Scleredema Diabeticorum: A Rare Metabolic Connective Tissue Manifestation of Type 2 Diabetes Mellitus Causing External Restrictive Lung Disease.

Scleredema diabeticorum (SD) is a rare metabolic connective tissue manifestation of diabetes mellitus (DM). SD commonly manifests in male patients with poorly controlled prolonged DM with obesity. In SD, the skin gets stiffened, thickened, and leathery in texture with a peau d'orange appearance commonly involving the posterior aspect of the neck and chest wall. Extensive chest wall skin involvement restricts lung movement, causing external restrictive lung disease and hypoventilation. In this case report, we present a 50-year-old male patient with poorly controlled type 2 DM for 10 years, complicated with established diabetic microvascular complications and extensive involvement of SD over the back of the neck and chest with external restrictive lung disease.

Identifying the Morphological and Molecular Features of a Cell-Based Orthotopic Pancreatic Cancer Mouse Model during Growth over Time.

Pancreatic ductal adenocarcinoma (PDAC), characterized by hypovascularity, hypoxia, and desmoplastic stroma is one of the deadliest malignancies in humans, with a 5-year survival rate of only 7%. The anatomical location of the pancreas and lack of symptoms in patients with early onset of disease accounts for late diagnosis. Consequently, 85% of patients present with non-resectable, locally advanced, or advanced metastatic disease at diagnosis and rely on alternative therapies such as chemotherapy, immunotherapy, and others. The response to these therapies highly depends on the stage of disease at the start of therapy. It is, therefore, vital to consider the stages of PDAC models in preclinical studies when testing new therapeutics and treatment modalities. We report a standardized induction of cell-based orthotopic pancreatic cancer models in mice and the identification of vital features of their progression by ultrasound imaging and histological analysis of the level of pancreatic stellate cells, mature fibroblasts, and collagen. The results highlight that early-stage primary tumors are secluded in the pancreas and advance towards infiltrating the omentum at week 5-7 post implantation of the BxPC-3 and Panc-1 models investigated. Late stages show extensive growth, the infiltration of the omentum and/or stomach wall, metastases, augmented fibroblasts, and collagen levels. The findings can serve as suggestions for defining growth parameter-based stages of orthotopic pancreatic cancer models for the preclinical testing of drug efficacy in the future.

Morphological adaptation of the tongue of okapi (Okapia johnstoni Artiodactyla, Giraffidae)-Anatomy, histology, and ultrastructure.

The aim of this study was to describe the morphology of the tongue of the okapi, and to compare the results with other ruminants including browsers, intermediates and grazers. The material was collected post-mortem from two animals from a Zoological Garden. The structure of the okapi tongue, focusing of the shape of the tongue, lingual surface, its papillae and lingual glands, was examined using gross morphology, light and polarized microscopy, and by scanning electron microscopy. The okapi tongue was characterized by dark pigmentation on the lingual dorsum (except lingual torus) and on the whole ventral surface. Two types of filiform papillae were observed, with additional, even 6-8 projections at their base. The round fungiform papillae were present at a higher density, up to 16/cm2, on the ventro-lateral area of the lingual apex. Round and elongate vallate papillae were arranged in two parallel lines between the body and root of the tongue. Numerous taste buds were detected within the epithelium of their vallum, while fungiform papillae had sparse taste buds. A lack of foliate papillae was noted. Very small conical papillae, some lenticular in shape, were present on the lingual torus. Thick collagen type I fibers were dominant over collagen type III fibers in the connective tissue of the lingual papillae. The mucous acini units were dominant among lingual glands, indicating that the secretion of okapi lingual glands was mostly mucous. In many aspects, the tongue of okapi resembles the tongue of other ruminants. The specific lingual shape and lingual surface, together with the lingual glands, support the processing of plant food, such as young and soft leaves. Although okapi tongue is characterized by smaller conical papillae compared to other ruminants, its high number of vallate papillae is similar that found in other browsers, intermediate and grazers. Thus the number of gustatory papillae rather indicates that this feature is not related to the type of feeding.

Full life cycle green preparation of collagen-based food packaging films using Halocynthia roretzi as raw material.

