Robot and ultrasound assisted needle insertion to the transverse carpal ligament.

BACKGROUND: A potential alternative treatment to surgery for carpal tunnel syndrome is to inject enzymes into the transverse carpal ligament to decrease its stiffness and alleviate pressure off the median nerve. An accurate injection is needed for delivery to achieve the effects of tissue degradation. The purposes of this study were to 1) determine injection sites using 3D reconstructed anatomy, and 2) insert the needle to the middle of the transverse carpal ligament thickness in situ. METHODS: Six fresh-frozen cadaveric hands were used in this study. Five injection sites were determined in the sagittal plane along the center of the transverse carpal ligament thickness ulnar to the thenar muscle attachment using 3D ultrasonographic reconstruction. Each injection was delivered by rigidly fixing a 27-gauge needle to a six degrees of freedom robot arm programmed to insert the needle tip to the intended target. Ultrasound images were taken of the needle after insertion to measure accuracy and precision of the needle placement. FINDINGS: The needle tip was successfully delivered to the middle region of the transverse carpal ligament thickness and visualized using ultrasound imaging. The accuracy and precision of the needle insertion were 0.83 and 0.31 mm, respectively. INTERPRETATION: Methodology was established for robot-assisted needle insertion to the transverse carpal ligament using 3D ultrasonographic reconstructed anatomy. This methodology can be used in the future to deliver enzymatic injections to the transverse carpal ligament as a potential treatment for carpal tunnel syndrome.

Morphine-induced osteolysis and hypersensitivity is mediated through toll-like receptor-4 in a murine model of metastatic breast cancer.

ABSTRACT: The propensity for breast cancer to metastasize to bone is coupled to the most common complaint among breast cancer patients: bone pain. Classically, this type of pain is treated using escalating doses of opioids, which lack long-term efficacy due to analgesic tolerance, opioid-induced hypersensitivity, and have recently been linked to enhanced bone loss. To date, the molecular mechanisms underlying these adverse effects have not been fully explored. Using an immunocompetent murine model of metastatic breast cancer, we demonstrated that sustained morphine infusion induced a significant increase in osteolysis and hypersensitivity within the ipsilateral femur through the activation of toll-like receptor-4 (TLR4). Pharmacological blockade with TAK242 (resatorvid) as well as the use of a TLR4 genetic knockout ameliorated the chronic morphine-induced osteolysis and hypersensitivity. Genetic MOR knockout did not mitigate chronic morphine hypersensitivity or bone loss. In vitro studies using RAW264.7 murine macrophages precursor cells demonstrated morphine-enhanced osteoclastogenesis that was inhibited by the TLR4 antagonist. Together, these data indicate that morphine induces osteolysis and hypersensitivity that are mediated, in part, through a TLR4 receptor mechanism.

Dose- and time-dependent effects of collagenase clostridium histolyticum injection on transverse carpal ligament elastic modulus and thickness in vitro.

A potential treatment for carpal tunnel syndrome is to biochemically alter the mechanical properties of the transverse carpal ligament (TCL) through Collagenase Clostridium Histolyticum (CCH) injection. The purpose of this study was to determine the time- and dose-dependent effects of CCH injection on TCL elastic modulus and thickness. Nine TCLs were dissected from cadaveric hands for this study. CCH doses of 50U, 100U, 150U, 200U, and 250U were injected into five points on the TCL, respectively. B-mode and shear wave elastography images were taken of each injection point using robot-assisted ultrasound imaging immediately after injection, as well as 2, 4, 6, 8, and 24 hours after injection. TCL thickness and mean shear wave speed were measured for each CCH dose at each time point. CCH doses of 200U and 250U decreased shear wave speed by 18.70% and 30.01% (p<0.05), respectively, after 24 hours. CCH doses of 150U, 200U, and 250U decreased TCL thickness by 7.28%, 10.97%, and 14.92%, respectively, after 24 hours (p<0.05). Our findings suggest that CCH injection may be effective in degrading TCL tissue, with higher doses of CCH resulting in greater tissue degradation up to 24 hours after injection.

