Intra-Operative Bioprinting of Hard, Soft, and Hard/Soft Composite Tissues for Craniomaxillofacial Reconstruction.

Reconstruction of complex craniomaxillofacial (CMF) defects is challenging due to the highly organized layering of multiple tissue types. Such compartmentalization necessitates the precise and effective use of cells and other biologics to recapitulate the native tissue anatomy. In this study, intra-operative bioprinting (IOB) of different CMF tissues, including bone, skin, and composite (hard/soft) tissues, is demonstrated directly on rats in a surgical setting. A novel extrudable osteogenic hard tissue ink is introduced, which induced substantial bone regeneration, with ≈80% bone coverage area of calvarial defects in 6 weeks. Using droplet-based bioprinting, the soft tissue ink accelerated the reconstruction of full-thickness skin defects and facilitated up to 60% wound closure in 6 days. Most importantly, the use of a hybrid IOB approach is unveiled to reconstitute hard/soft composite tissues in a stratified arrangement with controlled spatial bioink deposition conforming the shape of a new composite defect model, which resulted in ≈80% skin wound closure in 10 days and 50% bone coverage area at Week 6. The presented approach will be absolutely unique in the clinical realm of CMF defects and will have a significant impact on translating bioprinting technologies into the clinic in the future.

Finite Element Analysis of Fracture Fixation.

PURPOSE OF REVIEW: Fracture fixation aims to provide stability and promote healing, but remains challenging in unstable and osteoporotic fractures with increased risk of construct failure and nonunion. The first part of this article reviews the clinical motivation behind finite element analysis of fracture fixation, its strengths and weaknesses, how models are developed and validated, and how outputs are typically interpreted. The second part reviews recent modeling studies of the femur and proximal humerus, areas with particular relevance to fragility fractures. RECENT FINDINGS: There is some consensus in the literature around how certain modeling aspects are pragmatically formulated, including bone and implant geometries, meshing, material properties, interactions, and loads and boundary conditions. Studies most often focus on predicted implant stress, bone strain surrounding screws, or interfragmentary displacements. However, most models are not rigorously validated. With refined modeling methods, improved validation efforts, and large-scale systematic analyses, finite element analysis is poised to advance the understanding of fracture fixation failure, enable optimization of implant designs, and improve surgical guidance.

Increased Load to Failure in Biceps Tenodesis With All-Suture Suture Anchor Compared With Interference Screw: A Cadaveric Biomechanical Study.

PURPOSE: To compare the biomechanical characteristics of a single radially expanding all-suture anchor with an interference screw for open subpectoral long head of biceps tendon (LHBT) tenodesis. METHODS: Eighteen fresh-frozen matched-pair human cadaveric humeri were used for this biomechanical study. The matched pair humeri were randomly assigned into 2 experimental biceps tenodesis groups: conventional interference screw (CIS) or all-suture suture anchor (ASSA). Open subpectoral LHBT tenodesis was then performed and biomechanical testing was performed using a servohydraulic test frame. A preload of 5 N was applied for 2 minutes before cyclic loading. Displacement was recorded at cycle 300 (D300) and cycle 500 (D500) and at ultimate failure. Data recorded included displacement, load to failure, displacement at failure. Paired t test was used for analysis. RESULTS: Decreased displacement was observed for the CIS group at D300 (1.67 ± 0.57 mm vs 3.35 ± 2.24 mm; P = .04), D500 (2.00 ± 0.76 mm vs 3.87 ± 2.20 mm; P = .04), and at failure (5.17 ± 3.05 mm vs 10.76 ± 2.66 mm; P < .001). Load to failure was lower in CIS specimens (170 ± 24.5 N vs 217.8 ± 51.54 N; P = .02). Failure in each case was tendon pullout for all CIS specimens; in ASSA 6 specimens failed as the suture pulled through the tendon, 2 specimens failed by suture breakage. No difference in stiffness was observed between the 2 groups (CIS = 98.33 ± 22.98 N/m vs ASSA = 75.94 ± 44.83 N/m; P = .20). CONCLUSIONS: Our study found that open subpectoral biceps tenodesis performed with an ASSA construct results in increased load to failure as compared with CIS. However, the CIS did demonstrate decreased displacement as compared to ASSA in this cadaveric biomechanical study. CLINICAL RELEVANCE: ASSA and CIS at time zero provide fixation as indicated by the provider intraoperatively for LHBT tenodesis. ASSA, however, does remove less cortical bone than does CIS and therefore produces a smaller stress riser in the proximal humerus. Further testing as to the integrity of ASSA is warranted to determine the integrity of the tenodesis with cyclical loading.

