Collagenous Bone Matrix Research Articles

Heterogeneous decellularized bone collagen matrix in oral treatment

Heterogeneous decellularized bone collagen matrix in oral treatment

Phosphate Ion-Responsive and Calcium Peroxide-Based Nanomedicine for Bone-Targeted Treatment of Breast Cancer Bone Metastasis.

The treatment of breast cancer bone metastasis is an unresolved clinical challenge, mostly because currently therapeutic approaches cannot simultaneously block the tumor growth and repair the osteolytic bone injuries at the metastatic site. Herein, the study develops a novel nanomedicine to treat breast cancer bone metastasis. The nanomedicine is based on phosphate ion-responsive and calcium peroxide-based nanoparticles carrying the bone-targeting agent zoledronic acid on the surface and loaded with the photosensitizer indocyanine green. Following intravenous administration to a mouse model of breast cancer bone metastasis, the nanoparticles efficiently accumulate at the bone metastasis site, react with free phosphate ions, and form hydroxyapatite nanoaggregates and O2, while releasing the photosensitizer. Hydroxyapatite nanoaggregates elicit the remineralization of the collagenous bone matrix and trigger tumor cell apoptosis. Upon irradiating tumor-bearing legs with an 808nm laser source, the O2 and free photosensitizer produced 1O2 by the reaction of the nanoparticles with phosphate ions, further boosting the anti-tumor effect. Tumor killing hampers the vicious cycle at the site of bone metastasis, translating to osteolysis blockade and further encouraging the remineralization of bone matrix. This work sheds light on the development of a novel, safe, and efficient approach for the treatment of breast cancer bone metastasis.

Effect of collagen fibril orientation on the anisotropic properties of peri-implant bone.

In orthopedic and dental surgery, the implantation of biomaterials within the bone to restore the integrity of the treated organ has become a standard procedure. Their long-term stability relies on the osseointegration phenomena, where bone grows onto and around metallic implants, creating a bone-implant interface. Bone is a highly hierarchical material that evolves spatially and temporally during this healing phase. A deeper understanding of its biomechanical characteristics is needed, as they are determinants for surgical success. In this context, we propose a multiscale homogenization model to evaluate the effective elastic properties of bone as a function of the distance from the implant, based on the tissue's structure and composition at lower scales. The model considers three scales: hydroxyapatite foam (nanoscale), ultrastructure (microscale), and tissue (mesoscale). The elastic properties and the volume fraction of the elementary constituents of bone matrix (mineral, collagen, and water), the orientation of the collagen fibril relative to the implant surface, and the mesoscale porosity constitute the input data of the model. The effect of a spatiotemporal variation in the collagen fibrils' orientation on the bone anisotropic properties in the proximity of the implant was investigated. The findings revealed a strong variation of the components of the effective elasticity tensor of the bone as a function of the distance from the implant. The effective elasticity appears to be primarily sensitive to the porosity (mesoscale) rather than to the collagen fibrils' orientation (sub-micro scale). However, the orientation of the fibrils has a significant influence on the isotropy of the bone. When analyzing the symmetry properties of the effective elasticity tensor, the ratio between the isotropic and hexagonal components is determined by a combination of the porosity and the fibrils' orientation. A decrease in porosity leads to a decrease in bone isotropy and, in turn, an increase in the impact of the fibrils' orientation. These results demonstrate that the collagen fibril orientation should be taken into account to properly describe the effective elastic anisotropy of bone at the organ scale.

Association of serum osteocalcin with bone microarchitecture and muscle mass in Beijing community-dwelling postmenopausal women.

