in ultimate failure load from 6 to 12 weeks (P < .01), and a significant increase in ultimate failure stress (in megapascals) from 6 to 12 weeks (P < .01). At 6 weeks, the tendon-bone attachment was most consistent with an "indirect" type of insertion, whereas at 12 weeks, a visible difference in the progression and re-formation of the enthesis was observed. Compared with controls, animals in the scaffold-treated group displayed an insertion of the fibrous tendon with the humeral footprint that was beginning to be organized in a manner similar to the "native" direct/fibrocartilaginous insertion of the ovine infraspinatus tendon. In the majority of these animals treated with the scaffold, prominent perforating collagen fibers, similar to Sharpey fibers, were present and extending through a region of calcified fibrocartilage and attaching to the humeral footprint. No surgical complications occurred in any of the 40 sheep, including delayed wound healing or infection. CONCLUSIONS: In a sheep acute rotator cuff repair model, securing a nanofiber scaffold between the tendon and the bone using a double-row transosseous-equivalent anchor fixation technique resulted in greater failure strength. Additionally, at the enthesis, Sharpey fiber-like attachments (ie, collagen fibers extending from the tendon into the calcified fibrocartilage of the humerus) were observed, which were not seen in the control group.

High bone microarchitecture, strength, and resistance to bone loss in MRL/MpJ mice correlates with activation of different signaling pathways and systemic factors.

The MRL/MpJ mice have demonstrated an enhanced tissue regeneration capacity for various tissues. In the present study, we systematically characterized bone microarchitecture and found that MRL/MpJ mice exhibit higher bone microarchitecture and strength compared to both C57BL/10J and C57BL/6J WT mice at 2, 4, and 10 months of age. The higher bone mass in MRL/MpJ mice was correlated to increased osteoblasts, decreased osteoclasts, higher cell proliferation, and bone formation, and enhanced pSMAD5 signaling earlier during postnatal development (2-month old) in the spine trabecular bone, and lower bone resorption rate at later age. Furthermore, these mice exhibit accelerated fracture healing via enhanced pSMAD5, pAKT and p-P38MAPK pathways compared to control groups. Moreover, MRL/MpJ mice demonstrated resistance to ovariectomy-induced bone loss as evidenced by maintaining higher bone volume/tissue volume (BV/TV) and lower percentage of bone loss later after ovariectomy. The consistently higher serum IGF1 level and lower RANKL level in MRL/MpJ mice may contribute to the maintenance of high bone mass in uninjured and injured bone. In conclusion, our results indicate that enhanced pSMAD5, pAKT, and p-P38MAPK signaling, higher serum IGF-1, and lower RANKL level contribute to the higher bone microarchitecture and strength, accelerated healing, and resistance to osteoporosis in MRL/MpJ mice.

A prospective study comparing tendon-to-bone interface healing using an interposition bioresorbable scaffold with a vented anchor for primary rotator cuff repair in sheep.

BACKGROUND: The purpose of this study was to evaluate the biomechanical and histologic properties of rotator cuff repairs using a vented anchor attached to a bioresorbable interpositional scaffold composed of aligned PLGA (poly(l-lactide-co-glycoside)) microfibers in an animal model compared to standard anchors in an ovine model. METHODS: Fifty-six (n = 56) skeletally mature sheep were randomly assigned to a repair of an acute infraspinatus tendon detachment using a innovative anchor-PLGA scaffold device (Treatment) or a similar anchor without the scaffold (Control). Animals were humanely euthanized at 7 and 12 weeks post repair. Histologic and biomechanical properties of the repairs were evaluated and compared. RESULTS: The Treatment group had a significantly higher fibroblast count at 7 weeks compared to the Control group. The tendon bone repair distance, percentage perpendicular fibers, new bone formation at the tendon-bone interface, and collagen type III deposition was significantly greater for the Treatment group compared with the Control group at 12 weeks (P ≤ .05). A positive correlation was identified in the Treatment group between increased failure loads at 12 weeks and the following parameters: tendon-bone integration, new bone formation, and collagen type III. No statistically significant differences in biomechanical properties were identified between Treatment and Control Groups (P > .05). CONCLUSIONS: Use of a vented anchor attached to a bioresorbable interpositional scaffold composed of aligned PLGA microfibers improves the histologic properties of rotator cuff repairs in a sheep model. Improved histology was correlated with improved final construct strength at the 12-week time point.