A Large Segmental Mid-Diaphyseal Femoral Defect Sheep Model: Surgical Technique.

Background:There are numerous animal models available to study bone healing as well as test strategies to accelerate bone formation. Sheep are commonly used for evaluation of long bone fractures due to similar dimensions and weight bearing environments compared to patients. Large critical-size defects can be created in sheep to facilitate the study of implantable materials, osteogenic proteins, and stem cell treatments. Studies have been published using plates to stabilize large critical size defects in femoral, tibial, and metatarsal defects. External fixators have also been used to stabilize tibial defects in sheep.Methods: The purpose of the current paper is to detail the surgical technique for creation of a 42 mm mid-diaphyseal femoral defect stabilization with an intramedullary device in sheep. Additional surgical details are provided for dynamization, reverse dynamization, and device removal.Conclusion: The article provides multiple technical tips applicable to this and other ovine osteotomy models and concludes with a discussion comparing the use of each stabilization technique in clinically significant large critical-size bone defects.

Osseosurface electronics-thin, wireless, battery-free and multimodal musculoskeletal biointerfaces.

Bioelectronic interfaces have been extensively investigated in recent years and advances in technology derived from these tools, such as soft and ultrathin sensors, now offer the opportunity to interface with parts of the body that were largely unexplored due to the lack of suitable tools. The musculoskeletal system is an understudied area where these new technologies can result in advanced capabilities. Bones as a sensor and stimulation location offer tremendous advantages for chronic biointerfaces because devices can be permanently bonded and provide stable optical, electromagnetic, and mechanical impedance over the course of years. Here we introduce a new class of wireless battery-free devices, named osseosurface electronics, which feature soft mechanics, ultra-thin form factor and miniaturized multimodal biointerfaces comprised of sensors and optoelectronics directly adhered to the surface of the bone. Potential of this fully implanted device class is demonstrated via real-time recording of bone strain, millikelvin resolution thermography and delivery of optical stimulation in freely-moving small animal models. Battery-free device architecture, direct growth to the bone via surface engineered calcium phosphate ceramic particles, demonstration of operation in deep tissue in large animal models and readout with a smartphone highlight suitable characteristics for exploratory research and utility as a diagnostic and therapeutic platform.

Sensate scaffolds coupled to telemetry can monitor in vivo loading from within a joint over extended periods of time.

Polymer scaffolds have been used as a tool to provide growth and integration of engineered tissue substrates to repair damaged tissues in many organ systems including articular cartilage. Previous work has shown that "sensate" scaffolds, with integrated strain gauges have the potential for use as both a delivery vehicle for engineered cartilage as well as a device that can measure real time, in vivo joint loading. The purpose of this study was to use an implanted subminiature telemetry system to collect in vivo joint loading measurements over an extended period following placement of a "sensate" scaffold. Measurements were collected from seven of nine sensors that were implanted into the stifles of three canines. The limb loading rates and load distribution through gait were dependent on stride time but did not vary with time post op. The peak loads were not dependent on stride time but significantly increased with time post op. This demonstrated that peak loading measured with "sensate" scaffolds can be used to monitor healing. The portability of the "sensate" scaffolds coupled to telemetry systems highlights the potential use of this system in a clinical research setting to gather important information to improve tissue engineering and rehabilitation regimens.

Functionally improved bone in calbindin-D28k knockout mice.