Osteoporosis is a systemic skeletal disease with increasing bone fragility and prone to fracture. Osteocalcin (OC), as the most abundant non collagen in bone matrix, has been extensively used in clinic as a biochemical marker of osteogenesis. Two forms of OC were stated on circulation, including carboxylated osteocalcin (cOC) and undercarboxylated osteocalcin (ucOC). OC was not only involved in bone mineralization, but also in the regulation of muscle function. This study explored the relationship between serum OC, cOC, ucOC levels and bone mineral density (BMD), bone microarchitecture, muscle mass and physical activity in Chinese postmenopausal women. 216 community-dwelling postmenopausal women were randomized enrolled. All subjects completed biochemical measurements, including serum β-isomer of C-terminal telopeptides of type I collagen (β-CTX), N-terminal propeptide of type 1 procollagen (P1NP), alkaline phosphatase (ALP), OC, cOC and ucOC. They completed X-ray absorptiometry (DXA) scan to measure BMD, appendicular lean mass (ALM) and trabecular bone score (TBS). They completed high resolution peripheral quantitative CT (HR-pQCT) to assess peripheral bone microarchitectures. Serum OC, cOC and ucOC were elevated in osteoporosis postmenopausal women. In bone geometry, serum ucOC was positively related with total bone area (Tt.Ar) and trabecular area(Tb.Ar). In bone volumetric density, serum OC and ucOC were negatively associated with total volume bone mineral density (Tt.vBMD) and trabecular volume bone mineral density (Tb.vBMD). In bone microarchitecture, serum OC and ucOC were negatively correlative with Tb.N and Tb.BV/TV, and were positively correlated with Tb.Sp. Serum OC and ucOC were positively associated with Tb.1/N.SD. Serum OC was negatively related with Tb.Th. Serum ucOC was positively associated with ALM. The high level of serum OC was the risk factor of osteoporosis. ALM was the protective factor for osteoporosis. All forms of serum OC were negatively associated with BMD. Serum OC and ucOC mainly influenced microstructure of trabecular bone in peripheral skeletons. Serum ucOC participated in modulating both bone microstructure and muscle mass.

Silver─Gallium Nano‐Amalgamated Particles as a Novel, Biocompatible Solution for Antibacterial Coatings

AbstractBacterial infections account for countless deaths globally. Antibiotics are the primary countermeasure; however, the alarming spread of antibiotic‐resistant strains necessitates alternative solutions. Silver and silver compounds have emerged as promising antibacterial agents. However, issues related to cytotoxicity and genotoxicity of silver remain concern. To overcome these challenges, this proposes an easy‐to‐control and straightforward method to synthesize novel Silver─gallium (Ag─Ga) nano‐amalgamated particles. Gallium liquid metal (GaLM) is used to facilitate the galvanic deposition of silver nanocrystals (Ag) on oxide layer. The GaLM not only serves as a carrier for silver through the galvanic replacement process, but also provides a controlled‐release mechanism for silver, in this way improving biocompatibility, reducing inflammation, and stimulating bone growth. Notably, Ag─Ga suspensions can be conveniently deposited by spray‐coating on a range of devices and material surfaces, effectively eliminating pathogenic bacteria with efficacy comparable to that of silver ions. In vivo studies in rat models affirm the antibacterial capabilities, especially against methicillin‐resistant Staphylococcus aureus and Escherichia coli, when placed on implants such as titanium rods and magnesium discs. Furthermore, Ag─Ga promotes bone matrix formation and collagen growth without eliciting an inflammatory response, indicating a major promise for coatings on a wide variety of biomedical devices and materials.

Assessment of Osteoporosis at the Lumbar Spine Using Ultrashort Echo Time Magnetization Transfer (UTE-MT) MRI.