The extraction of collagen for packaging films typically requires a time-consuming process and the use of substantial chemicals. Herein, we present a full life cycle green preparation method for rapidly producing collagen-based food packaging films using Halocynthia roretzi (HR), a collagen-rich marine organism, as raw material. We first prepared the micro/nano-sized collagen fibers from HR tissue by utilizing urea and sonication as effective hydrogen-bond breakers. Subsequently, the collagen fiber was rapidly fabricated into a film through vacuum filtration. The resulting collagen fiber film (CFF) exhibited a uniform and dense surface, along with good tensile properties, water resistance, and biodegradability. In addition, the deposition of chitosan (CS) on the surface of CFF resulted in a remarkable preservation effect for both strawberries and pork. This full life cycle preparation method for collagen-based films provides a promising and innovative approach to the sustainable preparation of food packaging films.

Biomechanical functions analysis of the Mallard webbed foot: A study of macroscopic and microscopic material assembly and tendon morphology.

The mallard webbed foot represents an exemplary model of biomechanical efficiency in avian locomotion. This study delves into the intricate material assembly and tendon morphology of the mallard webbed foot, employing both macroscopic and microscopic analyses. Through histological slices and scanning electron microscopy (SEM), we scrutinized the coupling assembly of rigid and flexible materials such as skin, tendon, and bone, while elucidating the biomechanical functions of tendons across various segments of the tarsometatarsophalangeal joint (TMTPJ). The histological examination unveiled a complex structural hierarchy extending from the external integument to the skeletal framework. Notably, the bone architecture, characterized by compact bone and honeycombed trabeculae, showcases a harmonious blend of strength and lightweight design. Tendons, traversing the phalangeal periphery, surrounded by elastic fibers, collagen fibers, and fat tissue. Fat chambers beneath the phalanx, filled with adipocytes, provide effective buffering, enabling the phalanx to withstand gravity, provide support, and facilitate locomotion. Furthermore, SEM analysis provided insights into the intricate morphology and arrangement of collagen fiber bundles within tendons. Flexor tendons in proximal and middle TMTPJ segments adopt a wavy-type, facilitating energy storage and release during weight-bearing activities. In contrast, distal TMTPJ flexor tendons assume a linear-type, emphasizing force transmission across phalangeal interfaces. Similarly, extensor tendons demonstrate segment-specific arrangements tailored to their respective biomechanical roles, with wavy-type in proximal and distal segments for energy modulation and linear-type in middle segments for enhanced force transmission and tear resistance. Overall, our findings offer a comprehensive understanding of the mallard webbed foot's biomechanical prowess, underscoring the symbiotic relationship between material composition, tendon morphology, and locomotor functionality. This study not only enriches our knowledge of avian biomechanics but also provides valuable insights for biomimetic design and tissue engineering endeavors.

Effects of mechanical ventilation on the interstitial extracellular matrix in healthy lungs and lungs affected by acute respiratory distress syndrome: a narrative review.

BACKGROUND: Mechanical ventilation, a lifesaving intervention in critical care, can lead to damage in the extracellular matrix (ECM), triggering inflammation and ventilator-induced lung injury (VILI), particularly in conditions such as acute respiratory distress syndrome (ARDS). This review discusses the detailed structure of the ECM in healthy and ARDS-affected lungs under mechanical ventilation, aiming to bridge the gap between experimental insights and clinical practice by offering a thorough understanding of lung ECM organization and the dynamics of its alteration during mechanical ventilation. MAIN TEXT: Focusing on the clinical implications, we explore the potential of precise interventions targeting the ECM and cellular signaling pathways to mitigate lung damage, reduce inflammation, and ultimately improve outcomes for critically ill patients. By analyzing a range of experimental studies and clinical papers, particular attention is paid to the roles of matrix metalloproteinases (MMPs), integrins, and other molecules in ECM damage and VILI. This synthesis not only sheds light on the structural changes induced by mechanical stress but also underscores the importance of cellular responses such as inflammation, fibrosis, and excessive activation of MMPs. CONCLUSIONS: This review emphasizes the significance of mechanical cues transduced by integrins and their impact on cellular behavior during ventilation, offering insights into the complex interactions between mechanical ventilation, ECM damage, and cellular signaling. By understanding these mechanisms, healthcare professionals in critical care can anticipate the consequences of mechanical ventilation and use targeted strategies to prevent or minimize ECM damage, ultimately leading to better patient management and outcomes in critical care settings.