Biomechanical comparison of locking compression plate fixation and a novel pedicle screw external fixation to repair equine mandibular fractures.

OBJECTIVE: To determine the biomechanical properties of pedicle screw external fixation (PDW) for equine mandibular fracture repair and compare PDW to locking compression plates (LCP). STUDY DESIGN: Cadaveric study. SAMPLE POPULATION: Sixteen adult equine mandibles. METHODS: Four mandibles were kept intact, while 12 were osteotomized and stabilized with the LCP or PDW construct (6 mandibles/group). Failure, stiffness, and yield were calculated from quasi-static ramp to failure and compared with previous analysis of mandibular fracture constructs. Tooth root involvement and method of failure were determined from radiographs and videos. RESULTS: Locking compression plate constructs achieved greater stiffness and load at failure (4656 ± 577 N-m/radian, 558 ± 27 N-m P < .05) compared with PDW constructs (2626 ± 127 N-m/radian, 315 ± 48 N-m). Yield did not differ between types of fixation (369 ± 57 N-m, 193 ± 35 N-m, P = .145). Tooth involvement was noted in two LCP constructs with failure via bone fracture. Pedicle screw external fixation constructs failed via wire unraveling and screw bending. CONCLUSION: Locking compression plate fixation increased stiffness and failure of constructs but did not influence yield. It also increased the risk to tooth root involvement relative to fixation with PDW. Compared with another study, PDW offered stiffness and failure similar to an intraoral splint with interdental wires, external fixator (EF), and external fixator with wires (EFW) and yield similar to an EF, an EFW, and a dynamic compression plate. CLINICAL RELEVANCE: Pedicle screw external fixation offers biomechanical stability comparable to other relevant mandibular fixation techniques and reduces the risk of tooth root damage compared with LCP fixation.

Ex vivo comparison of intradermal closures with conventional monofilament suture vs unidirectional barbed suture in dogs.

OBJECTIVE: To evaluate the mechanical properties, strength, and quality of seal provided by continuous intradermal suture lines closed with barbed suture vs monofilament suture. STUDY DESIGN: Experimental study. SAMPLE POPULATION: Forty-eight full-thickness wounds in canine cadavers. METHODS: Four-centimeter-long parasagittal cutaneous wounds were created in canine cadavers. Each intradermal closure was closed with smooth monofilament suture and terminated with a 2 + 1 Aberdeen knot (n = 24) or a unidirectional barbed suture terminated with a single end pass (n = 24). Wounds (n = 12/group) were harvested, and a servohydraulic machine applied tensile load perpendicular to the long axis of the suture line. A load-displacement curve was generated; maximum load, displacement, stiffness, and mode of construct failure were recorded. Harvested wounds were placed in a watertight construct to measure the volume of fluid leaking over 3 minutes at 1.0 ± 0.1 psi. RESULTS: Stiffness did not differ between constructs (P > .05). Incisions closed with monofilament sutures sustained higher maximum load (311.21 N ± 87.40) and displacement at failure (21.19 mm ± 4.51) compared with those with barbed sutures (116.38 N ± 42.82 and 15.03 mm ± 2.32, respectively, P < .05). Closures with monofilament sutures leaked more (4.38 mL ± 7.90) compared with those with barbed sutures (0.15 mL ± 0.43, P < .05). CONCLUSION: Monofilament sutures resulted in stronger constructs, whereas barbed suture constructs provided a better watertight seal. CLINICAL SIGNIFICANCE: While unidirectional barbed sutures may improve watertight skin closure, surgeons should consider using conventional monofilament sutures when mechanical strength of the closure is of primary concern.

Vessel sealer and divider instrument temperature during laparoscopic ovariectomy in horses.