Bone collagen-matrix contributes to the mechanical properties of bone by imparting tensile strength and elasticity, which can be indirectly quantified by ultrashort echo time magnetization transfer ratio (UTE-MTR) to assess osteoporosis. To evaluate osteoporosis at the human lumbar spine using UTE-MTR. Prospective. One hundred forty-eight-volunteers (age-range, 50-85; females, N = 90), including 81-normal bone density, 35-osteopenic, and 32-osteoporotic subjects. Ten additional healthy volunteers were recruited to study the intrasession reproducibility of the UTE-MT. 3T/UTE-MT, short repetition-time adiabatic inversion recovery prepared UTE (STAIR-UTE), and iterative decomposition of water-and-fat with echo-asymmetry and least-squares estimation (IDEAL-IQ). Fracture risk was calculated using Fracture-Risk-Assessment-Tool (FRAX). Region-of-interests (ROIs) were delineated on the trabecular area in the maps of bone-mineral-density, UTE-MTR, collagen-bound water proton-fraction (CBWPF), and bone-marrow fat fraction (BMFF). Linear-regression and Bland-Altman analysis were performed to assess the reproducibility of UTE-MTR measurements in the different scans. UTE-MTR and BMFF were correlated with bone-mineral-density using Pearson's regression and with FRAX scores using nonlinear regression. The abilities of UTE-MTR, CBWPF, and BMFF to discriminate between the three patient subgroups were evaluated using receiver-operator-characteristic (ROC) analysis and area-under-the-curve (AUC). Decision-curve-analysis (DCA) and clinical-impact curves were used to evaluate the value of UTE-MTR in clinical diagnosis. The DeLong test was used to compare the ROC curves. P-value <0.05 was considered statistically significant. Excellent reproducibility was obtained for the UTE-MT measurements. UTE-MTR strongly correlated with bone-mineral-density (r = 0.76) and FRAX scores (r = -0.77). UTE-MTR exhibited higher AUCs (≥0.723) than BMFF, indicating its superior ability to distinguish between the three patient subgroups. The DCA and clinical-impact curves confirmed the diagnostic value of UTE-MTR. UTE-MTR and CBWPF showed similar performance in correlation with bone-mineral-density and cohort classification. UTE-MTR strongly correlates with bone-mineral-density and FRAX and shows great potential in distinguishing between normal, osteopenic, and osteoporotic subjects. 1 TECHNICAL EFFICACY: Stage 2.

Socket Preservation after Tooth Extraction: Particulate Autologous Bone vs. Deproteinized Bovine Bone.

The technique of socket preservation after tooth extraction allows for less volumetric decrease after tooth extraction. The aim of this retrospective study was to evaluate differences between alveolar socket preservation performed with deproteinized bovine bone graft and autologous particulate bone graft taken from the mandibular ramus. This retrospective study enrolled a total of 21 consecutive patients. A total of 11 patients underwent socket preservation with deproteinized bovine bone graft and collagen matrix (group A), and 10 patients underwent socket preservation performed with particulate autologous bone taken from the mandibular ramus and collagen matrix (group B). All patients received cone beam computed tomography (CBCT) before socket preservation and after four months. Alveolar bone width (ABW) values and alveolar bone height (ABH) values were measured at the first and second CBCT, and the reduction of the values in the two groups was compared. Statistical analysis was performed using Student's t-test for independent variables, and p values < 0.05 were considered statistically significant. There were no statistically significant differences between ABW reduction of group A and ABW reduction of group B (t-test value p = 0.28). There were no statistically significant differences between ABH reduction of group A and ABH reduction of group B (t-test value p = 0.10). In this retrospective study, no statistical differences were found between the group that received autologous particulate bone compared to the group that received deproteinized bovine bone in socket preservation.

Biomimetic Remineralized Three-Dimensional Collagen Bone Matrices with an Enhanced Osteostimulating Effect.

Bone grafts with a high potential for osseointegration, capable of providing a complete and effective regeneration of bone tissue, remain an urgent and unresolved issue. The presented work proposes an approach to develop composite biomimetic bone material for reconstructive surgery by deposition (remineralization) on the surface of high-purity, demineralized bone collagen matrix calcium phosphate layers. Histological and elemental analysis have shown reproduction of the bone tissue matrix architectonics, and a high-purity degree of the obtained collagen scaffolds; the cell culture and confocal microscopy have demonstrated a high biocompatibility of the materials obtained. Adsorption spectroscopy, scanning electron microscopy, microcomputed tomography (microCT) and infrared spectroscopy, and X-ray diffraction have proven the efficiency of the deposition of calcium phosphates on the surface of bone collagen scaffolds. Cell culture and confocal microscopy methods have shown high biocompatibility of both demineralized and remineralized bone matrices. In the model of heterotopic implantation in rats, at the term of seven weeks, an intensive intratrabecular infiltration of calcium phosphate precipitates, and a pronounced synthetic activity of osteoblast remodeling and rebuilding implanted materials, were revealed in remineralized bone collagen matrices in contrast to demineralized ones. Thus, remineralization of highly purified demineralized bone matrices significantly enhanced their osteostimulating ability. The data obtained are of interest for the creation of new highly effective osteoplastic materials for bone tissue regeneration and augmentation.

