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Cellular and Molecular Determinants of Bone Formation

Cellular physiology of osteoblast during osseointegration Now we will discuss the cellular physiology associated with the process of osseointegration in detail Essential Concepts of Endosseous healing

1) Osteoblast is the prime bone matrix synthesizing cell. Like most secretory cells, osteoblasts are polarized cells, and the direction of their secretory activity is away from the nuclear end of the cell. The cell processes of osteoblasts become surrounded by mineralized matrix and, with their canaliculi, form the only means of vital communication between surface osteoblasts and those that have become completed surrounded by matrix as osteocytes. Thus the osteoblast is irrevocably attached to the bone-forming surface.

2) Osteoblasts have polarized synthetic activity. Thus bone can only be deposited by laying down matrix on a pre-existing solid surface i.e., bone only grows by apposition. Since each osteoblast may become a completely entombed osteocyte, the osteoblast is incapable of migrating away from the bone surface,and the only method by which this surface can receive further additions (beyond the synthetic capacity of a single osteoblast) is by the recruitment of more osteogenic cells to the surface, which then differentiate into secretory active osteoblasts.

3) Bone matrix mineralizes and has no inherent capacity to “grow.” This is quite different from other connective tissue, for example, cartilage, which can grow both interstitially and by apposition. Thus, once bone formation has been initiated, the matrix and the cells that have synthesized that matrix have almost no ability to govern the ongoing pattern of bone growth on the implant surface.

The osteoblast is the key for the development of new bone. It is essential that a large number of osteoblasts accumulate on the implant surface(contact osteogenesis).This process is called as Osteoblast recruitment. These cells are derived from the mesenchymal stem cells, the inner cell rich layer of the periosteum and the endosteum.Although systemic factors like hormones, ion concentration play a role in this process of recruitment, it is the local factors which are critical. It is signalling to precursor cells by the cytokines. Also bone morphogenic proteins which represent the osteoinductive proteins of bone are critical in this process of recruitment.After recruitment, the osteoblasts need to be attached to the implant surface. This is achieved by the extracellular matrix proteins which possess specific attachment sitesTherefore it is critical that the implant surface attract the attachment of these proteins derived from bone serum or surrounding matrix in order to attach the osteoblasts.

Some of these proteins include fibronectin, thrombospondin, osteopontin and osteoadherin (most of them have RGD cell binding peptide for binding; RGD refers to Arginine-Glycine- Aspartic Acid amino acid sequence) . After attachment the osteoblasts need to proliferate. The stimuli for this process include the cytokines and growth factors (platelet derived growth factor, insulin derived growth factors,Fibroblastic growth factors, transforming growth factor Beta) present around the cells and the hormones in circulation. Another factor that is important is the physicalor biomechanical strain.After proliferation the osteoblasts get differentiated into secretory osteoblasts which express collagen and extracellular matrix proteins and direct their mineralization.Collagen 1 and alkaline phosphatase are early markers of the differentiation process.
 
Bone sialoprotein is present prior to mineralization while osteocalcin is expressed along with mineralization. This process of differentiation and change of phenotype is regulated by hormones, growth factor and even mechanical strain.Molecular and cellular strategies to improve bone formation at implants.The healing response of biological tissues to the oxide surface is sensitive to the way in which the surface of the implant is made, cleaned and sterilized by the manufacturer.

A number of physical & chemical features of the oxide layer influence biological responses to the implants. These include the surface chemistry (oxide composition and thickness) surface energy, and surface topography (size, shape and roughness etc.) Experimental strategies to improve bone formation at implants are largely based on the ability of science to capture through gene cloning and recombinant protein technology, growth factors and extracellular matrix proteins that promote osteoblast recruitment, attachment, proliferation, and differentiation. These are used to dope or coat the implant surface. In addition, precise physicochemical alteration of implant surfaces can also improve cellular responses.The cellular basis for bone formation and maintenance of bone mass should be considered in any future synergistic combination of tissue engineering principles and biointegration of alloplastic materials.

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