In vitro studies indicate that Calbindin-D28k, a calcium binding protein, is important in regulating the life span of osteoblasts as well as the mineralization of bone extracellular matrix. The recent creation of a Calbindin-D28k knockout mouse has provided the opportunity to study the physiological effects of the Calbindin-D28k protein on bone remodeling in vivo. In this experiment, histomorphometry, microCT, and bend testing were used to characterize bones in Calbindin-D28k KO (knockout) mice. The femora of Calbindin-D28k KO mice had significantly increased cortical bone volume (60.4% +/- 3.1) compared to wild-type (WT) mice (45.4% +/- 4.6). The increased bone volume was due to a decrease in marrow cavity area, and significantly decreased endosteal perimeters (3.397 mm +/- 0.278 in Calbindin-D28k KO mice, and 4.046 mm +/- 0.450 in WT mice). Similar changes were noted in the analysis of the tibias in both mice. The bone formation rates were similar in the femoral and tibial cortical bones of both mice. microCT analysis of the trabecular bone in the tibial plateau indicated that Calbindin-D28k KO mice had an increased bone volume (35.2% +/- 3.1) compared to WT mice (24.7% +/- 4.9) which was primarily due to increased trabecular number (8.99 mm(-1) +/- 0.94 in Calbindin-D28k KO mice compared to 6.75 mm(-1) +/- 0.85 in WT mice). Bone mineral content analysis of the tibias indicated that there is no difference in the calcium or phosphorus content between the Calbindin-D28k KO and WT mice. Cantilever bend testing of the femora demonstrated significantly lower strains in the bones of Calbindin-D28k KO mice (4135 micro strain/kg +/- 1266) compared to WT mice (6973 micro strain/kg +/- 998) indicating that the KO mice had stiffer bones. Three-point bending demonstrated increased failure loads in bones of Calbindin-D28k KO mice (31.6 N +/- 2.1) compared to WT mice (15.0 N +/- 1.7). In conclusion, Calbindin-D28k KO mice had increased bone volume and stiffness indicating that Calbindin-D28k plays an important role in bone remodeling.

In vivo strain measurements from hardware and lamina during spine fusion.

Currently, spine fusion is determined using radiography and clinical evaluation. There are discrepancies between radiographic evidence and direct measurements of fusion, such as operative exploration and biomechanical or histological measurements. In order to facilitate the rapid return of patients to normal activities, a monitoring technique to accurately detect fusion in vivo and to prevent overload during the postoperative period would be useful. The objectives of this study were to develop an implantable monitoring system consisting of CPC-coated strain gauges and a radio transmitter to detect the onset of fusion and measure strain during postsurgical activities. A patient underwent anterior release and fusion, followed by posterior instrumentation and fusion with segmental spinal instrumentation. Four strain gauges were placed during surgery. One was attached to the left-side rod and one to each of the lamina at T9, T10, and T11. An externally powered implanted radio transmitter attached to the gauges was placed in a subcutaneous pouch. Strains were monitored weekly and tabulated during various activities for 7 months. Peak strains during twisting and bending were tabulated to detect the onset of fusion. Strains were also recorded during activities such as climbing off an examination table, rising from a chair, and climbing stairs. Strains collected from the left rod indicated that, immediately postoperatively, it was loaded at acceptable levels. The largest and most consistent strain changes measured from the lamina were recorded during twisting.

Brachial Plexopathy Following Use of Recombinant Human BMP-2 for Treatment of Atrophic Delayed Union of the Clavicle.

CASE: Although recombinant human bone morphogenetic protein-2 (rhBMP-2) is approved for treatment of open tibial fractures and anterior lumbar interbody fusion, off-label use has been associated with complications such as local inflammation, osteolysis, and dysphagia. This case report describes a patient treated with rhBMP-2 for an atrophic delayed union of a clavicular fracture who subsequently developed a profound motor and sensory brachial plexopathy. CONCLUSION: Use of rhBMP-2 near peripheral nerves may cause neuropathy. This should be considered prior to its use in surgical sites with peripheral nerves in proximity.

Evidence-based Comprehensive Approach to Forearm Arterial Laceration.