Harnessing oriented arrangement of collagen fibers by 3D printing for enhancing mechanical and osteogenic properties of mineralized collagen scaffolds.

As the structural basis of connective and load-bearing tissues, collagen fibers with orientation play an important role in the mechanical properties and physiological and biochemical functions of the tissues, but viable methods for preparing scaffolds with highly oriented collagenous structure still need to be further studied. In this study, pure collagen was used as printing ink to 3D printing. Harnessing oriented collagen fiber structure by 3D printing for promoting mechanical and osteogenic properties of scaffolds. The scaffolds with different printed angles and thicknesses were prepared to fit the bone defect site and realize personalized customization. The orientation assembly of collagen fibers was promoted by shear force action of 3D printing, the regular arrangement of collagen fibers and stabilization of fiber structure were promoted by pH adjustment and glutaraldehyde cross-linking, and the collagen fibers were mineralized by cyclic mineralization method. The microscopic morphology of fiber arrangement in the scaffolds were investigated by scanning electron microscopy. Results demonstrated that collagen fibers were changed from non-oriented to oriented after 3D printing. And the tensile modulus of the scaffolds with oriented collagen fibers was nine times higher than that of the scaffolds with non-oriented fibers. Moreover, the effects of oriented collagen fibers on the proliferation, differentiation and mineralization of MC3T3-E1 cells were studied by CCK-8 assay, live/dead cell staining, alkaline phosphatase activity test, and Alizarin red staining. The results indicated that cell proliferation, differentiation and mineralization were significantly promoted by oriented collagen fibers, and the cells proliferated directionally in the direction of the fibers. Taken together, mineralized collagen fiber scaffolds with oriented collagen fibers have great potential in bone tissue engineering applications.

Improving hemocompatibility of decellularized vascular tissue by structural modification of collagen fiber.

Decellularized vascular tissue has high potential as a tissue-engineered vascular graft because of its similarity to native vessels in terms of mechanical strength. However, exposed collagen on the tissue induces blood coagulation, and low hemocompatibility is a major obstacle to its vascular application. Here we report that freeze-drying and ethanol treatment effectively modify collagen fiber structure and drastically reduce blood coagulation on the graft surface without exogenous chemical modification. Decellularized carotid artery of ostrich was treated with freeze-drying and ethanol solution at concentrations ranging between 5 and 99.5 %. Collagen fiber distance in the graft was narrowed by freeze-drying, and the non-helical region increased by ethanol treatment. Although in vitro blood coagulation pattern was similar on the grafts, platelet adhesion on the grafts was largely suppressed by freeze-drying and ethanol treatments. Ex vivo blood circulation tests also indicated that the adsorption of platelets and Von Willebrand Factor was largely reduced to approximately 80 % by ethanol treatment. These results indicate that structural modification of collagen fibers in decellularized tissue reduces blood coagulation on the surface by inhibiting platelet adhesion.

Microengineering 3D Collagen Matrices with Tumor-Mimetic Gradients in Fiber Alignment.

Collagen fibers in the 3D tumor microenvironment (TME) exhibit complex alignment landscapes that are critical in directing cell migration through a process called contact guidance. Previous in vitro work studying this phenomenon has focused on quantifying cell responses in uniformly aligned environments. However, the TME also features short-range gradients in fiber alignment that result from cell-induced traction forces. Although the influence of graded biophysical taxis cues is well established, cell responses to physiological alignment gradients remain largely unexplored. In this work, fiber alignment gradients in biopsy samples are characterized and recreated using a new microfluidic biofabrication technique to achieve tunable sub-millimeter to millimeter scale gradients. This study represents the first successful engineering of continuous alignment gradients in soft, natural biomaterials. Migration experiments on graded alignment show that HUVECs exhibit increased directionality, persistence, and speed compared to uniform and unaligned fiber architectures. Similarly, patterned MDA-MB-231 aggregates exhibit biased migration toward increasing fiber alignment, suggesting a role for alignment gradients as a taxis cue. This user-friendly approach, requiring no specialized equipment, is anticipated to offer new insights into the biophysical cues that cells interpret as they traverse the extracellular matrix, with broad applicability in healthy and diseased tissue environments.