OBJECTIVE: To determine the temperature of a vessel sealer and divider device during unilateral paralumbar laparoscopic ovariectomy in standing, sedated mares. STUDY DESIGN: Prospective study. ANIMALS: Fifteen healthy research mares. METHODS: Healthy mares with normal ovarian palpation and ultrasonographic appearance were enrolled. Horses were restrained in standing stocks and sedated. A right or left paralumbar ovariectomy was performed with a laparoscopic portal and 2 instrument portals. Ovaries were excised with traumatic forceps and a blunt tip vessel sealer and divider. Temperatures of the vessel sealer and divider were recorded with a thermocouple device adhered to the tip of the instrument. Variables were reported as median and interquartile range (IQR). RESULTS: Surgical time was 30 minutes (IQR, 25-32) including use of the vessel sealer and the divider for 4.1 minutes (IQR, 3.2-5.8). The tip of the instrument reached temperatures of 77°C (IQR, 72-85) during activation and 64°C (IQR, 61-67) at end cycle. The median increase in end-cycle instrument tip temperature per activation cycle was 2°C (IQR, -1-6). All mares returned to their intended use. CONCLUSION: Despite the instrument temperatures observed during unilateral laparoscopic ovariectomy, surgical complications were minimal. The clinical relevance of the increase in instrument tip temperature of the vessel sealer and divider is presently unclear, but surgeons should use the instrument with caution, especially in close proximity to viscera. The increase in temperature observed at the tip of the vessel sealer and divider during unilateral ovariectomy could be associated with morbidity. The clinical relevance of instrument tip heating during other procedures, such as adhesiolysis and intestinal resection, is unknown and should be evaluated.

Comparison of Micro-Computed Tomography and Digital Intraoral Radiography to Determine the Accuracy of Digital Radiographic Measurements of Mandibular Molar Teeth in Dogs.

INTRODUCTION: The purpose of this study was to compare root and root canal width measurements between digital intraoral radiography (IOR) and micro-computed tomography (µCT). The accuracy of IOR measurements of canine mandibular molars was scrutinized to assess feasibility of developing a model to estimate animal age based on dentinal thickness. MATERIALS AND METHODS: Thirty-nine canine mandibular first molars were imaged using µCT and IOR. For each tooth, the root and root canal width of the mesial and distal roots were measured by a single observer at 3 marked sites on µCT and IOR. Two different software programs were used to measure the radiographs. The radiograph measurements were compared to each other and to the µCT measurements. The µCT images were considered the anatomic reference standard for structural representation. RESULTS: The data collected demonstrated IOR bias and variability throughout all measurement sites, with some sites being more affected than others. Neither IOR system produced unbiased measurements that closely reflected the µCT measurements consistently. The overall lack of agreement between measurements demonstrated the difficulties in developing a standardized protocol for measuring root and root canal width for the first molar teeth in dogs. CONCLUSION: Developing a protocol to accurately measure and compare µCT and IOR measurements is challenging. Designing a measurement system that would allow for universal application to age dogs would require continued research utilizing a standardized approach to overcome the limitations identified in this article.

An in vivo ovine model of bone tissue alterations in simulated microgravity conditions.

Microgravity and its inherent reduction in body-weight associated mechanical loading encountered during spaceflight have been shown to produce deleterious effects on important human physiological processes. Rodent hindlimb unloading is the most widely-used ground-based microgravity model. Unfortunately, results from these studies are difficult to translate to the human condition due to major anatomic and physiologic differences between the two species such as bone microarchitecture and healing rates. The use of translatable ovine models to investigate orthopedic-related conditions has become increasingly popular due to similarities in size and skeletal architecture of the two species. Thus, a new translational model of simulated microgravity was developed using common external fixation techniques to shield the metatarsal bone of the ovine hindlimb during normal daily activity over an 8 week period. Bone mineral density, quantified via dual-energy X-ray absorptiometry, decreased 29.0% (p < 0.001) in the treated metatarsi. Post-sacrifice biomechanical evaluation revealed reduced bending modulus (-25.8%, p < 0.05) and failure load (-27.8%, p < 0.001) following the microgravity treatment. Microcomputed tomography and histology revealed reduced bone volume (-35.9%, p < 0.01), trabecular thickness (-30.9%, p < 0.01), trabecular number (-22.5%, p < 0.05), bone formation rate (-57.7%, p < 0.01), and osteoblast number (-52.5%, p < 0.001), as well as increased osteoclast number (269.1%, p < 0.001) in the treated metatarsi of the microgravity group. No significant alterations occurred for any outcome parameter in the Sham Surgery Group. These data indicate that the external fixation technique utilized in this model was able to effectively unload the metatarsus and induce significant radiographic, biomechanical, and histomorphometric alterations that are known to be induced by spaceflight. Further, these findings demonstrate that the physiologic mechanisms driving bone remodeling in sheep and humans during prolonged periods of unloading (specifically increased osteoclast activity) are more similar than previously utilized models, allowing more comprehensive investigations of microgravity-related bone remodeling as it relates to human spaceflight.

