Order versus Disorder: in vivo bone formation within osteoconductive scaffolds

In modern biomaterial design the generation of an environment mimicking some of the extracellular matrix features is envisaged to support molecular cross-talk between cells and scaffolds during tissue formation/remodeling. In bone substitutes chemical biomimesis has been particularly exploited; conversely, the relevance of pre-determined scaffold architecture for regenerated bone outputs is still unclear. Thus we aimed to demonstrate that a different organization of collagen fibers within newly formed bone under unloading conditions can be generated by differently architectured scaffolds. An ordered and confined geometry of hydroxyapatite foams concentrated collagen fibers within the pores, and triggered their self-assembly in a cholesteric-banded pattern, resulting in compact lamellar bone. Conversely, when progenitor cells were loaded onto nanofibrous collagen-based sponges, new collagen fibers were distributed in a nematic phase, resulting mostly in woven isotropic bone. Thus specific biomaterial design relevantly contributes to properly drive collagen fibers assembly to target bone regeneration

Liquid crystalline properties of type I collagen: Perspectives in tissue morphogenesis

Collagen molecules form the major part of tissues like bone, cornea or tendon where they organize into ordered fibrillar networks. The acid-soluble protein spontaneously assembles in liquid crystalline phases, characterized in polarized light microscopy and X-ray diffraction. Collagen fibrillogenesis obtained in condensed media establishes a link between the fibrillar networks described in vivo and the mesomorphic states obtained in vitro. Cellematrix interactions on these biomimetic materials are currently analysed with perspectives in tissue engineering. In a morphogenetic context, we propose the hypothesis of a liquid crystalline order, between soluble precursor molecules, preceding fibrillogenesis

Water-mediated structuring of bone apatite

International audienceIt is well known that organic molecules from the vertebrate extracellular matrix of calcifying tissues are essential in structuring the apatite mineral. Here, we show that water also plays a structuring role. By using solid-state nuclear magnetic resonance, wide-angle X-ray scattering and cryogenic transmission electron microscopy to characterize the structure and organization of crystalline and biomimetic apatite nanoparticles as well as intact bone samples, we demonstrate that water orients apatite crystals through an amorphous calcium phosphate-like layer that coats the crystalline core of bone apatite. This disordered layer is reminiscent of those found around the crystalline core of calcified biominerals in various natural composite materials in vivo. This work provides an extended local model of bone biomineralization

Triple-helical collagen hydrogels via covalent aromatic functionalization with 1,3 phenylenediacetic acid

Chemical crosslinking of collagen is a general strategy to reproduce macroscale tissue properties in physiological environment. However, simultaneous control of protein conformation, material properties and biofunctionality is highly challenging with current synthetic strategies. Consequently, the potentially-diverse clinical applications of collagen-based biomaterials cannot be fully realised. In order to establish defined biomacromolecular systems for mineralised tissue applications, type I collagen was functionalised with 1,3-phenylenediacetic acid (Ph) and investigated at the molecular, macroscopic and functional levels. Preserved triple helix conformation was observed in obtained covalent networks via ATR-FTIR (AIII/A1450 [similar] 1) and WAXS, while network crosslinking degree (C: 87–99 mol%) could be adjusted based on specific reaction conditions. Decreased swelling ratio (SR: 823–1285 wt%) and increased thermo-mechanical (Td: 80–88 °C; E: 28–35 kPa; σmax: 6–8 kPa; εb: 53–58%) properties were observed compared to state-of-the-art carbodiimide (EDC)-crosslinked collagen controls, likely related to the intermolecular covalent incorporation of the aromatic segment. Ph-crosslinked hydrogels displayed nearly intact material integrity and only a slight mass decrease (MR: 5–11 wt%) following 1 week incubation in either PBS or simulated body fluid (SBF), in contrast to EDC-crosslinked collagen (MR: 33–58 wt%). Furthermore, FTIR, SEM and EDS revealed deposition of a calcium–phosphate phase on SBF-retrieved samples, whereby an increased calcium phosphate ratio (Ca/P: 0.84–1.41) was observed in hydrogels with higher Ph content. 72 hours material extracts were well tolerated by L929 mouse fibroblasts, whereby cell confluence and metabolic activity (MTS assay) were comparable to those of cells cultured in cell culture medium (positive control). In light of their controlled structure–function properties, these biocompatible collagen hydrogels represent attractive material systems for potential mineralised tissue applications