The influence of immediate occlusal loading on micro/nano-structure of peri-implant jaw bone in rats.

PURPOSE: The objective of the present study was to ascertain the effect of immediate occlusal loading after implant placement on osseointegration and the micro/nanostructure of the surrounding bone. METHODS: After extraction of a rat maxillary right second molar, an implant was placed immediately with initial fixation (2 N< ). The implants were placed to avoid occlusal loading due to mastication, and in the loaded group, a superstructure was fabricated and subjected to occlusal loading. Bone morphometry, collagen fiber anisotropy, and biological apatite (BAp) crystallite alignment were quantitatively evaluated in both groups after extraction and fixation of the jaw bone at Days 7 and 21 after surgery. RESULTS: Osseointegration was observed in both groups. Bone morphometry showed significant differences in bone volume, trabecular number, trabecular thickness and bone mineral density (BMD) at Days 21 postoperatively (P < 0.05). A significant difference was also found in the trabecular separation at Days 7 postoperatively (P < 0.05). In the evaluation of collagen fiber anisotropy, collagen fiber bundles running differently from the existing bone were observed in both groups. In terms of BAp crystallite alignment, a specific structure was observed in the reconstructed new bone after implantation, and preferential orientation of BAp crystallite alignment was observed in the longitudinal direction of the implants in the Day 21 postoperative loaded group. CONCLUSION: When sufficient initial fixation is achieved at the time of dental implant placement, then the applied masticatory load may contribute to rapidly achieving not only bone volume, but also adequate bone quality after implant placement.

Collagen and elastic fibers assessment of the human heart valves for age estimation in Thais using image analysis.

The study investigated the relationship between the histological compositions of the tricuspid, pulmonary, mitral, and aortic valves, and age. All 85 fresh human hearts were obtained with an age range between 20 and 90 years. The central area of the valves was conducted to analyze the density of collagen and elastic fibers by using an image analysis program. Neural network function in MATLAB was used for classification data and accuracy test of the age predictive model. Overall, a gradual increase in the density of collagen and elastic fibers was demonstrated with age in all valve types. The pulmonary valve cusps had the least density of collagen and elastic contents, whereas the most dense of collagen was found in the mitral leaflets. A similarity was noted for the elastic fibers in the tricuspid, mitral, and aortic valves. The highest correlation between the collagen (r = 0.629) and elastic fibers (r = 0.713) and age was found in the noncoronary cusp of the aortic valve. The established predictive equations using collagen and elastic fibers in the noncoronary cusp provided the standard error of ± 14.0 and 12.5 years, respectively. A 60.9% of accuracy was found in all age groups using collagen, while accuracy in elastic fibers showed 70.0% in the classification process using the neural networks. The current study provided additional data regarding age-associated changes of collagen and elastic fibers in the human heart valves in Thais and the benefits and application in age forensic identification.

Warming Yang Promoting Blood Circulation and Diuresis Alleviates Myocardial Damage by Inhibiting Collagen Fiber and Myocardial Fibrosis and Attenuating Mitochondria Signaling Pathway Mediated Apoptosis in Chronic Heart Failure Rats.