Exosome Cell Origin Affects In Vitro Markers of Tendon Repair in Ovine Macrophages and Tenocytes.

Tendon injuries and disease are resistant to surgical repair; thus, adjunct therapies are widely investigated, especially mesenchymal stromal cells (MSCs) and, more recently, their extracellular vesicles (MSCdEVs), for example, exosomes. Thought to act on resident and infiltrating immune cells, the role of MSCdEVs in paracrine signaling is of great interest. This study investigated how MSCdEVs differ from analogs derived from resident (tenocyte) populations (TdEV). As macrophages play a significant role in tendon maintenance and repair, macrophage signaling was compared by cytokine quantification using a multiplexed immunoassay and tenocyte migration by in vitro scratch-wound analysis. TdEV-treated macrophages decreased IL-1 and increased MIP-1 and CXCL8 expression. In addition, macrophage signaling favored collagen synthesis and tenocyte bioactivity, while reducing proangiogenic signaling when TdEVs were used in place of MSCdEVs. These in vitro data demonstrate a differential influence of exosomes on macrophage signaling, according to cell source, supporting that local cell-derived exosomes may preferentially drive healing by different means with possible different outcomes compared to MSCdEVs. Impact Statement Adipose-derived mesenchymal stromal cell (AdMSC) exosomes (EVs) can improve tendon mechanical resilience, tissue organization, and M2 macrophage phenotype predominance in response to tendon injury. This active area of investigation drives great interest in the function of these exosomes as adjunct therapies for tendon disease, particularly rotator cuff tendinopathy. However, little is known about the effects of EVs as a function of cell source, nor regarding their efficacy in preclinical translational ovine models. Herein we demonstrate a differential effect of exosomes as a function of cell source, tenocyte compared to AdMSCs, on macrophage signaling and tenocyte migration of ovine cells.

Biomechanical and histological changes secondary to aging in the human rotator cuff: A preliminary analysis.

The high failure rate of rotator cuff repair surgeries is positively correlated with age, yet the biomechanical changes to the tendons of the rotator cuff with age have not been described. As such, we sought to benchmark and characterize the biomechanical and histopathological properties with the accompanying gene expression of human rotator cuff tendons as a function of age and histopathological degeneration. All four rotator cuff tendons from fresh human cadaver shoulders underwent biomechanical, histopathological, and gene expression analyses. Following cadaver availability, samples were grouped into Younger (i.e., less than 36 years of age, n = 2 donors) and Aged (i.e., greater than 55 years of age, n = 3 donors) as a means of characterizing and quantifying the age-related changes exhibited by the tendons. Biomechanical testing and subsequent computational modeling techniques revealed both differences in properties between tendons and greater Young's moduli in the Younger tendons (supraspinatus 3.06x, infraspinatus 1.76x, subscapularis 1.25x, and teres minor 1.32x). Histopathological scoring using the semi-quantitative Bonar scoring scheme revealed a positive correlation with age across all tendons (r = 0.508, p < 0.001). These data contextualize the biomechanical and histopathological changes to tendons that occurs naturally with aging, highlighting the innate differences in biomechanical properties of all four rotator cuff tendons, as well as the difference in their degenerative trajectories. Additionally, the histopathological scoring revealed moderate signs of degeneration within the Younger supraspinatus tendons, suggesting tissue quality may decrease in this specific tendon in patients less than 40 years old, before clinical symptoms or tears.

Employing direct electromagnetic coupling to assess acute fracture healing: An ovine model assessment.

OBJECTIVES: This study explored the efficacy of collecting temporal fracture site compliance data via an advanced direct electromagnetic coupling (DEC) system equipped with a Vivaldi-type antenna, novel calibration technique, and multi-antenna setup (termed maDEC) as an approach to monitor acute fracture healing progress in a translational large animal model. The overarching goal of this approach was to provide insights into the acute healing dynamics, offering a promising avenue for optimizing fracture management strategies. METHODS: A sample of twelve sheep, subjected to ostectomies and intramedullary nail fixations, was divided into two groups, simulating normal and impaired healing scenarios. Sequential maDEC compliance or stiffness measurements and radiographs were taken from the surgery until euthanasia at four or eight weeks and were subsequently compared with post-sacrifice biomechanical, micro-CT, and histological findings. RESULTS: The results showed that the maDEC system offered straightforward quantification of fracture site compliance via a multiantenna array. Notably, the rate of change in the maDEC-measured bending stiffness significantly varied between normal and impaired healing groups during both the 4-week (p = 0.04) and 8-week (p = 0.02) periods. In contrast, radiographically derived mRUST healing measurements displayed no significant differences between the groups (p = 0.46). Moreover, the cumulative normalized stiffness maDEC data significantly correlated with post-sacrifice mechanical strength (r2 = 0.80, p < 0.001), micro-CT measurements of bone volume fraction (r2 = 0.60, p = 0.003), and density (r2 = 0.60, p = 0.003), and histomorphometric measurements of new bone area fraction (r2 = 0.61, p = 0.003) and new bone area (r2 = 0.60, p < 0.001). CONCLUSIONS: These data indicate that the enhanced maDEC system provides a non-invasive, accurate method to monitor fracture healing during the acute healing phase, showing distinct stiffness profiles between normal and impaired healing groups and offering critical insights into the healing process's progress and efficiency.