Icariin: A Promising Natural Product in Biomedicine and Tissue Engineering.

Among scaffolds used in tissue engineering, natural biomaterials such as plant-based materials show a crucial role in cellular function due to their biocompatibility and chemical indicators. Because of environmentally friendly behavior and safety, green methods are so important in designing scaffolds. A key bioactive flavonoid of the Epimedium plant, Icariin (ICRN), has a broad range of applications in improving scaffolds as a constant and non-immunogenic material, and in stimulating the cell growth, differentiation of chondrocytes as well as differentiation of embryonic stem cells towards cardiomyocytes. Moreover, fusion of ICRN into the hydrogel scaffolds or chemical crosslinking can enhance the secretion of the collagen matrix and proteoglycan in bone and cartilage tissue engineering. To scrutinize, in various types of cancer cells, ICRN plays a decisive role through increasing cytochrome c secretion, Bax/Bcl2 ratio, poly (ADP-ribose) polymerase as well as caspase stimulations. Surprisingly, ICRN can induce apoptosis, reduce viability and inhibit proliferation of cancer cells, and repress tumorigenesis as well as metastasis. Moreover, cancer cells no longer grow by halting the cell cycle at two checkpoints, G0/G1 and G2/M, through the inhibition of NF-κB by ICRN. Besides, improving nephrotoxicity occurring due to cisplatin and inhibiting multidrug resistance are the other applications of this biomaterial.

Evaluation of the regenerative capacity of stem cells combined with bone graft material and collagen matrix using a rabbit calvarial defect model.

The purpose of this study was to evaluate the regenerative capacity of stem cells combined with bone graft material and a collagen matrix in rabbit calvarial defect models according to the type and form of the scaffolds, which included type I collagen matrix and synthetic bone. Mesenchymal stem cells (MSCs) were obtained from the periosteum of participants. Four symmetrical 6-mm-diameter circular defects were made in New Zealand white rabbits using a trephine drill. The defects were grafted with (1) group 1: synthetic bone (β-tricalcium phosphate/hydroxyapatite [β-TCP/HA]) and 1×105 MSCs; (2) group 2: collagen matrix and 1×105 MSCs; (3) group 3: β-TCP/HA, collagen matrix covering β-TCP/HA, and 1×105 MSCs; or (4) group 4: β-TCP/HA, chipped collagen matrix mixed with β-TCP/HA, and 1×105 MSCs. Cellular viability and cell migration rates were analyzed. Uneventful healing was achieved in all areas where the defects were made at 4 weeks, and no signs of infection were identified during the healing period or at the time of retrieval. New bone formation was more evident in groups 3 and 4 than in the other groups. A densitometric analysis of the calvarium at 8 weeks post-surgery showed the highest values in group 3. This study showed that the highest regeneration was found when the stem cells were applied to synthetic bone along with a collagen matrix.

