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Tesi etd-09232012-032901


Thesis type
Tesi di laurea specialistica LC6
Author
FREISLEDERER, FLORIAN
URN
etd-09232012-032901
Title
Nanostructured materials: a new approach to design orthopedic implants and innovative scaffolds for the treatment of bone and cartilage defects
Struttura
MEDICINA E CHIRURGIA
Corso di studi
MEDICINA E CHIRURGIA
Commissione
relatore Prof. Lisanti, Michele
Parole chiave
  • orthopedic implants
  • cartilage defects
  • bone defects
  • nanotechnology
Data inizio appello
16/10/2012;
Consultabilità
parziale
Data di rilascio
16/10/2052
Riassunto analitico
Due to the aging of the world’s population, the market for orthopedic implants is growing rapidly. Each year, over 600.000 joint replacements are performed in the USA alone, with an estimated worldwide cost in excess of 3 billion dollars. Today’s orthopedic implant materials do not allow patients to return to their normal, daily active lifestyles they enjoyed prior to the implant. As a result of these issues the average lifetime of orthopedic implants is only 10–15 years 2. Failed implants require several challenging revision surgeries, which drastically increase cost and recovery time. For young implant recipients especially, this means they will have to undergo several painful and expensive surgeries during their lifetime. For successful osseointegration, an orthopedic implant material must be inhabitable for bone-forming cells (osteoblasts), so that they can colonize on the implant surface and synthesize new bone tissue. Often implant materials are not compatible with these cells, but rather they promote the formation of soft connective tissue. There are a number of important reasons to explore the potential for use of nanomaterials in orthopaedic applications. As natural tissues are nanometer in dimension, and cells interact directly with, and create, nano-structured extra-cellular matrices (ECM), the biomimetic features and physiochemical properties of nanomaterials play a key role in both stimulating cell growth and guiding tissue regeneration. Natural tissues possess numerous nanometer features due to presence of collagen fibrils and other proteins less than 100 nm in one dimension. Bone tissue in particular possesses both proteins (such as collagen) and ceramics (hydroxyapatite and other calcium phosphates) that have fundamental dimensions less than 100 nm in at least one direction. When examining the surface roughness of bone, one can clearly see that it is a nanomaterial. Contrast this with the implants used today, which are smooth at the nanometer level and have average surface feature sizes closer to 10 to 100 microns. Nanometer or submicron surface structures have accelerated cellular responses by emulating the dimension, geometry, and arrangement of components of natural tissue. The range below 100 nm is crucial because the classic laws of physics change, resulting in novel physical properties that enable researchers to produce new materials with exact properties such as size and strength beyond conventional limits.<br>The use of nanotechnology has been tested on a wide range of materials (such as metals, ceramics, polymers, and composites), where either nanostructured surface features or constituent nanomaterials (including grains, fibers, or particles with at least one dimension from 1 to 100 nm) have been utilized. These nanomaterials have demonstrated superior properties compared with their conventional (or micron structured) counterparts, due to their distinctive nanoscale features and the novel physical properties that ensue. Nanomaterials have consistently been reported to decrease infection, reduce scar tissue growth, and promote bone growth. Interestingly, this has been observed through the use of both nanoparticles assembled as implants and as current implants that are modified to have nanostructured features. The latter have received increased attention, as there is no concern over nanoparticles becoming loose through mechanical wear and potential associated toxicity (which has yet to be largely determined). There are numerous examples of implants with nanorough surface features that mimic those that natural tissue possess, which have been shown to better promote tissue growth than do flat or nano-smooth (conventional) implants. A better design strategy may be to fabricate orthopedic implants (regardless of chemistry) to have structures similar to the nanoscale features of natural human bone. If so, this is a role for nanotechnology, or the use of nanophase materials, in orthopedic applications. In this context, modification of grain size, topography, pore, and/or particle size into the nanometer regime is simpler than developing novel chemistries which may or may not achieve improved osseointegrative properties. Another benefit is the significantly greater surface area that can be achieved through the use of nano-structured compared to micron-structured materials. To appreciate the surface area differential that can be achieved through the use of nanomaterials, immagine the difference between the surface area of a rock compared with the same volume of grains of sand. Surface area increases alone can be beneficial (if promoting bone growth) or detrimental (if promoting inflammation or infection). Therefore, it is the other properties related to greater surface area, such as higher surface roughness that allow nanomaterials to promote bone growth (8). More specifically, nanosized carbon tubes, nanoparticulate metals (such as Ti, CoCr, Ti6Al4V), nanoparticulate ceramics (hydroxyapatite (HA), titania, alumina, zinc oxide, etc.), and composite implant materials thereof have all been shown to increase tissue regeneration by promoting the adsorption and bioactivity of certain proteins, such as fibronectin and vitronectin, which are contained in plasma and are important for mediating tissue-forming cell adhesion. <br>Another topic I will focus on, is the use of nanostructured materials in tissue engineering for the healing of bone and cartilage defects. Extended bone defects, caused by trauma, tumor, infectious and periprosthetic osteolysis, need to be surgically treated because of their low potential of repair. Currently, bone allograft and autograft represent 80% of all transplantation done in the world. Withal, this technique shows many disadvantages, such as the risk of infections, the immunological rejection, the low bone availability and high costs. Minor cartilage defects, that do not involve the subchondral bone layer, won’t be repaired spontaneously. Where as major defects are healed intrinsically by a fibrocartilaginous repair tissue, much poorer than the original hyaline articular cartilage. The goal, however, is to produce a repair tissue that has the same functional and mechanical properties of hyaline articular cartilage. Since natural tissues or organs are nanometer in dimension and cells directly interact with (and create) nanostructured extra-cellular matrices (ECM), the biomimetic features and excellent physiochemical properties of nanomaterials play a key role in stimulating cell growth as well as guide tissue regeneration. By controlling surface properties, various nanophase ceramic, polymer, metal and composite scaffolds have been designed for bone/cartilage tissue engineering applications. The development of bioinspired nanocomposites has great potential to improve the efficacy of current orthopedic implants and tissue engineering constructs. For organic/inorganic biocomposites, it is possible to obtain a wide range of mechanical and biological properties by modifying the type and distribution of inorganic phase in the organic matrix, and hence to optimize the performance of the biomedical devices and their interaction with the host tissues. Current research is aswell exploring the potential use of mesenchymal stem cells as a source for tissue engineering and the combination of cells with biodegradable nanostructured scaffolds. The success of both the orthopedic implant and the tissue engineered construct is highly dependent on the interactions between the selected biomaterial and the host tissue. One of the key factors identified in the failure of both types of implants was insufficient tissue regeneration around the biomaterial immediately after implantation. This has been attributed to poor surface interaction of biomaterials with the host tissue. Materials with Nanostructured Surfaces have been shown to possess important skills to resolve the main concerns ortopedic surgery has to face.<br>
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