Page 137 - Physico-Chemical Niche Conditions for Bone Cells

INTRODUCTION
Biomaterials are used to replace bone in pathological conditions such as tooth loss, osteoarthritis, or large bone defects as a result of trauma or tumor removal [1]. In the case of tooth loss or osteoarthritis, the tooth or joint is replaced by a prosthesis, which has to integrate into the native bone. When large bone defects are concerned, resorbable grafts are inserted which in time are replaced by native bone. The integration of both implants and bone grafts starts with cell recruitment, adhesion, proliferation, and differentiation [1–3]. Implant integration requires that osteoprogenitors and mesenchymal stem cells are recruited, attach to the implant, proliferate, and differentiate into bone forming osteoblasts [2,3]. To allow bone graft integration, osteoclast precursors that differentiate and fuse to become bone graft resorbing osteoclasts are also needed [1]. The most important challenge in bone tissue engineering is the development of biomaterials that promote adhesion, proliferation, and differentiation of osteoprogenitors and osteoclast precursors, while repelling adhesion of bacteria, that may cause infection, and cells that produce a membranous structure between the biomaterial and the bone leading to implant failure [2,3]. For improved bone regeneration and seamless biomaterial integration into the bone, innovative biomimetic coatings for biomaterials are still needed.
Adhesion, proliferation, and differentiation of osteoprogenitors are affected by integrin binding and focal adhesion formation. Cells adhere to extracellular matrix (ECM) primarily by the binding of integrin receptors to proteins within the ECM [4]. Integrin binding induces the formation of adhesion complexes where integrins cluster together, and where scaffolding and signaling proteins are recruited and attach to the actin cytoskeleton [4–6]. Focal adhesions strengthen osteogenic cell attachment to the ECM and induce cell spreading and morphology changes by remodeling the actin cytoskeleton [7,8]. The signaling resulting from focal adhesion formation regulates the activity of transcription factors that direct cell growth, proliferation, survival, and differentiation toward osteoblasts [4,6,8].
Several approaches have been employed to improve the adherence and differentiation of cells on biomaterials. Improved osseointegration is observed when using implants with a rough surface compared to a smooth surface [2,9]. Surface chemistry also influences cellular adhesion [10]. Cell adhesion and differentiation on biomaterials can also be improved by anchoring small peptides to the biomaterial surface. One of these peptides is arginine-glycine- aspartate (RGD), a ligand for integrins found in ECM components such as fibronectin, vitronectin, osteopontin, and bone sialoprotein [11]. RGD has been immobilized to different substrates, including liquid crystals [12], titanium alloys [7,13,14], and amine functional self- assembled monolayers [15]. RGD has been shown to either have no effect on osteoprogenitor adhesion [12,14] or to positively affect osteoprogenitor adhesion [7,13,15] and differentiation
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