Enhanced bone formation in locally-optimised, low-stiffness additive manufactured titanium implants: An in silico and in vivo tibial advancement study.

A tibial tuberosity advancement (TTA), used to treat lameness in the canine stifle, provides a framework to investigate implant performance within an uneven loading environment due to the dominating patellar tendon. The purpose of this study was to reassess how we design orthopaedic implants in a load-bearing model to investigate potential for improved osseointegration capacity of fully-scaffolded mechanically-matched additive manufactured (AM) implants. While the mechanobiological nature of bone is well known, we have identified a lower limit in the literature where investigation into exceedingly soft scaffolds relative to trabecular bone ceases due to the trade-off in mechanical strength. We developed a finite element model of the sheep stifle to assess the stresses and strains of homogeneous and locally-optimised TTA implant designs. Using additive manufacturing, we printed three different low-stiffness Ti-6Al-4 V TTA implants: 0.8 GPa (Ti1), 0.6 GPa (Ti2) and an optimised design with a 0.3 GPa cortex and 0.1 GPa centre (Ti3), for implantation in a 12-week in vivo ovine pilot study. Static histomorphometry demonstrated uniform bone ingrowth in optimised low-modulus Ti3 samples compared to homogeneous designs (Ti1 and Ti2), and greater bone-implant contact. Mineralising surfaces were apparent in all implants, though mineral apposition rate was only consistent throughout Ti3. The greatest bone formation scores were seen in Ti3, followed by Ti2 and Ti1. Results from our study suggest lower stiffnesses and higher strain ranges improve early bone formation, and that by accounting for loading environments through rational design, implants can be optimised to improve uniform osseointegration. STATEMENT OF SIGNIFICANCE: The effect of different strain ranges on bone healing has been traditionally investigated and characterised through computational models, with much of the literature suggesting higher strain ranges being favourable. However, little has been done to incorporate strain-optimisation into porous orthopaedic implants due to the trade-off in mechanical strength required to induce these microenvironments. In this study, we used finite element analysis to optimise the design of additive manufactured (AM) titanium orthopaedic implants for different strain ranges, using a clinically-relevant surgical model. Our research suggests that there is potential for locally-optimised AM scaffolds in the use of orthopaedic devices to induce higher strains, which in turn encourages de novo bone formation and uniform osseointegration.

Preclinical tendon and ligament models: Beyond the 3Rs (replacement, reduction, and refinement) to 5W1H (why, who, what, where, when, how).

Several tendon and ligament animal models were presented at the 2022 Orthopaedic Research Society Tendon Section Conference held at the University of Pennsylvania, May 5 to 7, 2022. A key objective of the breakout sessions at this meeting was to develop guidelines for the field, including for preclinical tendon and ligament animal models. This review summarizes the perspectives of experts for eight surgical small and large animal models of rotator cuff tear, flexor tendon transection, anterior cruciate ligament tear, and Achilles tendon injury using the framework: "Why, Who, What, Where, When, and How" (5W1H). A notable conclusion is that the perfect tendon model does not exist; there is no single gold standard animal model that represents the totality of tendon and ligament disease. Each model has advantages and disadvantages and should be carefully considered in light of the specific research question. There are also circumstances when an animal model is not the best approach. The wide variety of tendon and ligament pathologies necessitates choices between small and large animal models, different anatomic sites, and a range of factors associated with each model during the planning phase. Attendees agreed on some guiding principles including: providing clear justification for the model selected, providing animal model details at publication, encouraging sharing of protocols and expertise, improving training of research personnel, and considering greater collaboration with veterinarians. A clear path for translating from animal models to clinical practice was also considered as a critical next step for accelerating progress in the tendon and ligament field.

