Biomedical Engineering Reference
In-Depth Information
to the bone graft substitute materials is the surface morphology. Considering the cell size
(µm) and the interface (EDL) thickness (nm), it should be the surface morphology which
certainly maintains comfortable hosting for the cell to adhere, to fine tune their micro
environment, and to communicate with other cells. The main parameters to consider are
particles size, shape, porosity, surface (macro and micro) roughness, and availability of
natural and artificial scaffolds. Initial morphology is not kept during the formation of new
bone; however it can contribute at the first stage of the tissue regeneration process.
“Biomaterial in biological media” system can be separated to three different parts: solid
phase (macro), solution phase (macro), and solid-solution interface (nano). Continuous
phases are easy to investigate, but the most important information about the interface is
almost inaccessible. The formation of new bone can be experimentally observed already at
micro level using histological sections of biopsies from patients; changes in composition of
biological media are routinely monitoring by standard chemical tools. However, specific
characteristics necessary for a potential interfacial “nano-reactor” and the key elements
which initiate and control cellular activity are still unknown. To understand these
phenomena at a molecular level we need supplementary physico-chemical information
about the surface of bone graft substitute material and the immediate interface between the
material and the biological media. This information will allow material scientists and bone
biologists to improve existing or to create a new tissue substitutes with attractive interface
properties, leading the cell towards the decision - “To build or not to build” the bone.
2. Biomaterials and bone cell interactions
Although bone is unique in terms of being able to repair itself (e.g. fracture healing), bone
defects caused by trauma and pathological conditions will not always heal spontaneously
(Feng & McDonald, 2011; Nakahama, 2010). Autologous bone graft is considered the best
treatment option, but has the limitation of donor sites, and the interest for bone graft
substitute materials is increasing (Porter et al., 2009). Ideally, bone formation induced by the
biomaterial will mimic the physiological process where osteoblasts differentiate from
mesenchymal stem cells and produce extracellular proteins that serve as a template for the
biomineralization process. It is crucial that the biomaterial does not promote an imbalanced
bone remodeling process with uncoordinated activities between bone forming osteoblasts
and bone resorbing osteoclasts. Osteoclasts are multinucleated cells with a hematopoietic
origin formed by fusion of mono nuclear cells mainly regulated by osteoblasts and stromal
cells (Raggatt & Partridge, 2010).
Cell differentiation in general is regulated by complex interacting signaling pathways which
eventually lead to altered gene expression and subsequent changes in cell behavior. The
interaction between cell surface molecules and extracellular structures is one of the key
mechanisms regulating the differentiation and activities of bone cells. Mesenchymal stem
cells and stromal cells, including osteoblasts, as well as osteoclasts, are depending on
attachment to extra cellular matrix (ECM) proteins. Cellular interactions with adhesion
proteins/ECM proteins occur via transmembrane integrins receptors which recognize
proteins containing the Arg-Gly-Asp (RGD) amino acid sequence. The RGD sequence can be
found within proteins such as fibronectin and vitronectin which are components in ECM
and interestingly also among the serum proteins which are adsorbed to implanted surfaces
(Kundu & Putnam, 2006; Raggatt & Partridge, 2010; Wilson et al., 2005). Vitronectin is
reported to promote osteogenic differentiation of mesenchymal stem cells via integrin-