Nicotine Exposure Via Electronic Cigarettes Significantly Impedes Biomechanical Healing Properties of Tendon Healing in a Rat Model.

PURPOSE: To evaluate the biomechanical and histologic effects on Achilles tendon repair of inhaled combusted tobacco versus nicotine exposure via electronic cigarette versus a control group in a small-animal model (Sprague-Dawley rat). METHODS: Fifty-four Sprague-Dawley rats were randomized into 3 groups: combusted tobacco, e-cigarettes, or control. Experimental rats were exposed to research cigarettes or e-cigarette vapor in a smoking chamber for 4 weeks. Surgical transection and repair of the Achilles tendon were then completed, followed by 2 additional weeks of exposure. Achilles tendons were harvested, and biomechanical tensile testing was performed. Histologic evaluation was completed, including hematoxylin-eosin staining, trichrome staining, and immunohistochemistry analysis for type I and type III collagen. RESULTS: The control group showed the highest mean tensile load to failure, at 41.0 ± 10.4 N (range, 18.3-55.1 N); the cigarette cohort had the second highest mean, at 37.3 ± 11.1 N (range, 14.0-54.7 N); and finally, the vaping group had the lowest mean, at 32.3 ± 8.4 N (range, 17.8-45.1 N). One-way analysis of variance showed a significant difference in load to failure when comparing the control group with the e-cigarette group (P = .026). No statistical difference was detected between the control group and cigarette group (P = .35) or between the e-cigarette group and cigarette group (P = .23). Stiffness and qualitative histologic analysis showed no difference among groups. CONCLUSIONS: This investigation shows that in a rat model, nicotine exposure via e-cigarette significantly impedes the biomechanical healing properties of Achilles tendon surgical repair. CLINICAL RELEVANCE: The results indicate that although e-cigarettes are often used as a perceived "safer" alternative to smoking, their use may have a detrimental effect on tendon load to failure.

Finite Element-Predicted Effects of Screw Configuration in Proximal Humerus Fracture Fixation.

Internal fixation with the use of locking plates is the standard surgical treatment for proximal humerus fractures, one of the most common fractures in the elderly. Screw cut-out through weak cancellous bone of the humeral head, which ultimately results in collapse of the fixed fracture, is the leading cause of failure and revision surgery. In an attempt to address this problem, surgeons often attach the plate with as many locking screws as possible into the proximal fragment. It is not thoroughly understood which screws and screw combinations play the most critical roles in fixation stability. This study conducted a detailed finite element analysis to evaluate critical parameters associated with screw cut-out failure. Several clinically relevant screw configurations and fracture gap sizes were modeled. Findings demonstrate that in perfectly reduced fracture cases, variation of the screw configurations had minor influence on mechanical stability of the fixation. The effects of screw configurations became substantial with the existence of a fracture gap. Interestingly, the use of a single anterior calcar screw was as effective as utilizing two screws to support the calcar. On the other hand, the variation in calcar screw configuration had minor influence on the fixation stability when all the proximal screws (A-D level) were filled. This study evaluates different screw configurations to further understand the influence of combined screw configurations and the individual screws on the fixation stability. Findings from this study may help decrease the risk for screw cut-out with proximal humerus varus collapse and the associated economic costs.

Blockade of the OGF-OGFr pathway in diabetic bone.