Effect of sequential removal of parts of the second metacarpal bone on the biomechanical stability of the equine carpus.

OBJECTIVE: To quantify changes in biomechanical stability and stiffness within the equine carpus after removal of 50%, 80%, and 100% of the second metacarpal bone (MC2). STUDY DESIGN: In vitro biomechanical study. METHODS: Cadaveric equine forelimbs (n = 16) were evaluated. Intact constructs were loaded in axial compression from 0 to 5000 N and compression + torsion (5000 N ± 20°) for 5 cycles. This was repeated after removal of 50%, 80%, and 100% of MC2. The primary biomechanical outcome variables were the compressive stiffness and compressive + torsional stiffness of the carpus. Relative kinematic motion was also evaluated between the second carpal bone (C2) and the radial carpal bone (RC), C2 and the third metacarpal bone (MC3) and C2 and the third carpal bone (C3). RESULTS: A significant decrease in compressive + torsional stiffness was found after 100% removal of MC2. Compressive stiffness of the carpus did not change after 100% MC2 removal. A significant increase in relative rotation around the z-axis (rotation around the long axis) was observed for C2 versus MC3 and C2 versus C3 when 100% of MC2 was removed as compared to 80%, 50%, and 0% removal. No significant difference in relative rotation between C2 and RC was detected. CONCLUSIONS: The biomechanical results reported here suggest that the torsional stability of the equine carpus is significantly decreased only after complete resection of MC2.

Vivaldi Antennas for Contactless Sensing of Implant Deflections and Stiffness for Orthopaedic Applications.

The implementation of novel coaxial dipole antennas has been shown to be a satisfactory diagnostic platform for the prediction of orthopaedic bone fracture healing outcomes. These techniques require mechanical deflection of implanted metallic hardware (i.e., rods and plates), which, when loaded, produce measurable changes in the resonant frequency of the adjacent antenna. Despite promising initial results, the coiled coaxial antenna design is limited by large antenna sizes and nonlinearity in the resonant frequency data. The purpose of this study was to develop two Vivaldi antennas (a.k.a., "standard" and "miniaturized") to address these challenges. Antenna behaviors were first computationally modeled prior to prototype fabrication. In subsequent benchtop tests, metallic plate segments were displaced from the prototype antennas via precision linear actuator while measuring resultant change in resonant frequency. Close agreement was observed between computational and benchtop results, where antennas were highly sensitive to small displacements of the metallic hardware, with sensitivity decreasing nonlinearly with increasing distance. Greater sensitivity was observed for the miniaturized design for both stainless steel and titanium implants. Additionally, these data demonstrated that by taking resonant frequency data during implant displacement and then again during antenna displacement from the same sample, via linear actuators, that "antenna calibration procedures" could be used to enable a clinically relevant quantification of fracture stiffness from the raw resonant frequency data. These improvements mitigate diagnostic challenges associated with nonlinear resonant frequency response seen in previous antenna designs.

Modified Alendronate Mitigates Mechanical Degradation of the Rotator Cuff in an Osteoporotic Ovine Model.

BACKGROUND: Osteoporosis is an independent risk factor for failure after arthroscopic rotator cuff repair. Since rerupture rates after rotator cuff repair are associated with decreased bone mineral density and bone microarchitecture, adaptations of biomechanical properties of the rotator cuff enthesis in patients with osteoporosis remain unclear. Additionally, the effects of osteogenic therapy carrier drugs used for the treatment of osteoporosis on rotator cuff structure and properties have not been previously documented. PURPOSE: To investigate the changes to soft tissue biomechanics and insertional structure secondary to osteoporosis with and without an osteogenic therapy carrier (ie, modified alendronate). STUDY DESIGN: Controlled laboratory study. METHODS: Biomechanical, histopathological, and microcomputed tomography analyses were performed on 20 shoulders obtained from 10 osteoporotic sheep randomly allocated to modified bisphosphonate (ie, alendronate) or control (ie, osteoporotic without treatment) groups; 6 shoulders from healthy sheep were utilized for comparison purposes. RESULTS: Tendons from the control group exhibited a 57% decrease in undeformed Young modulus as compared with the healthy group (P = .010). Tendons from the modified bisphosphonate treatment group exhibited a 229% increase in initial Young modulus as compared with the control group (P = .010). Marked changes within the tendon insertional organization were noted in both the control and the modified bisphosphonate treatment group samples as evidenced by increased interdigitation of the bone-mineralized fibrocartilaginous junction. The control samples exhibited a markedly paucicellular insertion, whereas the modified bisphosphonate treated tendons exhibited a hypercellular insertional region as compared with the healthy group. Both groups exhibited significantly (P < .01) decreased bone quality underlying the infraspinatus insertion, as evidenced by all microcomputed tomography outcome parameters. CONCLUSION: This work illuminates changes to rotator cuff tendon secondary to osteoporosis. Specifically, it revealed decreased tendon modulus and altered insertional structure in the osteoporotic samples. Secondarily, these data revealed increases in tendon modulus accompanied by increased cellularity within the tendon insertion region after systemic modified bisphosphonate injections. CLINICAL RELEVANCE: Bisphosphonate treatment may have a positive effect on the healing of the enthesis after rotator cuff repair.