Effects of oral losartan administration on homeostasis of articular cartilage and bone in a rabbit model

Background and aimsPrevious work has shown that oral losartan can enhance microfracture-mediated cartilage repair in a rabbit osteochondral defect injury model. In this study, we aimed to determine whether oral losartan would have a detrimental effect on articular cartilage and bone homeostasis in the uninjured sides. MethodsNew Zealand rabbits were divided into 4 groups including normal uninjured (Normal), contralateral uninjured side of osteochondral defect (Defect), osteochondral defect plus microfracture (Microfracture) and osteochondral defect plus microfracture and losartan oral administration (10 mg/kg/day) (Losartan). Rabbits underwent different surgeries and treatment and were sacrificed at 12 weeks. Both side of the normal group and uninjured side of treatment groups tibias were harvested for Micro-CT and histological analysis for cartilage and bone including H&E staining, Herovici's staining (bone and cartilage) Alcian blue and Safranin O staining (cartilage) as well as immunohistochemistry of losartan related signaling pathways molecules for both cartilage and bone. ResultsOur results showed losartan oral treatment at 10 mg/kg/day slightly increase Alcian blue positive matrix as well as decrease collagen type 3 in articular cartilage while having no significant effect on articular cartilage structure, cellularity, and other matrix. Losartan treatment also did not affect angiotensin receptor type 1 (AGTR1), angiotensin receptor type 2 (AGTR2) and phosphorylated transforming factor β1 activated kinase 1 (pTAK1) expression level and pattern in the articular cartilage. Furthermore, losartan treatment did not affect microarchitecture of normal cancellous bone and cortical bone of tibias compared to normal and other groups. Losartan treatment slightly increased osteocalcin positive osteoblasts on the surface of cancellous bone and did not affect bone matrix collagen type 1 content and did not change AGTR1, AGTR2 and pTAK1 signal molecule expression. ConclusionOral losartan used as a microfracture augmentation therapeutic does not have significant effect on uninjured articular cartilage and bone based on our preclinical rabbit model. These results provided further evidence that the current regimen of using losartan as a microfracture augmentation therapeutic is safe with respect to bone and cartilage homeostasis and support clinical trials for its application in human cartilage repair.

Aluminum intake in the neonatal phase disrupts endochondral ossification in rodents

ObjectiveThis study evaluated the effects of aluminum (Al) intake on endochondral ossification during the neonatal phase. MethodTwelve male newborn Gerbils (Meriones unguiculatus) were randomly divided into control (C) and aluminum (Al) groups (n = 6 animals/group). From the 1st to 15th day of life, gerbils received an AlCl3 solution (10 mg/kg/day) via gavage. The control group received only the saline solution. On the 16th day, their tibias were processed for paraffin embedding and were submitted to histomorphometric, histochemical, and immunohistochemical analyses. ResultsIn the epiphyseal cartilage Al did not affect the proteoglycan content or cell proliferation; however, it increased matrix metalloprotease-2 (MMP-2) immunostaining and the hypertrophic layer thickness. In bone, Al decreased trabeculae number, trabecular width, cortical bone width, and proliferation. Furthermore, the relative frequency of bone matrix and fibrillar collagen decreased 3.9% and 16.2%, respectively. The number of osteoclasts and osteocalcin digital optical density (D.O.D) remained the same. ConclusionThe results suggest that Al intake during the neonatal period impairs endochondral ossification by affecting epiphyseal cartilage and bone architecture.

Charge balancing stabilized apatite enter into collagen fibers by osmotic pressure to induce the formation of intrafibrillar mineralization

Intrafibrillar mineralized collagen is the main form of natural mineralized collagen in bone matrix. However, the mechanism involved in the intrafibrillar mineralization is still unclear. Here, by measuring the changes of Zeta potential and adjusting the osmotic pressure of collagen fibers to study the mechanism of intrafibrillar mineralization. The changes in zeta potential and reduction in size during the formation of amorphous calcium phosphate (ACP) after adding negatively charged polyacrylic acid (PAA) and positively charged cationicpolyacrylamide (CPAM) indicate that the stabilization mechanism of ACP induced by polyelectrolyte compound is charge balance. Then, osmotic pressure pressures charge balancing stabilized ACP into collagen fibers to induce intrafibrillar mineralization. This discovery provides basis for further understanding the intrafibrillar mineralization, preparing new biomimetic mineralized materials and promoting the development of tissue engineering.