Purpose: This research investigated the presence and integrity of the opioid growth factor (OGF)-opioid growth factor receptor (OGFr) regulatory pathway in type 1 diabetic (T1D) rats, and investigated whether modulation of this axis by naltrexone (NTX) altered the composition of normal bone or fractured femurs. Materials and Methods: Diabetes was induced by streptozotocin; controls rats received buffer. Hyperglycemic animals were subjected to femur osteotomy, with randomized cohorts receiving either topical NTX or sterile saline in calcium carbonate. In experiment 2, hyperglycemic rats were injected daily for 3 weeks with either 30 mg/kg NTX or sterile saline. Expression levels of OGF and OGFr were measured by immunohistochemistry, bone composition was assessed by histomorphometry, and bone integrity was evaluated by µCT and 3-point bending. Results: Relative to normoglycemic bones, OGF and OGFr expression levels were increased 95% and 84%, respectively, in T1D bone; serum levels of OGF in T1D rats were elevated 23%. Hyperglycemia decreased the strength (26%), osteocalcin expression (17%), and number of proliferative (Ki67+) cells (32%) in intact femur. Topical NTX treatment of fractured femurs reduced the percentage of granulation tissue and increased cartilage. Systemic NTX treatment of diabetic rats increased strength by 21% and energy absorbed by105% in bone relative to measurements in saline-treated diabetic rats. Conclusions: The OGF-OGFr pathway appears to be dysregulated in the bone of T1D rats. Topical NTX treatment of T1D fractured bone accelerated some aspects of delayed diabetic fracture repair, and systemic NTX protected against some elements of compromised bone composition.

Effect of Transosseous Tunnels on Patella Fracture Risk After Medial Patellofemoral Ligament Reconstruction: A Cadaveric Study.

PURPOSE: To determine whether (1) tunnels that breach the anterior cortex of the patella result in increased fracture risk and (2) transosseous tunnels drilled across the patella significantly reduce the tensile force needed to fracture the patella. METHODS: Twenty-six fresh-frozen cadaveric human patellas were randomized to 1 of 3 groups: a control group with unmodified patellas, a group with 2 transverse tunnels (TT) that did not breach the anterior cortex, and a group with 2 TT that breached the anterior cortex of the patella (PA). Patellas were connected in series to a load cell via freeze clamp attachments to the quadriceps and patellar tendons. Pull was fixed at 45° with the patella set in the trochlear groove of a synthetic femur. Patellas were loaded cyclically, then to failure. RESULTS: Twenty-six patellas were tested (mean age = 71.4 years; range = 37-95, standard deviation [STD] = 11.5 years). PA patellas were more likely to fracture through the tunnel than TT patellas (100% vs 25%, P = .033). Control, TT, and PA groups failed at 1,915 N (STD = 508 N), 1,901 N (STD = 884 N), and 1,640 N (STD = 625 N), respectively. There was no statistically significant difference in overall load to failure between control and TT (P = .969), control and PA (P = .321), and TT and PA (P = .488) groups. CONCLUSIONS: Transosseous patellar tunnels for medial patellofemoral ligament reconstruction that breached the anterior cortex were more likely to fracture during longitudinal load than those that did not breach the anterior cortex. However, we found no statistically significant difference in the tensile load to failure between native patellas and patellas with either type of transosseous tunnel. CLINICAL RELEVANCE: The results of this study show that breaching the anterior cortex during transosseous drilling increases the risk of a patellar fracture occurring through the transosseous tunnel.

Interdepartmental imaging protocol for clinically based three-dimensional computed tomography can provide accurate measurement of glenoid version.