Direct electromagnetic coupling to determine diagnostic bone fracture stiffness.

Background: Rapid prediction of adverse bone fracture healing outcome (e.g., nonunion and/or delayed union) is essential to advise adjunct therapies to reduce patient suffering and improving healing outcome. Radiographic diagnostic methods remain ineffective during early healing, resulting in average nonunion diagnosis times surpassing six months. To address this clinical deficit, we developed a novel diagnostic device to predict fracture healing outcome by noninvasive telemetric measurements of fracture bending stiffness. This study evaluated the hypothesis that our diagnostic antenna system is capable of accurately measuring temporal fracture healing stiffness, and advises the utility of this data for expedited prediction of healing outcomes during early (≤3 weeks) fracture recovery. Methods: Fracture repair was simulated, in reverse chronology, by progressively destabilizing cadaveric ovine metatarsals (n=8) stabilized via locking plate fixation. Bending stiffness of each fracture state were predicted using a novel direct electromagnetic coupling diagnostic system, and results were compared to values from material testing (MT) methods. While direct calculation of fracture stiffness in a simplistic cadaver model is possible, comparable analysis of the innumerable permutations of fracture and treatment type is not feasible. Thus, clinical feasibility of direct electromagnetic coupling was explored by parametric finite element (FE) analyses (n=1,632 simulations). Implant mechanics were simulated throughout the course of healing for cases with variations to fracture size, implant type, implant structure, and implant material. Results: For all fracture states, stiffness values predicted by the direct electromagnetic coupling system were not significantly different than those quantified by in vitro MT methods [P=0.587, P=0.985, P=0.975; for comparing intact, destabilized, and fully fractured (FF) states; respectively]. In comparable models, the total implant deflection reduction (from FF to intact states) was less than 10% different between direct electromagnetic coupling measurements (82.2 µm) and FE predictions (74.7 µm). For all treatment parameters, FE analyses predicted nonlinear reduction in bending induced implant midspan deflections for increasing callus stiffness. Conclusions: This technology demonstrates potential as a noninvasive clinical tool to accurately quantify healing fracture stiffness to augment and expedite healing outcome predictions made using radiographic imaging.

Multiscale Contrasts Between the Right and Left Ventricle Biomechanics in Healthy Adult Sheep and Translational Implications.

Cardiac biomechanics play a significant role in the progression of structural heart diseases (SHDs). SHDs alter baseline myocardial biomechanics leading to single or bi-ventricular dysfunction. But therapies for left ventricle (LV) failure patients do not always work well for right ventricle (RV) failure patients. This is partly because the basic knowledge of baseline contrasts between the RV and LV biomechanics remains elusive with limited discrepant findings. The aim of the study was to investigate the multiscale contrasts between LV and RV biomechanics in large animal species. We hypothesize that the adult healthy LV and RV have distinct passive anisotropic biomechanical properties. Ex vivo biaxial tests were performed in fresh sheep hearts. Histology and immunohistochemistry were performed to measure tissue collagen. The experimental data were then fitted to a Fung type model and a structurally informed model, separately. We found that the LV was stiffer in the longitudinal (outflow tract) than circumferential direction, whereas the RV showed the opposite anisotropic behavior. The anisotropic parameter K from the Fung type model accurately captured contrasting anisotropic behaviors in the LV and RV. When comparing the elasticity in the same direction, the LV was stiffer than the RV longitudinally and the RV was stiffer than the LV circumferentially, suggesting different filling patterns of these ventricles during diastole. Results from the structurally informed model suggest potentially stiffer collagen fibers in the LV than RV, demanding further investigation. Finally, type III collagen content was correlated with the low-strain elastic moduli in both ventricles. In summary, our findings provide fundamental biomechanical differences between the chambers. These results provide valuable insights for guiding cardiac tissue engineering and regenerative studies to implement chamber-specific matrix mechanics, which is particularly critical for identifying biomechanical mechanisms of diseases or mechanical regulation of therapeutic responses. In addition, our results serve as a benchmark for image-based inverse modeling technologies to non-invasively estimate myocardial properties in the RV and LV.

