Targeted Drug Delivery from Titanium Implants: A Review of Challenges and Approaches.

Titanium implants are considered the gold standard of treatment for dental and orthopedic applications. Biocompatibility, low elasticity, and corrosion resistance are some of the key properties of these metallic implants. Nonetheless, a long-term clinical failure of implants may occur due to inadequate osseointegration. Poor osseointegration induces mobility, inflammation, increased bone resorption, and osteolysis; hence, it may result in painful revision surgeries. Topographical modifications, improvement in hydrophilicity, and the development of controlled-release drug-loading systems have shown to improve cellular adhesion, proliferation, and differentiation. Surface modifications, along with drug coating, undoubtedly demonstrate better osseointegration, especially in challenged degenerative conditions, such as osteoporosis, osteoarthritis, and osteogenesis imperfecta. Anabolic bone-acting drugs, such as parathyroid hormone peptides, simvastatin, prostaglandin-EP4-receptor antagonist, vitamin D, strontium ranelate, and anti-catabolic bone-acting drugs, such as calcitonin, bisphosphonates, and selective estrogen receptor modulators, expedite the process of osseointegration. In addition, various proteins, peptides, and growth factors may accessorize the idea of localized therapy. Loading these substances on modified titanium surfaces is achieved commonly by mechanisms such as direct coating, adsorption, and incorporating in biodegradable polymers. The primary approach toward the optimum drug loading is a critical trade-off between factors preventing release of a drug immediately and those allowing slow and sustained release. Recent advances broaden the understanding of the efficacy of adsorption, hydrogel coating, and electrospinning layer-by-layer coating facilitated by differential charge on metallic surface. This review discusses the existing approaches and challenges for the development of stable and sustained drug delivery systems on titanium implants, which would promote faster and superior osseointegration.