BACKGROUND: Conventional computed tomography (CT) is not accurate for glenoid version measurement. This study sought to examine the feasibility of an interdepartmental protocol implemented between orthopedic surgery and radiology departments for acquisition of anatomic axial CT images and to validate the glenoid version measured through such a protocol. MATERIALS AND METHODS: Data of 30 conventional CT scans of 10 normal and 20 osteoarthritic glenoids were transferred to clinical 3-dimensional imaging software by a radiology technician trained for the study. The technician independently reoriented the scapulae to generate anatomic CT images. A separate team of orthopedic researchers used laboratory-based 3-dimensional reconstruction software (Mimics; Materialise, Leuven, Belgium) to generate anatomic axial images. Three independent examiners measured glenoid version on the conventional CT, reoriented anatomic CT, and Mimics images at the superior, middle, and inferior levels. Data were analyzed using the Mimics data as the "gold standard." RESULTS: Reoriented anatomic CT images generated by the technician resulted in almost identical version measurements to the Mimics images in both normal and arthritic glenoids. The conventional CT images had poor agreement with the Mimics images in normal glenoids but had good agreement in arthritic glenoids. Both normal and arthritic glenoids had increased retroversion superiorly (P < .05), and this phenomenon was significantly exaggerated on the conventional CT images (P < .05). CONCLUSIONS: This study demonstrated that an interdepartmental protocol can produce reoriented anatomic axial CT images on which true glenoid version can be accurately measured. Such an institutional protocol would help surgeons accurately evaluate glenoid version preoperatively with reduced workload and expense.

Effect of ulnar tunnel location on elbow stability in double-strand lateral collateral ligament reconstruction.

BACKGROUND: Double-strand lateral ulnar collateral ligament (LUCL) reconstruction is an effective treatment for posterolateral rotatory instability (PLRI) of the elbow, but anatomic landmarks for ulnar tunnel placement are often difficult to identify intraoperatively, which potentially can result in a nonanatomic LUCL reconstruction. This study investigated the effect of ulnar tunnel location on joint stability in double-strand LUCL reconstruction. METHODS: PLRI was artificially created in 7 cadaveric elbows, and double-strand LUCL reconstruction was performed. Five different ulnar tunnels were made along the length of the ulna. In each specimen, each possible pair of 2 tunnels (10 total) were used for graft passage. Varus and posterolateral joint gapping was measured after joint loading using a 3-dimensional digitizer system and X-ray image intensifier. RESULTS: No significant gapping was observed at the posterolateral ulnohumeral joint regardless of the location of the ulnar tunnels (P > .05). In contrast, the lateral radiocapitellar joint showed statistically significant varus gapping when both ulnar tunnels were placed proximal to the radial head-neck junction (P < .05). DISCUSSION: This findings of study suggest that the location of the ulnar tunnels may not be as critical as that of the humeral tunnel during double-strand LUCL reconstruction and that posterolateral rotatory elbow stability can be achieved reasonably well as long as at least 1 of the 2 ulnar tunnels is located at or distal to the radial head-neck junction level.

Glenoid cement mantle characterization using micro-computed tomography of three cement application techniques.

BACKGROUND: Numerous studies have documented the concern for progressive radiolucent lines, signifying debonding and subsequent aseptic loosening of the glenoid component. In this study, we compared 3 cementation methods to secure a central peg in 15 cadaveric glenoids. METHODS: Cement application techniques consisted of (1) compression of multiple applications of cement using manual pressure over gauze with an Adson clamp, (2) compression of multiple applications of cement using a pressurizer device, and (3) no compression of a single application of cement. Each glenoid was then imaged with high-resolution micro-computed tomography and further processed by creating 3-dimensional computerized models of implant, bone, and cement geometry. Cement morphology characteristics were then analyzed in each of the models. RESULTS: There were no significant differences detected between the 2 types of compression techniques; however, there was a significant difference between compression methods and use of no compression at all. All morphologic characteristics of a larger cement mantle were significantly correlated with greater cortical contact. CONCLUSIONS: We demonstrate that compression techniques create a larger cement mantle. Increased size of the cement mantle is associated with increased contact with cortical bone at the glenoid vault. This method for characterizing the cement mantle by micro-computed tomography scanning techniques and 3-dimensional analysis may also be useful in future finite element analysis studies.