INTRODUCTION: Penetrating injury to the forearm may cause an isolated radial or ulnar artery injury, or a complex injury involving other structures including veins, tendons and nerves. The management of forearm laceration with arterial injury involves both operative and nonoperative strategies. An evolution in management has emerged especially at urban trauma centers, where the multidisciplinary resource of trauma and hand subspecialties may invoke controversy pertaining to the optimal management of such injuries. The objective of this review was to provide an evidence-based, systematic, operative and nonoperative approach to the management of isolated and complex forearm lacerations. A comprehensive search of MedLine, Cochrane Library, Embase and the National Guideline Clearinghouse did not yield evidence-based management guidelines for forearm arterial laceration injury. No professional or societal consensus guidelines or best practice guidelines exist to our knowledge. DISCUSSION: The optimal methods for achieving hemostasis are by a combination approach utilizing direct digital pressure, temporary tourniquet pressure, compressive dressings followed by wound closure. While surgical hemostasis may provide an expedited route for control of hemorrhage, this aggressive approach is often not needed (with a few exceptions) to achieve hemostasis for most forearm lacerations. Conservative methods mentioned above will attain the same result. Further, routine emergent or urgent operative exploration of forearm laceration injuries are not warranted and not cost-beneficial. It has been widely accepted with ample evidence in the literature that neither injury to forearm artery, nerve or tendon requires immediate surgical repair. Attention should be directed instead to control of bleeding, and perform a complete physical examination of the hand to document the presence or absence of other associated injuries. Critical ischemia will require expeditious surgical restoration of arterial perfusion. In a well-perfused hand, however, the presence of one intact artery is adequate to sustain viability without long-term functional disability, provided the palmar arch circulation is intact. Early consultation with a hand specialist should be pursued, and follow-up arrangement made for delayed primary repair in cases of complex injury. CONCLUSION: Management in accordance with well-established clinical principles will maximize treatment efficacy and functional outcome while minimizing the cost of medical care.

Evaluation of a new CPC-to-gauge bonding technique with the use of in vitro fluid flow.

Strain gauging enables the measurement of bone deformation during physical activity, leading to a better understanding of the physiological effects of loading on bone growth and remodeling. Development of a technology that will withstand long-term in vivo exposure and bond securely to bone is imperative for accurate, consistent measurement collection. Polysulfone is currently used to attach calcium-phosphate ceramic (CPC) particles, which promote bone-to-gauge bonding, to polyimide-backed strain gauges. This study evaluated the use of an implant-grade epoxy as an alternative CPC-polyimide adhesive. Polyimide-epoxy-CPC interfaces were loaded to failure and shear strengths calculated. In vitro studies providing a constant flow of medium over test specimens were designed, and long-term in vitro fluid exposure studies of the epoxy's shear strength were conducted. Average shear strength of polysulfone-polyimide interfaces were reported to be 7 MPa. The average shear strength of the epoxy-polyimide interface before long-term in vitro exposure was 17 MPa, which is stronger than the shear strength of the bone-CPC interface. The strength of the epoxy-polyimide interface decreased to 6.8 MPa after 24 weeks in vitro and 3 MPa after 24 weeks in vivo.

Bilateral symmetry of biomechanical properties in mouse femora.

Bone healing and remodeling are commonly examined in animal models by comparing one femur (experimental) to the contralateral femur (control) with the assumption that they are identical with respect to their biomechanical properties. While past studies have characterized the symmetry in geometrical properties in many types of animal bones, few studies have compared the symmetry in the biomechanical properties. The purpose of this study was to determine whether there is symmetry in the mechanical properties of mouse femora. Strain gauges were attached to the posterior surface of the femora of C57BL/6 mice, parallel to the long axis of the bone. The femora were mechanically tested in cantilever bending while strain values were recorded. Moments of inertia, cortical areas, and moduli of elasticity were determined from strains and cross-sectional properties. Mouse femora demonstrated an average strain difference of 0.4% in tension and 1.4% in compression. Elastic moduli differed by 6.6% and 0.9% in tension and compression, respectively, and failure strength differed by an average of 2.0%. Statistical analysis showed there were no significant differences in strain, modulus, or failure load values for the mice, indicating mechanical and geometrical symmetry of mouse femora in cantilever bending.

Axonal loss in murine peripheral nerves following exposure to recombinant human bone morphogenetic protein-2 in an absorbable collagen sponge.

