Sharma Biointegration of Medical Implant Materials

Science and Design
1. Auflage 2010
ISBN: 978-1-84569-980-2
Verlag: Elsevier Science & Techn.
Format: EPUB
Kopierschutz: 6 - ePub Watermark

E-Book, Englisch, 424 Seiten

Reihe: Woodhead Publishing Series in Biomaterials

Biointegration is essential for the successful performance of implanted materials and devices within the human body. With an increasing number and wide range of implant procedures being performed, it is critical that materials scientists and engineers effectively design implant materials which will create a positive biological and mechanical response with the host tissue.Biointegration of medical implant materials provides a unique and comprehensive review of recent techniques and research into material and tissue interaction and integration. Part one discusses soft tissue biointegration with chapters on the biocompatibility of engineered stem cells, corneal tissue engineering and vascular grafts. Part two then reviews particular techniques in drug delivery including inorganic nanoparticles for targeted drug delivery and alginate based drug delivery devices. Part three covers design considerations with coverage of themes such as biocompatibility of materials and its relevance to drug delivery and tissue engineering, mechanisms of failure of medical implants during long term use and rapid prototyping in biomedical engineering.With its distinguished editor and team of international contributors, Biointegration of medical implant materials: science and design is a standard reference for medical materials scientists and engineers in industry and the academic sector. - Provides a unique and comprehensive review of recent techniques and research into material and tissue interaction and integration - Discusses soft tissue biointegration with chapters on the biocompatibility of engineered stem cells, corneal tissue engineering, vascular grafts and replacement materials for facial reconstruction - Reviews particular techniques in drug delivery featuring inorganic nanoparticles and functionalized nanoparticles for targeted drug delivery

Autoren/Hrsg.

Sharma, Chandra P.