Effects of Medial Displacement Calcaneal Osteotomy and Calcaneal Z Osteotomy on Subtalar Joint Pressures: A Cadaveric Flatfoot Model.

Medial displacement calcaneal osteotomies have been shown to be successful in the surgical management of adult acquired flatfoot, in particular, stage 2 deformity. Classically, the medial displacement calcaneal osteotomy technique has been performed. However, a calcaneal Z osteotomy has been more recently described and applied in the surgical management of flatfoot deformity. Although the potential advantages of the calcaneal Z technique have been reported, data on its effect on the subtalar joint are lacking. A validated flatfoot model was induced in 8 cadaveric feet that had been randomly assigned to either medial displacement calcaneal osteotomy (n = 4) or calcaneal Z osteotomy (n = 4). The feet were loaded through the tibia with a constant ground reaction force of 400 N, with a simultaneous increase in the Achilles tendon force to 300 or 500 N. The subtalar joint pressures were recorded before and after osteotomy. We did not detect any statistically significant differences between the 2 techniques in terms of their effects on subtalar joint pressure.

Reduced lentivirus susceptibility in sheep with TMEM154 mutations.

Visna/Maedi, or ovine progressive pneumonia (OPP) as it is known in the United States, is an incurable slow-acting disease of sheep caused by persistent lentivirus infection. This disease affects multiple tissues, including those of the respiratory and central nervous systems. Our aim was to identify ovine genetic risk factors for lentivirus infection. Sixty-nine matched pairs of infected cases and uninfected controls were identified among 736 naturally exposed sheep older than five years of age. These pairs were used in a genome-wide association study with 50,614 markers. A single SNP was identified in the ovine transmembrane protein (TMEM154) that exceeded genome-wide significance (unadjusted p-value 3×10(-9)). Sanger sequencing of the ovine TMEM154 coding region identified six missense and two frameshift deletion mutations in the predicted signal peptide and extracellular domain. Two TMEM154 haplotypes encoding glutamate (E) at position 35 were associated with infection while a third haplotype with lysine (K) at position 35 was not. Haplotypes encoding full-length E35 isoforms were analyzed together as genetic risk factors in a multi-breed, matched case-control design, with 61 pairs of 4-year-old ewes. The odds of infection for ewes with one copy of a full-length TMEM154 E35 allele were 28 times greater than the odds for those without (p-value<0.0001, 95% CI 5-1,100). In a combined analysis of nine cohorts with 2,705 sheep from Nebraska, Idaho, and Iowa, the relative risk of infection was 2.85 times greater for sheep with a full-length TMEM154 E35 allele (p-value<0.0001, 95% CI 2.36-3.43). Although rare, some sheep were homozygous for TMEM154 deletion mutations and remained uninfected despite a lifetime of significant exposure. Together, these findings indicate that TMEM154 may play a central role in ovine lentivirus infection and removing sheep with the most susceptible genotypes may help eradicate OPP and protect flocks from reinfection.

Testing of a novel pin array guide for accurate three-dimensional glenoid component positioning.

BACKGROUND: A substantial challenge in total shoulder replacement is accurate positioning and alignment of the glenoid component. This challenge arises from limited intraoperative exposure and complex arthritic-driven deformity. We describe a novel pin array guide and method for patient-specific guiding of the glenoid central drill hole. We also experimentally tested the hypothesis that this method would reduce errors in version and inclination compared with 2 traditional methods. METHODS: Polymer models of glenoids were created from computed tomography scans from 9 arthritic patients. Each 3-dimensional (3D) printed scapula was shrouded to simulate the operative situation. Three different methods for central drill alignment were tested, all with the target orientation of 5° retroversion and 0° inclination: no assistance, assistance by preoperative 3D imaging, and assistance by the pin array guide. Version and inclination errors of the drill line were compared. RESULTS: Version errors using the pin array guide (3° ± 2°) were significantly lower than version errors associated with no assistance (9° ± 7°) and preoperative 3D imaging (8° ± 6°). Inclination errors were also significantly lower using the pin array guide compared with no assistance. DISCUSSION AND CONCLUSION: The new pin array guide substantially reduced errors in orientation of the central drill line. The guide method is patient specific but does not require rapid prototyping and instead uses adjustments to an array of pins based on automated software calculations. This method may ultimately provide a cost-effective solution enabling surgeons to obtain accurate orientation of the glenoid.