BACKGROUND: With the proven efficacy of recombinant human bone morphogenetic protein-2 (rhBMP-2) to treat open tibial fractures and promote spine fusion, there has been an increase in its off-label use. Recent studies have shown that BMPs play a role in nerve development and regeneration. Little is known about changes that result when rhBMP-2 is used in the vicinity of peripheral nerves. The purpose of this study is to characterize changes in peripheral nerves following exposure to rhBMP-2-soaked collagen sponges. METHODS: rhBMP-2 on an absorbable collagen sponge (ACS) was implanted directly on the sciatic nerves of Wistar rats. One and three weeks following surgery, the nerves were harvested and histological analysis was performed to evaluate inflammatory and structural changes. RESULTS: rhBMP-2-soaked collagen sponges induced ectopic bone formation in muscle tissue in all animals after three weeks, but did not cause bone formation within the nerve. Axonal swelling and splitting of the myelin sheath were observed in both experimental and control nerves and may be a result of surgical manipulation. The overall incidence of axonal loss was 15.8% in the rhBMP-2/ACS-exposed nerves and was 0% in control nerves (p < 0.05). CONCLUSIONS: rhBMP-2-soaked collagen sponges may adversely affect the axons of peripheral nerves by causing axonal dropout and loss of axons. Ectopic bone formation occurs within muscle tissues and not within the peripheral nerve. The axonal dropout may be a direct effect of rhBMP-2-soaked collagen sponges and not nerve compression as it was observed prior to ectopic bone formation.

Biomechanical evaluation of suture-augmented locking plate fixation for proximal third fractures of the olecranon.

OBJECTIVES: To describe a method of suture augmentation of locking plate fixation (PF) of proximal olecranon fractures and to evaluate the biomechanical effectiveness of the suture augmentation using a human cadaveric model. METHODS: Six matched pairs of cadaveric elbows were used. Proximal one-third fractures of the olecranon were simulated via a transverse osteotomy. Identical locking PF was performed on each elbow using olecranon locking plates. One elbow of each pair was assigned to suture augmentation of the construct. The choice of left/right specimen for augmentation was performed in an alternating fashion. Augmentation was performed using a no. 2 ultra-high-molecular weight polyethylene-braided suture attaching the triceps to the plate via a modified Krackow stitch. The elbows were mounted into a custom jig and linearly loaded to failure using a hydraulic testing machine. Load to and modes of failure were recorded for each sample. The data were analyzed using the Wilcoxon signed-rank test for nonparametric distributions. RESULTS: Suture augmentation improved the single load-to-failure strength in all pairs. One pair was excluded due to failure of the triceps attachment to the test machine. A median 398 N (P = 0.04 range, 197-633 N) or a median 48% (range, 30%-130%) improvement in strength was seen. The most common mode of failure was loss of fixation of the proximal olecranon fragment. CONCLUSIONS: Suture augmentation can significantly increase the single load-to-failure strength of locking PF for proximal olecranon fractures.

Evaluation of the osteogenic performance of calcium phosphate-chitosan bone fillers.

There has been recent interest in utilizing calcium phosphates (CaPs) that set in situ for treating bone defects due to the limitations associated with morselized autografts and allografts. However, CaP cements have long setting times, poor mechanical properties, and poor osteoinductivity. This has prompted research toward finding a nonprotein-based compound, such as chitosan, to accelerate setting times and increase osteoinductivity. The purpose of this study was to compare bone growth rates during the early bone healing response achieved using conventionally prepared chitosan-CaP bone filler to an extensively purified chitosan-CaP compound. Both compounds set quickly and stimulated bone formation. Histomorphometry demonstrated a 290% increase in new bone formation when using the conventional chitosan-CaP bone filler and a 172% increase with the highly purified chitosan-CaP compound compared to the increase in bone formation seen with the unfilled control group. The results of this study indicate that a highly purified chitosan-CaP paste stimulated less bone formation than a conventionally prepared chitosan-CaP paste but both pastes have the potential to stimulate bone formation.

Load measurement accuracy from sensate scaffolds with and without a cartilage surface.