Biomechanical, Morphological, and Biochemical Characteristics of Articular Cartilage of the Ovine Humeral Head.

OBJECTIVE: Shoulder pain is commonly attributed to rotator cuff injury or osteoarthritis. Ovine translational models are used to investigate novel treatments aimed at remedying these conditions to prevent articular cartilage degeneration and subsequent joint degradation. However, topographical properties of articular cartilage in the ovine shoulder are undefined. This study investigates the biomechanical, morphological, and biochemical attributes of healthy ovine humeral head articular cartilage and characterizes topographical variations between surface locations. DESIGN: Ten humeral heads were collected from healthy skeletally mature sheep and each was segregated into 4 quadrants using 16 regions of interest (ROIs) across the articular surface. Articular cartilage of each ROI was analyzed for creep indentation, thickness, and sulfated glycosaminoglycan (sGAG) and collagen quantity. Comparisons of each variable were made between quadrants and between ROIs within each quadrant. RESULTS: Percent creep, thickness, and sGAG content, but not collagen content, were significantly different between humeral head quadrants. Subregion analysis of the ROIs within each surface quadrant revealed differences in all measured variables within at least one quadrant. Percent creep was correlated with sGAG (r = -0.32, P = 0.0001). Collagen content was correlated with percent creep (r = 0.32, P = 0.0009), sGAG (r = -0.19, P = 0.049), and thickness (r = -0.19, P = 0.04). CONCLUSIONS: Topographical variations exist in mechanical, morphologic, and biochemical properties across the articular surface of the ovine humeral head. Recognizing this variability in ovine humeral head cartilage will provide researchers and clinicians with accurate information that could impact study outcomes.

A Large Animal Model for Orthopedic Foot and Ankle Research.

Trauma to the soft tissues of the ankle joint distal syndesmosis often leads to syndesmotic instability, resulting in undesired movement of the talus, abnormal pressure distributions, and ultimately arthritis if deterioration progresses without treatment. Historically, syndesmotic injuries have been repaired by placing a screw across the distal syndesmosis to provide rigid fixation to facilitate ligament repair. While rigid syndesmotic screw fixation immobilizes the ligamentous injury between the tibia and fibula to promote healing, the same screws inhibit normal physiologic movement and dorsiflexion. It has been shown that intact screw removal can be beneficial for long-term patient success; however, the exact timing remains an unanswered question that necessitates further investigation, perhaps using animal models. Because of the sparsity of relevant preclinical models, the purpose of this study was to develop a new, more translatable, large animal model that can be used for the investigation of clinical foot and ankle implants. Eight (8) skeletally mature sheep underwent stabilization of the left and right distal carpal bones following transection of the dorsal and interosseous ligaments while the remaining two animals served as un-instrumented controls. Four of the surgically stabilized animals were sacrificed 6 weeks after surgery while the remaining four animals were sacrificed 10 weeks after surgery. Ligamentous healing was evaluated using radiography, histology, histomorphometry, and histopathology. Overall, animals demonstrated a high tolerance to the surgical procedure with minimal complications. Animals sacrificed at 10 weeks post-surgery had a slight trend toward mildly decreased inflammation, decreased necrotic debris, and a slight increase in the healing of the transected ligaments. The overall degree of soft tissue fibrosis/fibrous expansion, including along the dorsal periosteal surfaces/joint capsule of the carpal bones was very similar between both timepoints and often exhibited signs of healing. The findings of this study indicate that the carpometacarpal joint may serve as a viable location for the investigation of human foot and ankle orthopedic devices. Future work may include the investigation of orthopedic foot and ankle medical devices, biologic treatments, and repair techniques in a large animal model capable of providing translational results for human treatment.