Time-resolved Characterization of Particle Associated Polycyclic Aromatic Hydrocarbons using a newly-developed Sequential Spot Sampler with Automated Extraction and Analysis.

A versatile and compact sampling system, the Sequential Spot Sampler (S3) has been developed for pre-concentrated, time-resolved, dry collection of fine and ultrafine particles. Using a temperature-moderated laminar flow water condensation method, ambient particles as small as 6 nm are deposited within a dry, 1-mm diameter spot. Sequential samples are collected on a multiwell plate. Chemical analyses are laboratory-based, but automated. The sample preparation, extraction and chemical analysis steps are all handled through a commercially-available, needle-based autosampler coupled to a liquid chromatography system. This automation is enabled by the small deposition area of the collection. The entire sample is extracted into 50-100µl volume of solvent, providing quantifiable samples with small collected air volumes. A pair of S3 units was deployed in Stockton (CA) from November 2011 to February 2012. PM2.5 samples were collected every 12 hrs, and analyzed for polycyclic aromatic hydrocarbons (PAHs). In parallel, conventional filter samples were collected for 48 hrs and used to assess the new system's performance. An automated sample preparation and extraction was developed for samples collected using the S3. Collocated data from the two sequential spot samplers were highly correlated for all measured compounds, with a regression slope of 1.1 and r2=0.9 for all measured concentrations. S3/filter ratios for the mean concentration of each individual PAH vary between 0.82 and 1.33, with the larger variability observed for the semivolatile components. Ratio for total PAH concentrations was 1.08. Total PAH concentrations showed similar temporal trend as ambient PM2.5 concentrations. Source apportionment analysis estimated a significant contribution of biomass burning to ambient PAH concentrations during winter.

Finite element modeling of fracture compression by compression plates.

Dynamic compression plating is a common type of fracture fixation used to compress between bone fragments. The quality of compression across the fracture is important for postoperative stability and primary bone healing. Compression quality may be affected by surgical variations in plate prebend, screw location, screw torque, fracture gap, and implant material. Computational modeling provides a tool for systematically examining these factors, and for visualizing the mechanisms involved. The purpose of this study was to develop a finite element model of dynamic compression plating that includes screw insertion under torque control, establish model credibility through sensitivity analyses and experimental validation, and use the model to examine the effects of surgical variables on fracture compression and postoperative stability. Model-predicted compressive pressures had good agreement with corresponding synthetic bones experiments under a variety of conditions. Models demonstrated that introducing a 1.5 or 3 mm plate prebend (using a 4.5 mm narrow LCP plate) eliminated gapping at the far cortex, which is consistent with clinical recommendations. However, models also revealed that plate prebend led to sharp decreases in fracture compressive force, exceeding 80% in some cases. A 1.5 mm plate prebend resulted in the most uniform pressures across the fracture. Testing of a simplified model form used in previous computational modeling studies showed large inaccuracies for constructs with plate prebend. This study provides the first experimentally validated computational models of dynamic compression plate fracture fixation, and reveals important effects of plate prebend and fracture gap on fracture compression quality.

Mechanics of dynamic compression plate application in fracture fixation.