Warming Yang promoting blood circulation and diuresis (WYPBD) has been proven effective in treating some diseases. This study aimed to evaluate therapeutic effect of WYPBD in treating chronic heart failure (CHF). CHF rats were established by intraperitoneally injecting doxorubicin (DOX). Therapeutic effects of WYPBD on cardiac function and hemodynamic parameters of myocardial tissues were analyzed. Collagen fiber production and myocardial fibrosis were evaluated. Transcriptions of COL1A1 gene, COL3A1 gene, and TGFB1 gene were evaluated with RT-PCR. Expression of BNP, AVP, PARP, caspase-3, and Bcl-2 in myocardial tissues were evaluated. TUNEL assay was used to identify apoptosis of cardiomyocytes. WYPBD alleviated degree of myocardial hypertrophy in CHF rats compared to the rats in CHF model group (P < 0.05). WYPBD significantly improved cardiac hemodynamics (increased LVEF and LVSF) of CHF rats compared to rats in the CHF model group (P < 0.05). WYPBD protected myocardial structure and inhibited collagen fiber production in myocardial tissues of CHF rats. WYPBD markedly decreased myocardial fibrosis mediators (Col1α, Col3α, TGF-ß1) transcription in myocardial tissues of CHF rats compared to rats in CHF model group (P < 0.05). WYPBD significantly reduced BNP and AVP expression in myocardial tissues of CHF rats compared to rats in the CHF model group (P < 0.05). WYPBD markedly reduced the expression of PRAP and caspase-3, and increased Bcl-2 expression in myocardial tissues of CHF rats compared to rats in the CHF model group (P < 0.05). In conclusion, WYPBD alleviated CHF myocardial damage by inhibiting collagen fiber and myocardial fibrosis, attenuating apoptosis associated with the mitochondria signaling pathway of cardiomyocytes.

Biomimetic Dual-Network Collagen Fibers with Porous and Mechanical Cues Reconstruct Neural Stem Cell Niche via AKT/YAP Mechanotransduction after Spinal Cord Injury.

Tissue engineering scaffolds can mediate the maneuverability of neural stem cell (NSC) niche to influence NSC behavior, such as cell self-renewal, proliferation, and differentiation direction, showing the promising application in spinal cord injury (SCI) repair. Here, dual-network porous collagen fibers (PCFS) are developed as neurogenesis scaffolds by employing biomimetic plasma ammonia oxidase catalysis and conventional amidation cross-linking. Following optimizing the mechanical parameters of PCFS, the well-matched Young's modulus and physiological dynamic adaptability of PCFS (4.0 wt%) have been identified as a neurogenetic exciter after SCI. Remarkably, porous topographies and curving wall-like protrusions are generated on the surface of PCFS by simple and non-toxic CO2 bubble-water replacement. As expected, PCFS with porous and matched mechanical properties can considerably activate the cadherin receptor of NSCs and induce a series of serine-threonine kinase/yes-associated protein mechanotransduction signal pathways, encouraging cellular orientation, neuron differentiation, and adhesion. In SCI rats, implanted PCFS with matched mechanical properties further integrated into the injured spinal cords, inhibited the inflammatory progression and decreased glial and fibrous scar formation. Wall-like protrusions of PCFS drive multiple neuron subtypes formation and even functional neural circuits, suggesting a viable therapeutic strategy for nerve regeneration and functional recovery after SCI.

A novel complex coupling agent for enhancing the compatibility between collagen fiber and natural rubber: A utilization strategy for leather wastes.

Leather shavings are generated as solid waste in the leather industry and may cause environmental pollution if not disposed judiciously. These solid wastes, primarily composed of collagen fibers (CFs), can be recycled as biomass composites. However, CFs are incompatible with natural rubber (NR) due to its hydrophilicity. Conventionally, the compatibility has been improved by utilizing silane coupling agents (SCAs) along with a large number of organic solvents, which further contribute to environmental pollution. In this study, we developed a novel complex coupling agent (CCA) to enhance the compatibility between CF and NR. The CCA was synthesized through a coordination reaction between Cr(III) and α-methacrylic acid (MAA). Cr(III) in the coupling agent coordinates with the active groups in CFs, while the unsaturated double bonds in MAA facilitate covalent crosslinking between the CCA and NR, improving compatibility. The coordination bonding between CF and NR exhibits strong interfacial interaction, endowing the composites with desirable mechanical properties. Moreover, the proposed method is an economical and green approach that can be used to synthesize CF-based composites without requiring organic solvents. Herein, a strategy promoted sustainable development in the leather industry has been established.

Structural parameters defining distribution of collagen fiber directions in human carotid arteries.

