Advances in Biomimetics Part 11 pot

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Calcif Tissue Int 51(2):132-136. Ziambaras K, Lecanda F, Steinberg TH, Civitelli R (1998) Cyclic stretch enhances gap junctional communication between osteoblastic cells. J Bone Miner Res 13:218-228. 17 Novel Biomaterials with Parallel Aligned Pore Channels by Directed Ionotropic Gelation of Alginate: Mimicking the Anisotropic Structure of Bone Tissue Florian Despang 1 , Rosemarie Dittrich 2 and Michael Gelinsky 1 1 Max Bergmann Center of Biomaterials and Institute for Materials Science, Technische Universität Dresden, 01062 Dresden 2 Institut für Elektronik- und Sensormaterialien, TU Bergakademie Freiberg, 09596 Freiberg Germany 1. Introduction Regenerative medicine intends to restore lost functionality by healing tissues defects. For this novel types of biodegradable implants have to be used that first foster healing and later take part in the natural remodelling cycle of the body. In this way, patient’s cells can reconstruct and adapt the tissue according to the local situation and needs. Ideally, the implant should mimic the desired tissue. That means that the biomaterial should resemble the extracellular matrix (ECM) which is expressed by specific cells and acts as the biological scaffold of living tissues. The closer an artificial scaffold material mimics the pattern the easier it can be involved in the natural healing and remodelling processes, which is why more and more researchers try to establish biomimetic approaches for the development of tissue engineering scaffolds. Biological materials are seldom isotropic and for many tissue engineering applications distinct anisotropic materials are needed. E. g. compact bone exhibits a honeycomb-like structure with overlapping, cylindrical units (osteons) with the so-called Haversian canal in the centre. Scaffolds with parallel aligned pores, mimicking the osteon structure of compact bone can be synthesised by directed ionotropic gelation of the naturally occurring polysaccharide alginate. The parallel channels are formed via a sol-gel-process when di- or multivalent cations diffuse into the sol in broad front, forming an alginate hydrogel. The pore size and pore alignment of such gels is influenced by the starting materials (e.g. concentrations, additives like powders or polymers) and the preparation process (e.g. temperature, drying process). The phenomenon was discovered already in the 50 th of the last century but the biomedical potential of alginate scaffolds with parallel aligned pores structured by ionotropic gelation has been explored for osteoblasts, stem cell based tissue engineering, axon guiding or co-culture of vascular and muscle cells only in the past few years. 2. Biomimetic approaches for biomaterials and Tissue Engineering (TE) In natural tissues, cells are embedded in three dimensional, fibrous environments – the so called extracellular matrix (ECM). General task of the ECM is to act as a scaffold for cell Advances in Biomimetics 350 adhesion, to provide certain mechanical stability and elasticity, to protect the cells and to facilitate the development of the proper cell morphology. In addition, ECM is the space of nutrient and oxygen supply, of intercellular communication and it is relevant for storage of water and soluble substances. Each ECM is perfectly adapted to the special needs of a distinct tissue and its dedicated cells. When developing artificial tissues in terms of tissue engineering a biomaterial called scaffold has to take over the basic functions of the natural ECM, at least until the construct has been fully integrated and remodelled by the host tissue after implantation. It is obvious that it is difficult to design artificial materials which meet all the requirements described above. Therefore many researchers started to mimic the natural ECM with their scaffold material, either concerning chemical composition, micro- or nanostructure or special properties like anisotropy which is also an important feature of most tissues (Ma, 2008). Biomimetic strategies can include the utilisation of ECM components like natural biopolymers (e. g. collagen), material synthesis under physiological conditions (37°C, pH of 7.4, buffered aqueous solutions etc.) or the creation of structural features similar to those of extracellular matrices. The better an artificial scaffold material mimics its biological model, the faster it will be integrated by the host tissue after implantation and the easier it will be included in the remodelling cycle, leading finally to a complete degradation and healing of the defect. 3. Bone tissue: a natural, highly anisotropic nanocomposite material In humans (general in mammals), different types of bone exist or are formed intermediately during development or healing, mainly cortical (compact), spongy (trabecular) and woven bone (Weiner & Wagner, 1998). Their organisation is highly hierarchical, but at the lowest level all consist of the same nanocomposite, made of fibrillar collagen type I and the calcium phosphate phase hydroxyapatite (HAP). Collagen is produced by bone cells called osteoblasts, which also express the enzyme alkaline phosphatise (ALP), necessary for calcium phosphate mineral formation. A variety of non-collagenous proteins, also synthesised by osteoblasts, are responsible for control of the matrix formation and mineralisation processes, but the molecular mechanisms are not completely understood yet. With the exception of woven bone, collagen fibrils are deposited in an alternating, sheet-like manner and with a parallel fibre alignment (called “lamellae”) into the free space, created by resorbing osteoclasts during bone remodelling. Lamellae form osteons in compact bone – always aligned parallel to the bone axis – and trabecules in spongy bone (Rho et al., 1998). These structure elements are responsible for the outstanding mechanical properties of bone tissue and its perfect adaptation to the local force distribution. Compact bone has only pores with diameters in the micrometer range, filled either with blood capillaries (Haversian canals, located in the centre of the osteons) or osteocytes (lacunae – interconnected by the canaliculi pore system). In contrast, the trabecules in spongy bone form a highly open porous structure with pore widths of up to a few millimetres. Fig. 1 shows the hierarchical organisation of (cortical) bone tissue – from the macroscopic organ down to the nanometre scale. 