BACKGROUND: Dynamic compression plating is a fundamental type of bone fracture fixation used to generate interfragmentary compression. The goal of this study was to investigate the mechanics of the surgical application of these plates, specifically how plate prebend, screw location, fracture gap, and applied torque influence the resulting compressive pressures. METHODS: Synthetic bones with transverse fractures were fixed with locking compression plates. One side of the fracture was fixed with locking screws. On the other side of the fracture, a nonlocking screw was inserted eccentrically to induce interfragmentary compression. A pressure mapping sensor within the fracture gap was used to record the resulting pressure distribution. Plate prebends of 0 mm, 1.5 mm, and 3 mm were tested. Three locations of the eccentric screw, four levels of screw torque, and two initial fracture gap conditions also were tested. FINDINGS: With increasing plate prebend, fracture compression pressures shifted significantly toward the far cortex; however, compression force decreased (P < 0.05). The 1.5 mm prebend plate resulted in the greatest contact area. Increasing screw torque generally resulted in greater fracture compression force. The introduction of a 1 mm fracture gap at the far cortex prior to dynamic compression resulted in little or no fracture compression. INTERPRETATION: The model showed that increasing plate prebend results in an increasing shift of fracture compression pressures toward the far cortex; however, this is accompanied by decreases in compressive force. Initial fracture gaps at the far cortex can result in little or no compression.

Transverse patella fracture fixation: A cadaveric biomechanical comparison of cannulated screws and anterior tension band versus low-profile, multiplanar mesh plating.

INTRODUCTION: Multiplanar mesh plating of patella fractures has become more popular in recent years. It was the goal of this study to compare the biomechanical stability of cannulated screw with anterior tension band to multiplanar mesh plating for fixation of transverse patella fractures in cadaver specimens. MATERIALS AND METHODS: Eight matched pairs of fresh frozen cadaveric knees were obtained and soft tissues dissected leaving the extensor mechanism, joint capsule, and retinaculum intact. Transverse fractures were created at the mid-portion of the patella. For each pair, one specimen was repaired using cannulated screws with anterior tension band, and the second was repaired using multiplanar mesh plating. Each specimen underwent cyclic extension loading with loads increasing by 1.1 kg after every 50 cycles. Interfragmentary displacement was measured at the end of each interval at both 5° and 45° of knee flexion angle, with fixation failure defined by >2 mm displacement. RESULTS: The specimens fixed with multiplanar mesh plating survived more cycles and higher loads than the specimens fixed with cannulated screws with anterior tension band (p = 0.011 comparing survival plots). After 150 cycles of extension loading, 3 of 8 of the specimens fixed with screws/tension band had failed, whereas none of the mesh plated specimens had failed. After 400 cycles, 7 of 8 of the screws/tension band had failed, whereas half of the mesh plated specimens had failed. CONCLUSIONS: While a more technically challenging and expensive technique, mesh plating for patella fractures appears to offer greater durability than traditional cannulated screw with tension banding.

Assessment of Scanning Mobility Particle Sizer (SMPS) for online monitoring of delivered dose in an in vitro aerosol exposure system.

Real-time monitoring of dosimetry is critical to mitigating the constraints of offline measurements. To address this need, the use of the Scanning Mobility Particle Sizer (SMPS) to estimate the dose delivered through the Dosimetric Aerosol in Vitro Inhalation Device (DAVID) was assessed. CuO nanoparticles suspended in ethanol at different concentrations (0.01-10 mg/mL) were aerosolized using a Collison nebulizer and diluted with air at a ratio of either 1:3 (setup 1) or 1:18 (setup 2). From the aerosol volume concentrations measured by the SMPS, density of CuO (6.4 g/cm3), collection time (5-30 min), flow rate (0.5 LPM) and deposition area (0.28 cm2), the mass doses (DoseSMPS) were observed to increase exponentially over time and ranged from 0.02 ± 0.001 to 84.75 ± 3.49 µg/cm2. The doses calculated from the Cu concentrations determined by Inductively Coupled Plasma-Optical Emission Spectrometry (ICP-OES) (DoseICP) also increased exponentially over time (0.01 ± 0.01-97.25 ± 1.30 µg/cm2). Regression analysis between DoseICP and DoseSMPS showed R2 ≥ 0.90 for 0.1-10 mg/mL. As demonstrated, the SMPS can be used to monitor the delivered dose in real-time, and controlled delivery of mass doses with a 226-fold range can be attained in ≤30 min in DAVID by adjusting the nebulizer concentration, dilution air and time.