Collagen fiber arrangement is decisive for constitutive description of anisotropic mechanical response of arterial wall. In this study, their orientation in human common carotid artery was investigated using polarized light microscopy and an automated algorithm giving more than 4·106 fiber angles per slice. In total 113 slices acquired from 18 arteries taken from 14 cadavers were used for fiber orientation in the circumferential-axial plane. All histograms were approximated with unimodal von Mises distribution to evaluate dominant direction of fibers and their concentration parameter. 10 specimens were analyzed also in circumferential-radial and axial-radial planes (2-4 slices per specimen in each plane); the portion of radially oriented fibers was found insignificant. In the circumferential-axial plane, most specimens showed a pronounced unimodal distribution with angle to circumferential direction µ = 0.7° ± 9.4° and concentration parameter b = 3.4 ± 1.9. Suitability of the unimodal fit was confirmed by high values of coefficient of determination (mean R2 = 0.97, median R2 = 0.99). Differences between media and adventitia layers were not found statistically significant. The results are directly applicable as structural parameters in the GOH constitutive model of arterial wall if the postulated two fiber families are unified into one with circumferential orientation.

Early delivery of human umbilical cord mesenchymal stem cells improves healing in a rat model of Achilles tendinopathy.

Objective: This study aimed to explore the efficacy and optimal delivery time of human umbilical cord mesenchymal stem cells (hUC-MSCs) in treating collagenase-induced Achilles tendinopathy. Methods: Achilles tendinopathy in rats at early or advanced stages was induced by injecting collagenase I into bilateral Achilles tendons. A total of 28 injured rats were injected with a hUC-MSC solution or normal saline into bilateral tendons twice and sampled after 4 weeks for histological staining, gene expression analysis, transmission electron microscope assay and biomechanical testing analysis. Results: The results revealed better histological performance and a larger collagen fiber diameter in the MSC group. mRNA expression of TNF-α, IL-1ß and MMP-3 was lower after MSC transplantation. Early MSC delivery promoted collagen I and TIMP-3 synthesis, and strengthened tendon toughness. Conclusion: hUC-MSCs demonstrated a therapeutic effect in treating collagenase-induced Achilles tendinopathy, particularly in the early stage of tendinopathy.

Electron Beam-Modified Collagen Type I Fibers: Synthesis and Characterization of Mechanical Response.

Ten MeV electron beam treatment facilitates a biomimetic introduction of cross-links in collagenous biopolymer systems, modifying their viscoelastic properties, mechanical stability, and swelling behavior. For reconstituted collagen type I fibers, electron-induced cross-linking opens up new perspectives regarding future biomedical applications in terms of tissue and ligament engineering. We demonstrate how electron irradiation affects stiffness both in low-strain regimes and in postyield regimes of biocompatible reconstituted rat tail collagen type I fibers. Stress-strain tests show a dose-dependent increase in modulus in the nonlinear elastic response, indicating a central role of induced cross-links in mechanical stability. Environmental scanning electron microscopy after fiber rupture reveals aligned distributed collagen fibril domains under the fiber surface for as-prepared fibers, accompanied by a ductile fracture behavior, whereas, in tensile tests imaged by light microscopy after 10 MeV electron treatment, isotropic network topologies are observed until the occurrence of a brittle type of rupture. Based on the biomimicry of the process, these findings might pave the way for a novel type of synthesis of tailored tendon or ligament substitutes.

Dual green hemostatic sponges constructed by collagen fibers disintegrated from Halocynthia roretzi by a shortcut method.

