Giugliano, Daniela (2014) MULTICOMPONENT BIOMIMETIC SYSTEMS FOR BONE AND OSTEOCHONDRAL DEFECTS. [Tesi di dottorato]

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Abstract

The extracellular matrix of bone has been described as a composite material made constituted by collagen type I fibrils mineralized with nanocrystals of hydroxyapatite. Approximately 70% of bone by weight is composed of calcium salts, with hydroxyapatite Ca10(PO4)6(OH)2 as the primary mineral constituent. Bone formation occurs in two phases: matrix synthesis followed by extracellular mineralization. An impaired balance of bone resorption and formation by osteoclasts and osteoblasts, respectively, induces osteoporosis. Other bone defects can be caused by tumor removal, fractures (especially in the hip, wrist, knee and spine) or congenital defects. A more complex substrate is represented by osteochondral tissue, where defects penetrate the subchondral bone. To mimic natural structure, we propose different approaches to repair bone and osteochondral defects and to promote a potential bone healing filler. In general, injectable materials (cements/natural polymer) hold great promise in tissue engineering applications due to the ability of these systems to conform to complex bone shapes, contours, and defects with less invasive surgery. The target is the osteogenic differentiation induced by bioactive component (natural polymers and/or modified hydroxyapatite) of the injectable systems. In this work, we proposed the following bone filler materials: 1. Strontium-substituted hydroxyapatite cement (to contrast bone resorpsion). 2. Bioactive hydroxyapatite - graphene oxide (to support high viability and osteogenic differentiation of hMSC cells). 3. Modified-cellulose hydrogels crosslinked by citric acid (to increase hydrophilicity and roughness surface in order to stimulate osteogenic differentiation of hMSC). Osteocondral region has two distinct tissues (bone and cartilage) with different properties: to mimic its structure, we realized two different gelatin scaffolds biomineralized by HA. The use of a 3D scaffold depends on the necessity to provide a shape control, while the biological signals are induced by HA presence, realized by bulk sol-gel transition, and surface biomimetic treatment, as reported in the two type of scaffolds realized: 1. Gelatin scaffold crosslinked by EDC solution, and biomineralized by modified Kokubo treatment (to increase osteogenic proliferation and differentiation); 2. Gelatin/hydroxyapatite scaffold realized by in situ sol-gel synthesis and crosslinked by EDC solution (where the biological signals occur into the scaffold as a gradient and crystalline degree is modulated by gelatin/hydroxyapatite ratio).

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