Cannabidiol and Cannabigerol, Nonpsychotropic Cannabinoids, as Analgesics that Effectively Manage Bone Fracture Pain and Promote Healing in Mice.

Bone fractures are among the most prevalent musculoskeletal injuries, and pain management is an essential part of fracture treatment. Fractures heal through an early inflammatory phase, followed by repair and remodeling. Nonsteroidal anti-inflammatory drugs (NSAIDs) are not recommended for fracture pain control as they potently inhibit the inflammatory phase and, thus, impair the healing. Opioids do not provide a better alternative for several reasons, including abuse potential. Accordingly, there is an unmet clinical need for analgesics that effectively ameliorate postfracture pain without impeding the healing. Here, we investigated the analgesic efficacy of two nonpsychotropic cannabinoids, cannabidiol (CBD) and cannabigerol (CBG), in a mouse model for tibial fracture. Mice with fractured tibiae exhibited increased sensitivity to mechanical, cold, and hot stimuli. Both CBD and CBG normalized pain sensitivity to all tested stimuli, and their analgesic effects were comparable to those of the NSAIDs. Interestingly, CBD and CBG promoted bone healing via multiple mechanisms during the early and late phases. During the early inflammatory phase, both cannabinoids increased the abundance of periosteal bone progenitors in the healing hematoma and promoted the osteogenic commitment of these progenitors. During the later phases of healing, CBD and CBG accelerated the fibrocartilaginous callus mineralization and enhanced the viability and proliferation of bone and bone-marrow cells. These effects culminated in higher bone volume fraction, higher bone mineral density, and improved mechanical quality of the newly formed bone. Together, our data suggest CBD and CBG as therapeutic agents that can replace NSAIDs in managing postfracture pain as both cannabinoids exert potent analgesic effects and, at the same time, promote bone healing. © 2023 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).

Toxicity assessment of CeO2 and CuO nanoparticles at the air-liquid interface using bioinspired condensational particle growth.

CeO2 and CuO nanoparticles (NPs) are used as additives in petrodiesel to enhance engine performance leading to reduced diesel combustion emissions. Despite their benefits, the additive application poses human health concerns by releasing inhalable NPs into the ambient air. In this study, a bioinspired lung cell exposure system, Dosimetric Aerosol in Vitro Inhalation Device (DAVID), was employed for evaluating the toxicity of aerosolized CeO2 and CuO NPs with a short duration of exposure (≤10 min vs. hours in other systems) and without exerting toxicity from non-NP factors. Human epithelial A549 lung cells were cultured and maintained within DAVID at the air-liquid interface (ALI), onto which aerosolized NPs were deposited, and experiments in submerged cells were used for comparison. Exposure of the cells to the CeO2 NPs did not result in detectable IL-8 release, nor did it produce a significant reduction in cell viability based on lactate dehydrogenase (LDH) assay, with a marginal decrease (10%) at the dose of 388 µg/cm2 (273 cm2/cm2). In contrast, exposure to CuO NPs resulted in a concentration dependent reduction in LDH release based on LDH leakage, with 38% reduction in viability at the highest dose of 52 µg/cm2 (28.3 cm2/cm2). Cells exposed to CuO NPs resulted in a dose dependent cellular membrane toxicity and expressed IL-8 secretion at a global dose five times lower than cells exposed under submerged conditions. However, when comparing the ALI results at the local cellular dose of CuO NPs to the submerged results, the IL-8 secretion was similar. In this study, we demonstrated DAVID as a new exposure tool that helps evaluate aerosol toxicity in simulated lung environment. Our results also highlight the necessity in choosing the right assay endpoints for the given exposure scenario, e.g., LDH for ALI and Deep Blue for submerged conditions for cell viability.