Assessing minipig compact jawbone quality at the microscale

Preclinical studies often require animal models for in vivo experiments. Particularly in dental research, pig species are extensively used due to their anatomical similarity to humans. However, there is a considerable knowledge gap on the multiscale morphological and mechanical properties of the miniature pigs’ jawbones, which is crucial for implant studies and a direct comparison to human tissue. In the present work, we demonstrate a multimodal framework to assess the jawbone quantity and quality for a minipig animal model that could be further extended to humans. Three minipig genotypes, commonly used in dental research, were examined: Yucatan, G ̈ottingen, and Sinclair. Three animals per genotype were tested. Cortical bone samples were extracted from the premolar region of the mandible, opposite to the teeth growth. Global morphological, compositional, and mechanical properties were assessed using micro-computed tomography (micro-CT) together with Raman spectroscopy and nano- indentation measurements, averaged over the sample area. Local mineral-mechanical relationships were investigated with the site-matched Raman spectroscopy and micropillar compression tests. For this, a novel femtosecond laser ablation protocol was developed, allowing high-throughput micropillar fabrication and testing without exposure to high vacuum. At the global averaged sample level, bone relative mineralization demonstrated a significant difference between the genotypes, which was not observed from the complementary micro-CT measurements. Moreover, bone hardness measured by nanoindentation showed a positive trend with the relative mineralization. For all genotypes, significant differences between the relative mineralization and elastic properties were more pronounced within the osteonal regions of cortical bone. Site-matched micropillar compression and Raman spectroscopy highlighted the differences between the genotypes’ yield stress and mineral to matrix ratios. The methods used at the global level (averaged over sample area) could be potentially correlated to the medical tools used to assess jawbone toughness and morphology in clinics. On the other hand, the local analysis methods can be applied to quantify compressive bone mechanical properties and their relationship to bone mineralization

Composition and micromechanical properties of the femoral neck compact bone in relation to patient age, sex and hip fracture occurrence

Current clinical methods of bone health assessment depend to a great extent on bone mineral density (BMD) measurements. However, these methods only act as a proxy for bone strength and are often only carried out after the fracture occurs. Besides BMD, composition and tissue-level mechanical properties are expected to affect the whole bone's strength and toughness. While the elastic properties of the bone extracellular matrix (ECM) have been extensively investigated over the past two decades, there is still limited knowledge of the yield properties and their relationship to composition and architecture. In the present study, morphological, compositional and micropillar compression bone data was collected from patients who underwent hip arthroplasty. Femoral neck samples from 42 patients were collected together with anonymous clinical information about age, sex and primary diagnosis (coxarthrosis or hip fracture). The femoral neck cortex from the inferomedial region was analyzed in a site-matched manner using a combination of micromechanical testing (nanoindentation, micropillar compression) together with micro-CT and quantitative polarized Raman spectroscopy for both morphological and compositional characterization. Mechanical properties, as well as the sample-level mineral density, were constant over age. Only compositional properties demonstrate weak dependence on patient age: decreasing mineral to matrix ratio (p = 0.02, R2 = 0.13, 2.6 % per decade) and increasing amide I sub-peak ratio I~1660/I~1683 (p = 0.04, R2 = 0.11, 1.5 % per decade). The patient's sex and diagnosis did not seem to influence investigated bone properties. A clear zonal dependence between interstitial and osteonal cortical zones was observed for compositional and elastic bone properties (p  200). The proposed classification algorithm together with the output database of bone tissue properties can be used for the future comparison of existing methods to evaluate bone quality as well as to form a better understanding of the mechanisms through which bone tissue is affected by aging or disease

Regulator of G-protein signaling 1 critically supports CD8+ TRM cell-mediated intestinal immunity.

Members of the Regulator of G-protein signaling (Rgs) family regulate the extent and timing of G protein signaling by increasing the GTPase activity of Gα protein subunits. The Rgs family member Rgs1 is one of the most up-regulated genes in tissue-resident memory (TRM) T cells when compared to their circulating T cell counterparts. Functionally, Rgs1 preferentially deactivates Gαq, and Gαi protein subunits and can therefore also attenuate chemokine receptor-mediated immune cell trafficking. The impact of Rgs1 expression on tissue-resident T cell generation, their maintenance, and the immunosurveillance of barrier tissues, however, is only incompletely understood. Here we report that Rgs1 expression is readily induced in naïve OT-I T cells in vivo following intestinal infection with Listeria monocytogenes-OVA. In bone marrow chimeras, Rgs1 -/- and Rgs1 +/+ T cells were generally present in comparable frequencies in distinct T cell subsets of the intestinal mucosa, mesenteric lymph nodes, and spleen. After intestinal infection with Listeria monocytogenes-OVA, however, OT-I Rgs1 +/+ T cells outnumbered the co-transferred OT-I Rgs1- /- T cells in the small intestinal mucosa already early after infection. The underrepresentation of the OT-I Rgs1 -/- T cells persisted to become even more pronounced during the memory phase (d30 post-infection). Remarkably, upon intestinal reinfection, mice with intestinal OT-I Rgs1 +/+ TRM cells were able to prevent the systemic dissemination of the pathogen more efficiently than those with OT-I Rgs1 -/- TRM cells. While the underlying mechanisms are not fully elucidated yet, these data thus identify Rgs1 as a critical regulator for the generation and maintenance of tissue-resident CD8+ T cells as a prerequisite for efficient local immunosurveillance in barrier tissues in case of reinfections with potential pathogens