Degradable smart composite foams for bone regeneration

Degradable scaffolds with high porosity, certain mechanical and shape memory properties and biocompatibility are ideal materials in the field of bone tissue engineering for minimally invasive surgical implantation methods. In this study, we prepared porous scaffolds using hydrophilic polyethylene glycol and degradable polycaprolactone as raw materials and calcium citrate/amorphous calcium phosphate as hybrid particles, via sequential gas foaming, salt leaching and freeze drying methods. The fabricated bone scaffold exhibited adjustable mechanical properties and pore structure, with high shape fixation (>94.5%) and shape recovery (>87%) in thermal cycling and excellent shape memory properties under simulated body fluid immersion near body temperature. Moreover, in cell proliferation and live/dead cell activity assay experiments, the scaffolds promoted the proliferation of mesenchymal stem cells (MSCs). Immunofluorescence staining assay experiments further showed that the scaffolds had strong expressions of human type Ⅰ collagen (Col I) and alkaline phosphatase (ALP) in bone matrix. The material is expected to be a potential alternative material for bone tissue engineering.

Combining Bone Collagen Matrix with hUC-MSCs for Application to Alveolar Process Cleft in a Rabbit Model.

Most materials used clinically for filling severe bone defects either cannot induce bone re-generation or exhibit low bone conversion, therefore, their therapeutic effects are limited. Human umbilical cord mesenchymal stem cells (hUC-MSCs) exhibit good osteoinduction. However, the mechanism by which combining a heterogeneous bone collagen matrix with hUC-MSCs to repair the bone defects of alveolar process clefts remains unclear. A rabbit alveolar process cleft model was established by removing the bone tissue from the left maxillary bone. Forty-eight young Japanese white rabbits (JWRs) were divided into normal, control, material and MSCs groups. An equal volume of a bone collagen matrix alone or combined with hUC-MSCs was implanted in the defect. X-ray, micro-focus computerized tomography (micro-CT), blood analysis, histochemical staining and TUNEL were used to detect the newly formed bone in the defect area at 3 and 6months after the surgery. The bone formation rate obtained from the skull tissue in MSCs group was significantly higher than that in control group at 3months (P < 0.01) and 6months (P < 0.05) after the surgery. The apoptosis rate in the MSCs group was significantly higher at 3months after the surgery (P < 0.05) and lower at 6months after the surgery (P < 0.01) than those in the normal group. Combining bone collagen matrix with hUC-MSCs promoted the new bone regeneration in the rabbit alveolar process cleft model through promoting osteoblasts formations and chondrocyte growth, and inducing type I collagen formation and BMP-2 generation.

Commentaries on Viewpoint: Fragile bones of elite cyclists: to treat or not to treat?

Commentaries on Viewpoint: Fragile bones of elite cyclists: to treat or not to treat?

Diabetes mellitus and osteoporosis: pathogenetic relationship and current principles of treatment

Diabetes mellitus (DM) is a well known risk factor for osteoporosis and an increased risk of fractures. A lot of data has been published about the relationship between diabetes and bone health. DM type 1 and DM type 2 have different effects on bone mineral density (BMD). The central link in pathogenesis of bone fragility in patients with DM type 1 is a violation of the activity and gifferentiation of osteoblasts. On the contrary, hyperinsulinemia in DM type 2 activates the division and gifferentiation of osteoblasts and contributes to an increase in BMD. However, Higher BMD values in patients with DM type 2 are combined with slowdown in bone metabolism. As the result, high-quality bone remodeling does not occur. And bone strength decreases despite the high BMD. Despite the differences, DM type 1 and DM type 2 have common pathogenic pathways, that lead to increased bone fragility. For example, non-enzymatic glycation of bone matrix collagen and increase in concentration of sclerostin, which blocks the Wnt signaling pathway. In this review, we will analyze current data about epidemiology and pathogenesis of osteoporosis in DM and discuss the practical issues of the clinic, diagnosis, stratification of fracture risk and treatment. Special attention will be paid to the effects of glucose-lowering and anti-osteoporotic drugs on bone tissue.