Recently, biomacromolecules have received considerable attention in hemostatic materials. Collagen, an ideal candidate for hemostatic sponges due to its involvement in the clotting process, has been facing challenges in extraction from raw materials, which is time-consuming, expensive, and limited by cultural and religious restrictions associated with traditional livestock and poultry sources. To address these issues, this study explored a new shortcut method that using wild Halocynthia roretzi (HR), a marine fouling organism, as a raw material for developing HR collagen fiber sponge (HRCFs), which employed urea to disrupt hydrogen bonds between collagen fiber aggregates. This method simplifies traditional complex manufacturing processes while utilized marine waste, thus achieving dual green in terms of raw materials and manufacturing processes. FTIR results confirmed that the natural triple-helical structure of collagen was preserved. HRCFs exhibit a blood absorption ratio of 2000-3500 %, attributed to their microporous structure, as demonstrated by kinetic studies following a capillary model. Remarkably, the cytotoxicity and hemolysis ratio of HRCFs are negligible. Furthermore, during in vivo hemostasis tests using rabbit ear and kidney models, HRCFs significantly reduce blood loss and shorten hemostasis time compared to commercial gelatin sponge and gauze, benefiting from the capillary effect and collagen's coagulation activity. This study provides new insights into the design of collagen-based hemostatic biomaterials, especially in terms of both raw material and green manufacturing processes.

Strain-mode-specific mechanical testing and the interpretation of bone adaptation in the deer calcaneus.

The artiodactyl (deer and sheep) calcaneus is a model that helps in understanding how many bones achieve anatomical optimization and functional adaptation. We consider how the dorsal and plantar cortices of these bones are optimized in quasi-isolation (the conventional view) versus in the context of load sharing along the calcaneal shaft by "tension members" (the plantar ligament and superficial digital flexor tendon). This load-sharing concept replaces the conventional view, as we have argued in a recent publication that employs an advanced analytical model of habitual loading and fracture risk factors of the deer calcaneus. Like deer and sheep calcanei, many mammalian limb bones also experience prevalent bending, which seems problematic because the bone is weaker and less fatigue-resistant in tension than compression. To understand how bones adapt to bending loads and counteract deleterious consequences of tension, it is important to examine both strain-mode-specific (S-M-S) testing (compression testing of bone habitually loaded in compression; tension testing of bone habitually loaded in tension) and non-S-M-S testing. Mechanical testing was performed on individually machined specimens from the dorsal "compression cortex" and plantar "tension cortex" of adult deer calcanei and were independently tested to failure in one of these two strain modes. We hypothesized that the mechanical properties of each cortex region would be optimized for its habitual strain mode when these regions are considered independently. Consistent with this hypothesis, energy absorption parameters were approximately three times greater in S-M-S compression testing in the dorsal/compression cortex when compared to non-S-M-S tension testing of the dorsal cortex. However, inconsistent with this hypothesis, S-M-S tension testing of the plantar/tension cortex did not show greater energy absorption compared to non-S-M-S compression testing of the plantar cortex. When compared to the dorsal cortex, the plantar cortex only had a higher elastic modulus (in S-M-S testing of both regions). Therefore, the greater strength and capacity for energy absorption of the dorsal cortex might "protect" the weaker plantar cortex during functional loading. However, this conventional interpretation (i.e., considering adaptation of each cortex in isolation) is rejected when critically considering the load-sharing influences of the ligament and tendon that course along the plantar cortex. This important finding/interpretation has general implications for a better understanding of how other similarly loaded bones achieve anatomical optimization and functional adaptation.

Runx2 heterozygosity alters homeostasis of the periodontal complex.

BACKGROUND AND OBJECTIVE: Haploinsufficiency of Runx2 (Runx2+/- ) causes dental anomalies. However, little is known about the involvement of Runx2 in the maintenance of dentin, cementum, and the periodontal ligament (PDL) during adulthood. This study aimed to observe the effects of Runx2+/- on homeostasis of the periodontal complex. MATERIALS AND METHODS: A total of 14 three-month-old Runx2+/- mice and their wild-type littermates were examined using micro-computed tomography, histology, and immunohistochemistry. Phenotypic alterations in the dentin, cementum, and PDL were characterized and quantified. RESULTS: Haploinsufficiency of Runx2 caused cellular changes in the PDL space including reduction of cell proliferation and apoptosis, and irregular attachment of the collagen fibers in the PDL space into the cementum. Absence of continuous thickness of cementum was also observed in Runx2+/- mice. CONCLUSION: Runx2 is critical for cementum integrity and attachment of periodontal fibers. Because of its importance to cementum homeostasis, Runx2 is essential for homeostasis of periodontal complex.