Optics and Quantum Electronics

Contains table of contents for Section 2 and reports on eighteen research projects.National Science Foundation (Grant EET 87-00474)Joint Services Electronics Program (Contract DAAL03-86-K-0002)Joint Services Electronics Program (Contract DAALO3-89-C-0001)Charles Stark Draper Laboratory (Grant DL-H-285408)Charles Stark Draper Laboratory (Grant DL-H-2854018)National Science Foundation (Grant EET 87-03404)National Science Foundation (Grant ECS 84-06290)U.S. Air Force - Office of Scientific Research (Contract F49620-88-C-0089)AT&T Bell FoundationNational Science Foundation (Grant ECS 85-52701)National Institutes of Health (Grant 5-RO1-GM35459)Massachusetts General Hospital (Office of Naval Research Contract N00014-86-K-0117)Lawrence Livermore National Laboratory (Subcontract B048704

Optics and Quantum Electronics

Contains reports on eleven research projects.National Science Foundation (Grant EET 87-00474)Joint Services Electronics Program (Contract DAALO03-86-K-O002)Charles Stark Draper Laboratory, Inc. (Grant DL-H-2854018)National Science Foundation (Grant DMR 84-18718)National Science Foundation (Grant EET 87-03404)National Science Foundation (ECS 85-52701)US Air Force - Office of Scientific Research (Contract AFOSR-85-0213)National Institutes of Health (Contract 5-RO1-GM35459)US Navy - Office of Naval Research (Contract N00014-86-K-0117

A biomechanical study comparing the mean load to failure of two different osteosynthesis techniques for step-cut olecranon osteotomy

Background Olecranon osteotomies are frequently used to expose distal humeral intraarticular fractures. The step-cut olecranon osteotomy (SCOOT) is an augmented version of the oblique olecranon osteotomy, which has recently been evaluated biomechanically with tension band wiring (TBW) fixation. However, complications with TBW are common. In this study, we, therefore, compared the mean load to failure of TBW with compression screws for SCOOT fixation. We hypothesized a higher load to failure for the compression screw group. Methods We performed a SCOOT on 36 Sawbones. Eighteen were fixed with TBW, and another 18 with two compression screws. The humeroulnar joint was simulated using an established test setup, which allows the application of triceps traction force through a tendon model to the ulna, while the humeroulnar joint is in a fixed position. Eight models of each fixation group were tested at 20°, and eight at 70° of flexion by isometrical loading until failure, which was defined as either a complete fracture or gap formation of more than 2 mm at the osteotomy site. Results At 20° of flexion, mean load to failure was similar between the TBW group (1360 ± 238 N) and the compression screw group (1401 ± 261 N) (P = .88). Also, at 70° of flexion, the mean load to failure was similar between the TBW group (1398 ± 215 N) and the compression screw group (1614 ± 427 N) (P = .28). Conclusions SCOOTs fixed with TBW and compression screws showed similar loads to failure. A SCOOT fixed with compression screws might be a valuable alternative for surgeons when treating intraarticular distal humeral fractures. However, future in vivo studies are necessary to confirm our results in a clinical setting

Extra-articular step osteotomy of the olecranon: A biomechanical assessment

BACKGROUND Trans-olecranon chevron osteotomies (COs) remain the gold standard surgical approach to type C fractures of the distal humerus. This technique is associated with a high complication rate and development of an extra-articular olecranon osteotomy may be advantageous. The aim of this study was to compare the load to failure of COs with extra-articular oblique osteotomies (OOs) as well as modified, extra-articular step osteotomies (SOs). METHODS These three osteotomies and their subsequent fixation utilizing a standardized tension band wiring technique were tested in 42 composite analog ulnae models at 20° and 70° of flexion. Triceps loading was simulated with a servo hydraulic testing machine. All specimens were isometrically loaded until failure. Kinematic and force data, as well as interfragmentary motion were recorded. RESULTS At 70°, CO failed at a mean load of 963N (SD 104N), the OO at 1512N (SD 208N) and the SO at 1484N (SD 153N), (P<0.001). At 20°, CO failed at a mean load of 707N (SD 104N) and OO at 1009N (SD 85N) (P=0.006). The highest load to failure was observed for the SO, which was 1277N (SD 172N). The load to failure of the SO was significantly higher than the CO as well as the OO. CONCLUSION Extra-articular osteotomies showed a significantly higher load to failure in comparison to traditional CO. At near full extension (20° of flexion), this biomechanical advantage was further enhanced by a step-cut modification of the extra-articular oblique osteotomy