4. Directed ionotropic gelation of alginate – a biomimetic method for generating anisotropic materials Alginate is the structural saccharid of brown algae. Being a co-polymer, it consists of mannuronic (M) and guluronic acid (G) monosaccharide units, possessing identical [...]... cross-linked, Cu-gelled alginate hydrogels with in vitro (entorhinal-hippocampal slice culture) & in vivo (spinal cord) experiments in rats Axonal regrowth on Cu2+-, Ni2+- or Ba2+-alginate hydrogels (after ion exchange) with in vitro & in vivo experiments in rats Al2O3 membrans based on Cu2+- or Ca2+-alginate-slurries including optimized drying procedure, consolidation and permeability data Influence... gradient in the direction of the long axis of the pore channels can be obtained by carefully covering layers of alginate sol on top of each other which differ in composition (Gelinsky et al., 2007) Bi-phasic but monolithic scaffolds consisting of a hydrogel -part and a 362 Advances in Biomimetics mineralised part were under current investigations for regeneration of osteochondral defect Both parts contain... Pompe, W & Gelinsky, M (2006) Mineralized Scaffolds for hard tissue engineering by ionotropic gelation of alginate, In: Vincenzini, P (ed.) Advances in Science and Technology, Vol 49, 159-164, trans tech publications inc Dittrich, R.; Despang, F.; Bernhardt, A.; Hanke, Th.; Tomandl, G.; Pompe, W & Gelinsky, M (2007) Scaffolds for hard tissue engineering by ionotropic gelation of alginate influence of... interpretation of change of electrolyte concentration: influence of ionic radius and electrolyte density; model of intra- and intermolecular binding of cations to alginate chains Modelling of the integration of alginate chains to the growing gel by conformational changes/degree of contraction (length of chain, velocity of gelation front, velocity of cross-linking reaction) Summary of new theory on capillary... (alternating calcium and phosphate ions) in broad front into the hydrogel in some runs creating initially brushit which can be transformed into HAP (Thiele & Awad, 1969), 360 • • • Advances in Biomimetics Synchronous mineralisation, i.e precipitation of calcium phosphate during the sol-gelprocess (Despang et al., 2005), HAP powder, i.e addition of HAP powder to the alginate sol and structuring of this... consolidation started by sintering Nano-sized pores of the walls were filled during sintering but the macro-porosity as relevant parameter for cell ingrowth remained unaffected Face surface Longitudinal section Fig 8 Osteogenically induced hMSC after 14 days of in vitro cultivation on nano-crystalline HAP scaffolds in the state as brown body (Ca2+ gelled slurry) – SEM (200x) after supercritical drying Fig 9 Hydroxyapatite... Gelation of Alginate: Mimicking the Anisotropic Structure of Bone Tissue 367 due to the small particle size Further heating to sintering temperatures of 1200°C leads to stable ceramics with higher mechanical strength But during the sintering step, the HAP grains grow, making the product hardly degradable for osteoclasts (and therefore in vivo) Fig 13 gives an overview about the four main types of materials... [German] Thiele, 1967 [German] Advances in Biomimetics Content Alignment and gelation of anisometric particles in colloidal solutions (thin layer), resulting in birefringence pattern in polarized light First full article on alignment and gelation of anisometric particles in colloidal solutions, but not yet about capillary formation Dependence of alignment of anisometric particles on type and concentration... strategies in biomimetic material design and manufacturing involve the generation of hierarchical assemblies of multiple components; therefore the bioactive and self healing products that are thus obtained get referred to as “functional hybrids” Although these 374 Advances in Biomimetics products are useful in diverse fields, such as the auto industry, computer logics and the wine industry, their main application... processing for membrane manufacturing was studied with Al2O3 or TiO2 including development of adapted drying regimes for the wet composites applying method inherent shrinkage, followed by heat treatment to obtain a sintered ceramic without cracks (Weber et al., 1997; Dittrich et al., 2002; Eljaouhari et al., 2006) Dittrich et al (2002) for the first time synthesised such ceramics consisting of the mineral . obstruction in children. Laryngoscope 111 (7) :113 7 -114 6. Advances in Biomimetics 348 Sorkin AM, Dee KC, Knothe Tate ML (2004) “Culture shock” from the bone cell’s perspective: emulating physiological. density; model of intra- and intermolecular binding of cations to alginate chains Woelki & Kohler, 2003 Modelling of the integration of alginate chains to the growing gel by conformational. (alternating calcium and phosphate ions) in broad front into the hydrogel in some runs creating initially brushit which can be transformed into HAP (Thiele & Awad, 1969), Advances in Biomimetics