bone fracture and healing and tissue engineering of bone
BONE GROWTH AND FRACTURE HEALING AND TISSUE ENGINEERING OF BONE Introduction Perhaps if I had been given this essay title 20 years ago I would have had no problem with the ’bone fracture and healing’ part but would have been somewhat stuck on the tissue engineering aspect. As for the question ‘Is tissue engineering of bone possible?’ after a definition of tissue engineering had been given, then I probably would have dismissed it and put it in the sci-fi ‘pile’. Tissue engineering is such a new field that an official definition was given on 26 February 1988 in Lake Tahoe, CA. ... As a comparison, organ failure and tissue loss cost an estimated $400B in the United States alone. Tissue engineering is an emerging field linking biology and technology. Major science and popular science media such as Science, Nature, New Scientist and Scientific American have repeatedly featured tissue engineering as a field ready for revolutionary events that impact not only the postgenomic era in biology, but also health care delivery. Time magazine (May 22, 2000) predicted that tissue engineering would be “the Number One Hottest Job” in the next few decades. Many structures involved in health and diseases of the craniofacial region are bone and cartilage. ... population seek orthodontic treatment for correction of malocclusion; approximately 9 million Americans are totally edentulous and need sufficient craniofacial bone regeneration to support prosthesis for restoration of masticatory function; millions of Americans suffer from orofacial cancer and need bone regeneration for restoration of facial form. In short, bone and cartilage defects in the craniofacial region are not only a tremendous burden to society in terms of financial cost and time lost from work, but also a significant threat to the quality of life of virtually everyone. ... Add to this all other types of skeletal defects (traumatic and non-traumatic), and indeed all other organ systems defects, one can then truly begin to appreciate the potentials of Tissue Engineering. Bone and cartilage are widely believed to be the next tissues to be engineered in order to restore, maintain and improve their functions. Realizing the critical importance of bone and cartilage engineering multidisciplinary teams of scientists are working diligently to engineering bone and cartilage and attempt to apply some of the research findings in clinical situations where bone and cartilage are critically needed in patients. In collaboration with scientists elsewhere, a multitude of approaches from automated delivery of biomechanical stimuli, stem cells, cell labelling, PCR to atomic force microscope in attempts to promote maturation and regeneration of bone and cartilage are used. ... Tissue Engineering is being applied in every conceivable area where man is stricken with disease and trauma that lead to tissue loss. It is not surprising then why tissue engineering is recognised as a new major force in Biotechnology and one that is and will be changing the face of our lives for the better. Coupled with this is the fact that the average life span of population in industrialised countries is increasing (see tables 1 and 2), so one can only conclude that the need for tissue engineering can only increase. ... ANATOMY & PHYSIOLOGY OF BONE Introduction Bones are part of the skeletal organ system. ... The adult skeleton consists of 206 bones some of which are compact bone and the others spongy. ... Bone is hard, rigid and a highly specialised support tissue. ... (b) Short bones Usually cube shaped and spongy bone. ... A special type of short bone is called sesamoid (see (e) above). ... BONE STRUCTURE Tissues Bones contain several different types of tissues as such they are organs. The tissue contained in bone are: · Osseous or bone tissue · Nervous tissue · Cartilage tissue · Fibrous connective tissue · Muscle tissue · Epithelial tissue Gross Anatomy Every bone has a dense outer cortex and an inner trabecular region. ... The spongy zone is the inner trabecular region (also known as cancellous bone). The trabecular zone gives further strength to bone by a complex network of internal struts. The spaces between the trabecular meshwork house the bone marrow. Figure 3: (above left) Low-power SEM