6 In the next step, soft callus is gradually removed and replaced by mineralized bone matrix. The newly enough formed woven bone is called hard callus, is typically irregular, and needs to be remodeled.7 This repair stage represents the most active period of osteogenesis with high levels of osteoblast activity. In the remodeling phase the woven bone is transformed into lamellar bone with the trabeculae being formed along the pressure trajectories. The most active cells during remodeling are osteoclasts which demineralize the matrix and degrade the organic components by proteinases.7,8 New bone is laid down in its shape, structure and mechanical strength by osteoblasts.7 In summary, the first 1 to 2 weeks, in which inflammation and revascularization occur, seem to be most critical for fracture healing.
6,9 An early formation of granulation tissue could support the differentiation of mesenchymal cells into osteoblasts and thus provide a better requisite for bone remodeling. Coating of orthopedic implants aims at improved bone/implant contact (BIC), reduction of implant loosening and adverse reactions. Since the host response to surgical implants is mediated by regulatory interactions between the cells and the organic extracellular matrix,10-12 coating with components of the extracellular bone matrix (ECM) appears attractive to enhance bone healing around metallic and hydroxyapatite (HA) implants. Thereby, the ECM is not only a passive scaffold for cells.
Several components of the ECM like collagen type I (Coll), chondroitin sulfate (CS) or RGD peptide containing proteins are able to bind cytokines and growth factors12,13 and can interact with bone cells via integrins or other specific cell surface receptors14 thus directly or indirectly influencing migration and cell adhesion as well as proliferation and differentiation of these cells.15,16 Osseointegration is influenced by the primary stability (mechanical stability) and secondary stability (biological stability after bone remodeling) of the implant in the bone. Thereby early bone formation and apposition is essential for secondary stability.17 In this review the promotion of early bone formation by components of the ECM is described. Collagen Type I on Ti and HA Implants Collagen type I is the major structural protein in bone. Coating with Coll enhanced in vitro adhesion, migration and differentiation of osteoblasts on Ti disks.
18,19 Furthermore, the osteoconductive properties of Coll in cancellous and cortical bone are well documented.20-22 Coating of Ti pins with Coll showed that the cellular reaction on the implants appeared more intense around the Coll-coated implants in the early stages of bone healing in a rat tibia model compared with uncoated pins.23,24 At four days after implantation reparative granulation Cilengitide tissue was seen around the Coll-coated implants with 70% of the surface being surrounded by loose granulation tissue.