ABSTRACT The use of "sensate" scaffolds covered with tissue-engineered cartilage has emerged as a possible treatment option for focal articular cartilage defects. The ability to monitor joint loading provides several benefits that can be useful in both clinical and research situations. Previous studies have shown that these scaffolds can accurately monitor in vivo joint loading during various activities. However, the effect that an articular cartilage layer or soft tissue overgrowth has on scaffold sensitivity has not been tested. Eight scaffolds were tested with cartilage samples taken from four hounds. Three strain gauges were attached to each scaffold and a servo hydraulics system was used to test sensitivity while the scaffold was in contact with cartilage, metal, or silicone surfaces. Strain gauge sensitivity was calculated from load and strain measurements collected during testing. There was no significant difference between the mean strain gauge sensitivities when the scaffolds were in contact with the different surfaces: cartilage 30.9 +/- 16.2 muepsilon/N, metal 31.8 +/- 18.6 muepsilon/N, and silicone 30.6 +/- 12.3 muepsilon/N. These results indicate that "sensate" scaffolds can be calibrated and used to monitor load with the presence of an articular cartilage layer.

A novel biomimetic polymer scaffold design enhances bone ingrowth.

There has been recent interest in treating large bone defects with polymer scaffolds because current modalities such as autographs and allographs have limitations. Additionally, polymer scaffolds are utilized in tissue engineering applications to implant and anchor tissues in place, promoting integration with surrounding native tissue. In both applications, rapid and increased bone growth is crucial to the success of the implant. Recent studies have shown that mimicking native bone tissue morphology leads to increased osteoblastic phenotype and more rapid mineralization. The purpose of this study was to compare bone ingrowth into polymer scaffolds created with a biomimetic porous architecture to those with a simple porous design. The biomimetic architecture was designed from the inverse structure of native trabecular bone and manufactured using solid free form fabrication. Histology and muCT analysis demonstrated a 500-600% increase in bone growth into and adjacent to the biomimetic scaffold at five months post-op. This is in agreement with previous studies in which biomimetic approaches accelerated bone formation. It also supports the applicability of polymer scaffolds for the treatment of large tissue defects when implanting tissue-engineering constructs. (c) 2008 Wiley Periodicals, Inc. J Biomed Mater Res, 2009.

Phenotypic characteristics of bone in carbonic anhydrase II-deficient mice.

Carbonic anhydrase II (CAII)-deficient mice were created to study the syndrome of CAII deficiency in humans including osteopetrosis, renal tubular acidosis, and cerebral calcification. Although CAII mice have renal tubular acidosis, studies that analyzed only cortical bones found no changes characteristic of osteopetrosis. Consistent with previous studies, the tibiae of CAII-deficient mice were significantly smaller than those of wild-type (WT) mice (28.7 +/- 0.9 vs. 43.6 +/- 3.7 mg; p < 0.005), and the normalized cortical bone volume of CAII-deficient mice (79.3 +/- 2.2%) was within 5% of that of WT mice (82.7 +/- 2.3%; p < 0.05), however, metaphyseal widening of the tibial plateau was noted in CAII-deficient mice, consistent with osteopetrosis. In contrast to cortical bone, trabecular bone volume demonstrated a nearly 50% increase in CAII-deficient mice (22.9 +/- 3.5% in CAII, compared to 15.3 +/- 1.6% in WT; p < 0.001). In addition, histomorphometry demonstrated that bone formation rate was decreased by 68% in cortical bone (4.77 +/- 1.65 microm3/microm2/day in WT vs. 2.07 +/- 1.71 microm3/microm2/day in CAII mice; p < 0.05) and 55% in trabecular bone (0.617 +/- 0.230 microm3/microm2/day in WT vs. 0.272 +/- 0.114 microm3/microm2/day in CAII mice; p < 0.05) in CAII-deficient mice. The number of osteoclasts was significantly increased (67%) in CAII-deficient mice, while osteoblast number was not different from that in WT mice. The metaphyseal widening and changes in the trabecular bone are consistent with osteopetrosis, making the CAII-deficient mouse a valuable model of human disease.