Structure-mechanics relationships of collagen fibrils in the Osteogenesis Imperfecta Mouse model

The collagen molecule, which is the building block of collagen fibrils, is a triple helix of two α1(I) chains and one α2(I) chain. However, in the severe mouse model of osteogenesis imperfecta (OIM), deletion of the COL1A2 gene results in the substitution of the α2(I) chain by one α1(I) chain. As this substitution severely impairs the structure and mechanics of collagen-rich tissues at the tissue and organ level, the main aim of this study was to investigate how the structure and mechanics are altered in OIM collagen fibrils. Comparing results from atomic force microscopy imaging and cantilever-based nanoindentation on collagen fibrils from OIM and wild-type (WT) animals, we found a 33% lower indentation modulus in OIM when air-dried (bound water present) and an almost fivefold higher indentation modulus in OIM collagen fibrils when fully hydrated (bound and unbound water present) in phosphate-buffered saline solution (PBS) compared with WT collagen fibrils. These mechanical changes were accompanied by an impaired swelling upon hydration within PBS. Our experimental and atomistic simulation results show how the structure and mechanics are altered at the individual collagen fibril level as a result of collagen gene mutation in OIM. We envisage that the combination of experimental and modelling approaches could allow mechanical phenotyping at the collagen fibril level of virtually any alteration of collagen structure or chemistry.United States. Dept. of Defense. Presidential Early Career Award for Scientists and EngineersNational Science Foundation (U.S.) (CAREER Award

Relationships between density and Young’s modulus with microporosity and physico-chemical properties of Wistar rat cortical bone from growth to senescence

The aim of this study is to assess density and elastic properties of Wistar rat cortical bone from growth to senescence and to correlate them with morphological and physico-chemical properties of bone. During growth (from 1 to 9 months), bone density and Young’s modulus were found to increase from 1659±85 to 2083±13 kg m−3 and from 8±0.8 to 19.6±0.7 GPa respectively. Bone microporosity was found to decrease from 8.1±0.7% to 3.3±0.7%. Physico-chemical investigations exhibited a mineralization of bone matrix and a maturation of apatite crystals, as protein content decreased from 21.4±0.2% to 17.6±0.6% and apatite crystal size and carbonate content increased (c-axis length: from 151 to 173 Å and CO3W%: from 4.1±0.3% to 6.1±0.2%). At adult age, all properties stabilized. During senescence, a slow decrease of mechanical properties was first observed (from 12 to 18 months, ρ=2089±14 to 2042±30 kg m−3 and E3=19.8 ±1.3 to 14.8±1.5 GPa), followed by a stabilization. Physico-chemical properties stabilized while microporosity increased slightly (from 3.3% to 4%) but not significantly (p>0.05). A multiple regression analysis showed that morphological and physico-chemical properties had significant effects on density regression model. Microporosity had a greater effect on Young’s modulus regression model than physico-chemical properties. This study showed that bone structure, mineralization and apatite maturation should be considered to improve the understanding of bone mechanical behaviour

On “Understanding” in Wilhelm Dilthey

In the first part of this study, understanding and explanation will be considered from Dilthey’s distinction between natural sciences and human sciences. The second part, which sets forth the meaning and importance of life-expressions that enables understanding, is on elementary understanding and its background. As for the third and the last part, it approaches the higher understanding and hermeneutics in Dilthey which emerge from the insufficiency of elementary understanding

Nano-Engineered Scaffold for Osteoarticular Regenerative Medicine

In the last decade, regenerative medicine has benefited from the exponential development of nanomaterial sciences, tissue engineering and cell-based therapies. More and more sophisticated designed structures and surface topologies are being developed to basically mimic the extracellular matrix of native tissues such as cartilage and bone. Here we give an overview of the progress made in osteochondral lesion repair, with nano-engineered scaffolds comprising building blocks such as nanoparticles, nanotubes, layer-by-layer nano-assemblies, molecular self-assembly, nanopatterned surfaces…. This nano-engineering technology is coupled with bio-functionalization, by the use of adhesion peptides, growth factors, or deoxyribonucleic acid, to drive cell adhesion, proliferation and behavior towards tissue regeneration. In osteochondral regeneration, the challenge is the simultaneous development of chondrocytes and cartilage extracellular matrix on the one side and a well vascularized bone tissue with osteoblasts on the other sid

Increased autophagy in EphrinB2-deficient osteocytes is associated with elevated secondary mineralization and brittle bone

Mineralized bone forms when collagen-containing osteoid accrues mineral crystals. This is initiated rapidly (primary mineralization), and continues slowly (secondary mineralization) until bone is remodeled. The interconnected osteocyte network within the bone matrix differentiates from bone-forming osteoblasts; although osteoblast differentiation requires EphrinB2, osteocytes retain its expression. Here we report brittle bones in mice with osteocyte-targeted EphrinB2 deletion. This is not caused by low bone mass, but by defective bone material. While osteoid mineralization is initiated at normal rate, mineral accrual is accelerated, indicating that EphrinB2 in osteocytes limits mineral accumulation. No known regulators of mineralization are modified in the brittle cortical bone but a cluster of autophagy-associated genes are dysregulated. EphrinB2-deficient osteocytes displayed more autophagosomes in vivo and in vitro, and EphrinB2-Fc treatment suppresses autophagy in a RhoA-ROCK dependent manner. We conclude that secondary mineralization involves EphrinB2-RhoA-limited autophagy in osteocytes, and disruption leads to a bone fragility independent of bone mass