Leseproben

2 Biocompatibility of engineered soft tissue created by stem cells
P.A. Clark,     University of Wisconsin–Madison, USA J.J. Mao,     Columbia University, USA Abstract:
Orthopedic and dental implants replace millions of arthritic, traumatic or lost skeletal or dental structures. All orthopedic or dental implants can fail, and the central reason for failure is that metallic implants do not remodel with host tissue. Current implants rely primarily on tissue growth onto implants or an ‘outside-in’ strategy. This chapter discusses an ‘inside-out’ strategy to induce tissue ingrowth by cytokine delivery. Drug-eluting porous implants have the advantage not only of reducing bulk metal mass, but also of harboring cytokines that are programmed to release into surrounding tissue. This coupled inside-out and outside-in strategy improves bone ingrowth. Key words orthopedic implants medical implants cardiac implants dental implants growth factors cytokines controlled release microencapsulation 2.1 Introduction
Tissue and organ defects resulting from trauma, chronic diseases, tumor resection or congenital anomalies necessitate the restoration of the lost anatomical structures. Due to a lack of biological replacements for skeletal structures, implantation of biocompatible metals such as titanium is currently the preferred treatment (Ratner et al., 1996; Misch, 1993; Kienapfel et al., 1999). Despite high success rates of initial anchorage (over 90%) (Ashley et al., 2003), titanium implants require long healing times before functional loading, and are subject to failure from inadequate initial bone ingrowth or long-term osteolysis at the bone–implant interface. Current approaches in modifying titanium implants to overcome these limitations focus on biomaterial composition and processing, surface roughening, and chemical surface modification, among others. Taking cues from biology and tissue engineering has led to the idea of biointegration, entailing the use of biologically active agents to modulate the bone ingrowth process and improve implant anchorage. Biointegration of orthopedic implants represents a daunting task considering the complex environment of healing and homeostatic bone, but fortunately the fields of tissue engineering and drug delivery have developed micron- and nano-scale systems for controlled release of various biologically active agents. This chapter will first address the key biological considerations of biointegration of orthopedic implants. Mimicking these processes using drug delivery systems toward improved short- and long-term efficacy in these implants will then be discussed, concluding with future trends in this emerging field. 2.2 Bone: from tissue to molecular organization
Bone is the main weight-bearing tissue of the body, with varying and complex macroscopic designs due to its distinct functions in different regions of the body. In general, bone exists either as cortical with low porosity and high density, or cancellous (or trabecular) with microscopic interconnecting bony trabecula giving macroscopically high porosity and low density (Marks and Odgren, 2002). Biochemically, bone is composed of about 35% organic matrix (osteoid), mainly Type I collagen fibers along with proteoglycans and noncollagenous proteins, and about 65% inorganic mineral, mainly calcium and phosphate in the form of hydroxyapatite (Lind, 1998; Misch, 1993). This general composition gives bone marked rigidity while retaining some elasticity (Marks and Odgren, 2002), with the collagen fibers of the organic matrix providing high tensile strength to resist pulling forces and the inorganic mineral providing high compressive strength to resist crushing forces (Marks and Odgren, 2002; Misch, 1993; Alberts et al., 2002). A key facet of bone tissue during development and maintenance is the constant re-organization of the extracellular matrix to satisfy local load-bearing requirements. This process is driven by the two main cell pheno-types of bone: bone-forming osteoblasts and bone-resorbing osteoclasts (Marks and Odgren, 2002; Hole and Koos, 1994). Acting as possible sensors and signaling agents for the osteoblasts and osteoclasts are the osteocytes, post-mitotic terminally differentiated osteoblasts encased in bone matrix that communicate via long processes known as canaliculi (Marks and Odgren, 2002). Located in the cavities of long bones and among trabecula in cancellous bone is the bone marrow. This tissue contains both red marrow, the site of new blood cell production or hematopoiesis throughout life, and yellow marrow, which is mostly fat cells (Hole and Koos, 1994). The bone marrow generally transitions from red to yellow with age, although this trend can be reversed in injurious or other special instances (Hole and Koos, 1994). The marrow contains a milieu of cells, including red and white blood cells, osteoblasts, fibroblasts, adipocytes (fat cells), and blood vessel cells (Hole and Koos, 1994). Fibroblast-like cells residing within the bone marrow stroma, or connective tissue of the marrow, have also been isolated that possess extensive proliferative potential and differentiation ability to multiple mesenchymal lineages, including osteoblasts, chondrocytes (cartilage cells), and adipocytes (Pittenger et al., 1999; Caplan, 1991a,b; Alhadlaq and Mao, 2004; Cassiede et al., 1996). These multipotential cells, termed mesenchymal stem cells (MSCs) or bone marrow stromal cells, likely play a key role in repair after injury, and are present throughout life (Caplan, 1991b; Alhadlaq and Mao, 2004). Lining the outer wall of the marrow cavity and the outer surface of bones are thin linings of tissue called the endosteum and periosteum, respectively. These tissues are similar in composition and morphology, being composed of flattened cells (Marks and Odgren, 2002). Recently, the endosteal lining has been identified as an important hematopoietic stem cell (HSC) ‘niche’, the specialized compartment in which stem cells reside (Scadden, 2006; Taichman, 2005). Through strict control of the microenvironment, the endosteal cells maintain the HSCs, which can differentiate to every blood lineage, until they are needed (Taichman, 2005; Scadden, 2006). The endosteum and periosteum may also contain osteoprogenitor cells that can mobilize after injury (Hutmacher and Sittinger, 2003; Hanada et al., 2001). Not to be forgotten, like any tissue, bone and its marrow require a rich vascular supply for oxygen and nutrients and for disposal of waste products. As will be discussed later in the chapter, vessel formation or ingrowth is critical for bone formation during development and after injury. Mural cells associated with blood vessels, particularly the pericytes, have demonstrated multilineage potential and may also participate in bone repair after injury (Collett and Canfield, 2005; Doherty and Canfield, 1999). The tissue and cellular processes that organize and maintain bone are molecularly coordinated and controlled largely by bioactive chemicals termed cytokines or growth factors (Gilbert, 1997). During development, homeostasis, and after injury, a multitude of skeletal growth factors act as both temporal and spatial coordinating molecules to induce chemotaxis, mitosis, differentiation, changes in extracellular matrix production, and even apoptosis (Roberts, 2000; Alliston and Derynck, 2000). These cytokines can exert their effects on local cells (paracrine), on the same cells that released them (autocrine), or after absorption and transport via the blood-stream (endocrine) (Lind, 1998). Some cytokines exert their effects on very specific lineages of cells while others exhibit context-dependent effects on multiple cell phenotypes. Growth factor effects on cells depend heavily on the dosage, with most cells demonstrating biphasic responses. Some of the most well-studied cytokines in skeletal biology are members of the transforming growth factor ß (TGFß) superfamily, which include multiple TGFß isoforms and the bone morphogenetic proteins (BMPs). Members of this superfamily play important and oftentimes critical roles in the growth and maintenance of bone and cartilage. Perhaps most strikingly, the BMPs were discovered by Marshall Urist in 1965 by their ability to induce ectopic bone formation in skeletal muscle (Lou, 2001; Linkhart et al., 1996; Lind, 1998; Urist, 1965; Urist et al., 1979). Fibroblast growth factors (FGFs) and the insulin-like growth factors (IGFs) also participate in many skeletal development and repair processes (Marie et al., 2002; Linkhart et al., 1996). Important to vasculogenic and angiogenic processes, and therefore to bone development and homeostasis, are vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF) (Lind, 1998; Franceschi, 2005; Gerstenfeld et al., 2003). Details of these, as well as other...