Implants are medical devices used to replace, support, or enhance biological structures in the body. They are being applied very diversely in many current medical treatments of, for example, neurological or cardiovascular disorders but they are still most commonly used in modern dentistry and orthopedics. Implants are traceable to ancient Egyptian and South American civilization. During the millennia of their successful use, a plethora of materials have evolved and have often been replaced by improved substances. Materials as diverse as stone, gold, ivory, wood, rubber, acrylic, and Bakelite have been used in the manufacture of prosthetic implants. In modern times, however, metallic alloys are the preferred choice since clinical studies have demonstrated that implants made from iron, cobalt, chromium, titanium, and tantalum can be used safely and effectively in the manufacturing of orthopedic implants that are left in vivo for extended periods of time. In particular, titanium (Ti)-based alloys have excellent properties for use in porous forms for biologic fixation of prostheses. The most common is Ti-6 aluminum-4 vanadium (Ti6Al4V), but other more modern alloys are coming into use as well. Titanium's high level of biocompatibility, low level of corrosion, and modulus of elasticity close to that of bone allow for its use in numerous porous implants that have yielded excellent long-term results of precise implant fit.
Bone metabolism
The success of Ti implants is intimately related to the degree of bone integration, i.e., the direct structural and functional connection between living bone and the surface of an implant. This process is influenced by the initial attachment, proliferation, and differentiation of the bone-forming cells called osteoblasts at the implant-bone interface. Also, protein adsorption onto Ti implant surfaces is directly influenced by surface characteristics of the implants and the establishment of a conditioning film which governs cellular responses, production of key local factors such as prostaglandins, and, consequently, bone remodeling. Prostaglandins are enzymatically derived metabolites of polyunsaturated fatty acids, such as arachidonic acid. Prostaglandin E
2 (PGE
2) in particular is the most widely produced prostanoid in the human body and has diverse actions on various organs, including inflammation, bone healing, and bone formation. Prostaglandins, including prostaglandin E
1, PGE
2 and prostaglandin F
2α, have been demonstrated to stimulate both bone resorption and bone formation but in favor of bone formation, thus, increasing bone mass and bone strength. Endogenous PGE
2 increases locally after fracture and the inhibition of PGE
2 production impairs bone healing. In contrast, the local administration of PGE
2 stimulates bone formation and callus development in animal models.
Implant surface
The most important parameters regarding the biological effects Ti implants can elicit in the bone are the surface topography and physico-chemistry. Generally, hard tissue-derived cells (e.g. osteoblast-like cells) preferentially attach to moderately rough surfaces rather than smooth surfaces
in vitro and also exhibit higher osteogenic differentiation than on smooth surfaces. In addition to topographical variations, the roles of surface chemistry and wettability in modulating cellular behaviors is also gaining significant interest. Scientists were able to show that osteoblasts cultured on hydrophilic Ti surfaces exhibited a more differentiated phenotype and that hydrophilic surfaces were beneficial to the creation of an osteogenic microenvironment with an increased secretion of PGE
2 and transforming growth factor (TGF)-β1. Accordingly, surface modifications of Ti implants are routinely conducted these days to achieve desired biological responses and enhance the reliability of Ti bone integration.
Bone integration
In their recent study,
Shu-Fen Chu and colleagues from the Taipei Medical University in Taiwan, analyzed features of different Ti surface modifications using laser treatments (denoted as L
50-Ti), evaluated its effects on the responses of osteoblast-like MG-63 cells, and compared them to polished surfaces (P-Ti) and sandblasted and acid-etched surfaces (SLA-Ti). Their investigations showed a continuous increase in cell numbers after seeding MG-63 cells on the differently treated surfaces. However, MG-63 cells grown on L
50-Ti surfaces displayed significantly higher proliferation rates compared to those cultured on P-Ti and SLA-Ti surfaces. In addition, alkaline phosphatase activity and osteocalcin levels were greater on the rougher SLA-Ti and L
50-Ti surfaces than on P-Ti surfaces, indicating that SLA-Ti and L
50-Ti surfaces provided better conditions for osteoblast differentiation. By using Enzo’s
PGE2 ELISA kit, the authors of this study could also show that the level of this important autocrine/paracrine regulatory factor of bone metabolism, bone formation, and eventually bone healing, increased in MG-63 cells with incubation time, and that L
50-Ti surfaces, in particular, exhibited the highest PGE
2 production levels over the entire observation period with the strongest effects during early onset of bone integration. These findings indicate that micro-/nanoporous Ti surfaces with hydrophilic properties such as produced by laser treatments may provide a valuable alternative to future development of Ti implants.
From our complex portfolio in
metabolic research to our large portfolio of
Eicosanoid ELISA Kits and
Prostaglandin-related products, Enzo Life Sciences provides a complete set of tools for studying bone metabolism, some of which are described below.