(136h) Nanolayer Multi-Therapy Scaled Delivery from Implant Surface

One of the important problems in the field of orthopedic medicine is the ability to create a stable bone-materials interface with an implant. The most effective treatment requires the delivery of exacting amounts of therapeutics of different types over appropriate timeframes in and around the implant, while maintaining mechanical integrity of the implant materials and allowing for bone integration on their surfaces. This work presents a novel next-generation implant coating for both eradication of an established biofilm within the bone cavity and accelerated bone repair via the controlled delivery of antibiotic and growth factor in sequence from stable nanometer-scale coatings on the implant surface.

Infection is the most common reason for complications, which often lead to complete removal of implants (74%). Infection significantly increases morbidity, and places huge financial burdens on the patient and the healthcare systemâ??projected to exceed $1.6 billion/year by 2020. Because infection is much more common in implant replacement surgeries, these issues greatly impact long-term patient care for a growing population. For revision arthroplasty of an infected prosthesis, a prolonged and expensive two-stage procedure requiring two surgical steps and a 6â??8 week period of joint immobilization is todayâ??s gold standard. A single-stage revision is preferred as an alternative; however, traditional bulk polymer systems such as bone cement cannot load sufficient amounts of therapeutic to eradicate existing infection, are insufficient or infeasible for the release of sensitive biologic drugs that considerably aid in bone regeneration, and lead to substandard mechanical properties and retarded bone repair.

These issues are addressed by conformal, programmable, and degradable dual therapy coatings (~500 nm thick) in a layer-by-layer fashion using the enabling nanofabrication tool of electrostatic multilayer assembly. The nanolayered construct allows large loadings of each drug, thus enabling ultrathin film coatings to carry sufficient treatment and precise independent control of release kinetics and loading for each therapeutic agent. The coating architecture was designed to enable both early burst and lower sustained release of antibiotics sufficient to eliminate infection, and a long-term sustained release of BMP-2 growth factor to induce more significant and mechanically competent bone formation than a short-term burst release. In rats, the successful growth factor-mediated osteointegration of the multilayered implants with the host tissue improved bone-implant interfacial strength by 15-fold when compared with the bare implant control, and yields a mechanical bond 17-fold higher than that created with the use of clinically available bioactive bone cement.

Here we focused on dual delivery of an antibiotic and a growth factor owing to the urgent need for enhanced infection-reducing and tissue-integrating strategies in orthopedic applications, but the excellent modularity of multilayers for incorporation and release of diverse therapeutics suggests this approach should be also applicable to different implant applications such as vascular graft and artificial heart implants for which the risks of infection are often ignored. Our findings demonstrate the potential of this layered release strategy to introduce a durable implant solution, ultimately an important step forward in the design of biomedical implant release coatings for multiple medical applications.