micrograph showing the architecture of bone (cortical and trabecular) and its relationship to the bone marrow. The cortical bone [C] is dense and forms a compact outer shell which is bridged by narrow, delicate plates of trabecular bone [T]. The spaces between the trabecular bone are occupied by yellow marrow (adipose tissue) or hemopoietic red marrow. Here the marrow [M] has retracted from the during tissue preparation. Figure 4: (above right) Medium-power SEM showing more detail of cortical and trabecular bone. ... In bones with a substantial weight-bearing function, the trabecular pattern is arranged to provide maximum resistance to the physical stresses to which the bone is subjected. Osteoid Osteoid refers to the specialized organic material found in the extracellular matrix of bone. It is a collagenous support tissue of type 1 collagen embedded in a glycosaminoglycan gel. ... The deposition of mineral salts in the osteoid gives bone rigidity and strength. TABLE 3: PROTEINS OF BONE MATRIX OSTEOBALST-DERIVED PROTEINS üType 1 collagen üCell adhesion proteins- osteopontin, fibronectin, thrombospondin üCalcium-binding proteins- osteonectin, bone sialoprotein üIvolved in mineralisation- osteocalcin ENZYMES üCollagenase üAlkaline phosphatase GROWTH FACTORS üInsulin-like Growth Factors- IGF-1, IGF-2 üPlatelet-Derived Growth Factor (PDGF) üacidic Fibrobalst Growth Factor- aFGF übasic Fibrobalst Growth Factor- bFGF üTransforming Growth Factors- TGF-Ò1, TGF-Ò2 üBone Morphogenic Proteins- BMP CYTOKINES üProstaglandins üIL1, IL-6 PROTEINS CONCENTRATED FROM SERUM üÒ2-microglobulin üAlbumin Getting the balance right Our clever bodies are master chefs, getting the ingredients to exact proportions to give the perfect recipe. ... If we just consider minerals and collagen, the correct proportions of each must be present in a good healthy bone. ... Figure 5: Typical normal bone is shown (top). Also shown is a demineralised bone, in which collagen is the primary remaining component (bottom left). ... In contrast, if collagen is removed leaving minerals as the remaining component then the bone is brittle and shatters easily (bottom right). STRUCTURE OF A TYPICAL LONG BONE Macroscopic view The Diaphysis or shaft is tubular and forms the long axis of a typical long bone. This is composed of a thick collar of compact bone surrounding a central marrow cavity. ... The Epiphyses are the bone ends. ... The core is made up of spongy bone surrounded by a layer of compact bone. Covering the surface is articular cartilage, which has the role of cushioning bone ends and absorbing stress. ... The epiphyseal line is a remnant of the epiphyseal plate, a disc of hyaline cartilage that grows during childhood to lengthen bone. When hormones stop the process of long bone growth at the end of puberty the cartilage is converted to bone leaving behind the distinct line. The periosteum is a double-layered connective tissue membrane covering the outer surface of bone except where there is articular cartilage. ... These reach the bone through the periosteum. The periosteum is the site of bone growth in diameter. The attachment mechanism to bone is made possible via tufts of collagen fibres known as Sharpey’s fibres. (See figure 6) Figure 6: Structure of a long bone (a) A typical long bone with longitudinal section through the proximal end exposing the yellow marrow in the shaft, and the gross spongy layout of the proximal epiphysis and part of the diaphysis. (b) 3D view of a spongy bone (c) section through diaphysis exposing yellow marrow, periosteum and sharpey’s fibers. Microscopic view Bone cells There are four main types of cells involved in the production and maintenance of bone: - 1) Osteoprogenitor cells- stem cells of bone that form osteoblasts 2) Osteoblasts- synthesize osteoid (the organic component of bone matrix) 3) Osteocytes- trapped in mineralized bone these are inactive osteoblasts 4) Osteoclasts- erode osteoid by enzymic hydrolysis Osteoprogenitor cells These are derived from primitive mesynchymal cells. They form a collective of stem cells that can differentiate into the more specialized bone-forming cells i. ... This is in mature bone where there is no active bone formation or remodeling, these cells become flattened and spindle like and are closely applied to the bone surface.