Bioactivation of Bovine Bone Matrix and Collagen Scaffold Using Argon Plasma: In Vitro Study.

Bone graft materials and soft tissue allografts are widely used in clinical practice to counteract physiologic postextraction site tridimensional shrinkage. The aim of this study was to test if plasma of argon treatment could have a bioactivation effect on hard and soft tissue scaffolds in clinical usage. Forty-eight bovine bone matrix and porcine collagen samples were subdivided into two groups (test and control) of 12 samples each. The test group was treated with argon plasma (10 W, 1 bar for 12 minutes), while the control group was left untreated. Immediate cell adhesion and a proliferation assay at 72 hours were performed in the perfusion chamber of a bioreactor. Additionally, micro-CT analysis was performed on the treated and untreated scaffolds, before and after soaking in cell culture medium (four samples). Osteoblasts seeded on plasma-treated bone matrix significantly increased the adhesion level compared with the untreated sample (43,144.3 ± 12,442.9 vs 21,736 ± 77,27.1; P = .0083). However, 3-day proliferation tests could not achieve significant differences between groups (105,715.5 ± 21,751.5 vs 107,108.6 ± 19,343.4; P = .998). No differences were measured on fibroblast adhesion on the collagen matrix in both conditions. Plasma of argon treatment and soaking in cell culture medium did not affect the bone matrix samples. The structure of collagen matrix samples was unaltered after plasma treatment, but became enlarged after soaking. Plasma of argon may be useful to biofunctionalize bone grafts, although benefits seemed to disappear after 3 days. No biologic response was detected on collagen matrix scaffolds. In vivo studies are needed to draw final clinical conclusions.

Non-aqueous liquid crystals of hydroxyapatite nanorods

Hydroxyapatite (HA) nanorods in the collagen matrix of bone have a macroscopically ordered structure that has many similarities to the ordered structure of anisotropic nano-units in inorganic liquid crystals (LCs). Inspired by these similarities, we conducted the first (to our best knowledge) synthesis of HA LCs in non-polar solvents (such as cyclohexane and toluene), thus expanding the range of applicable monomers and polymers. We synthesized HA nanorods by a simple, effective, and oleic-acid-assisted hydrothermal route. The hydrothermal temperature directly modulates the aspect ratio of the HA nanorods, and indirectly modulates their LC behavior. The LC phase transition has no size limitation. Thus, our approach may be used to develop high solid content, macroscopically assembled, large-scale polymer-based bio(mimetic)-materials.

Decreased Bone Type I Collagen in the Early Stages of Chronic Obstructive Pulmonary Disease (COPD)

Smoking is the main risk factor for the development of chronic obstructive pulmonary disease (COPD) and is known to have deleterious effects on bone metabolism. However, the effects on bone collagen matrix during the development of COPD are unclear. The aim of this study was to evaluate the temporal effect of cigarette smoke exposure on bone type I collagen during COPD development in a cigarette smoke-induced model. C57BL/6 mice were allocated to three groups: control (C), animals exposed to filtered air for 1, 3 and 6 months; cigarette smoke (S), animals exposed to cigarette smoke for 1, 3 and 6 months; provisional smoking (PS), animals exposed to cigarette smoke for 3 months, followed by another 3 months of filtered air exposure. Evaluation of the respiratory mechanics and alveolar enlargement were performed. Femoral and tibial extraction was also performed to evaluate the type I collagen by immunofluorescence and COL1A1 gene expression. Exposure to cigarette smoke led to an alveolar enlargement and progressive reduction in lung tissue resistance and elastance, progressive reduction of type I collagen and reduction in COL1A1 gene expression. Although we did not observe any improvement in the functional and histological parameters in the provisional smoking group, we detected an increase in COL1A1 gene expression. A worsening in bone collagen matrix is part of the initial physiopathological events during COPD development and the smoking cessation induced an evident recovery of COL1A1 expression, possibly to attempt at tissue repair.