Surface-Mediated Bone Tissue Morphogenesis from Tunable Nanolayered Implant Coatings

Abstract

The functional success of a biomedical implant critically depends on its stable bonding with the host tissue. Aseptic implant loosening accounts for over half of all joint replacement failures. Various materials, including metals and plastic, confer mechanical integrity to the device, but often these materials are not suitable for direct integration with the host tissue, which leads to implant loosening and patient morbidity. We describe a self-assembled, osteogenic, polymer-based conformal coating that promotes stable mechanical fixation of an implant in a surrogate rodent model. A single modular, polymer-based multilayered coating was deposited using a water-based layer-by-layer approach, by which each element was introduced on the surface in nanoscale layers. Osteoconductive hydroxyapatite (HAP) and osteoinductive bone morphogenetic protein 2 (BMP-2) contained within the nanostructured coating acted synergistically to induce osteoblastic differentiation of endogenous progenitor cells within the bone marrow, without indications of a foreign body response. The tuned release of BMP-2, controlled by a hydrolytically degradable poly(β-amino ester), was essential for tissue regeneration and, in the presence of HAP, the modular coating encouraged the direct deposition of highly cohesive trabecular bone on the implant surface. The bone-implant interfacial tensile strength was significantly higher than standard bone cement, did not fracture at the interface, and had long-term stability. Collectively, these results suggest that the multilayered coating system promotes biological fixation of orthopedic and dental implants to improve surgical outcomes by preventing loosening and premature failure.

The Application of Nanotechnology for Implant Drug Release

“…Wadagaki et al, for example, demonstrated that the synthetic molecule simvastatin could be incorporated into electrospun nanofi bers that were deposited into a scaffold and that the subsequent release of simvastatin enhanced the formation of bone in vivo [ 105 ]. Shah et al used a chitosan/poly aspartic acid LbL nanofi lm system to load the osteoinductive bone morphogenetic protein 2 (BMP2) and hydroxyapaptite onto durable implants made of PEEK or titanium [ 106 ]. The inclusion of a hydrolytically cleavable molecule in the fi lms enabled tuning the BMP2 release and the coatings promoted bone regeneration in vitro and in vivo.…”

Adaptive growth factor delivery from a polyelectrolyte coating promotes synergistic bone tissue repair and reconstruction

“…Importantly, PEM assembly uses mild, aqueous conditions that preserve the activity of fragile biologics. We have previously demonstrated the importance of controlling the release of biologics from multilayer films by introducing the therapeutic as a layer during the PEM assembly process (15). Lack of toxicity is critical for materials used in implantable devices, and the long-term host response to permanent implants continues to be a concern.…”

“…The coating consisted of a micrometer-scale polyelectrolyte multilayer (PEM) thin film composed of layers of BMP-2 and PDGF-BB growth factors and may be adapted to release nanograms of growth factor per square millimeter for extended and physiologically meaningful time periods for bone healing by endogenous progenitor cells. Our previous studies have demonstrated that we can easily apply the PEM coatings to any substrate of choice, which can be other orthopedic polymers such as polycaprolactone and polyether ether ketone, metals such as titanium, and calcium phosphates (14)(15)(16)(17). To demonstrate the efficacy of this approach, we chose to coat a well-studied biodegradable porous poly(lactic-co-glycolic) acid (PLGA) membrane with well-understood physicochemical properties.…”

Implantatoberflächen und ihr Einfluss auf das periimplantäre Hartgewebe

“…In allen anderen Gruppen gab es eine hohe Variabilität in der Knochenbildung und die maximalen Level wurden nicht gehalten [96]. Beschichtungen mit eingebautem BMP können auch aus synthetischen Polymeren wie dem hydrolytisch abbaubaren Poly(ß-aminoester) bestehen, der BMP2 ebenfalls langsam freisetzt und eine Steigerung der Resistenz gegen Zugkräfte an der Knochen-Implantat-Grenzfläche zeigte [97]. Eine andere Möglich-keit sind natürlich vorkommende Polymeren wie Chitosan, wobei sich eine Beschichtung aus Chitosan/Silikat/BMP auf porösem Titan ebenfalls günstig auf die Knochenbildung im Kaninchenmodell auswirkte [98].…”