(397d) Use of a layer-by-layer (LbL) polymer coating technique that forms tunable, modular, nanoscale coatings

Harnessing the synergy between materials at the nanoscale can be a valuable tool in understanding and probing cellular phenomena and in driving specific processes that lead to repair and healing. One method to drive specific cellular process is to use polymers that are biodegradable and capable of serving as carriers of large macromolecules such as proteins. This work explores the use of a layer-by-layer (LbL) polymer coating technique that forms tunable, modular, nanoscale coatings. The process involves the formation of thin films through the alternating adsorption of positively and negatively charged multivalent species at room conditions. Each adsorbed layer in such films can range from 1 to 100 nm, and total therapeutic film thicknesses range from a few hundred nanometers to as much as 10 microns. The LbL technique was used to incorporate a broad range of functional polymers and biomacromolecules.

Polymers of the poly(β-amino ester) family were synthesized using Michael addition between a diacrylate and a primary amine. The polymers are hydrolytically degradable, positively charged and result in amino-acid like breakdown products. By incorporating these polymers in the LbL assembly, controlled release of growth factors was achieved to yield accelerated and highly integrated bone growth and regeneration including demonstrations in a surrogate implant model that illustrate the impact of delivery of these systems from metal implant surfaces for creating bone deposition and integration to achieve high strength bone-implant interfaces. The LbL approach allowed control of both the loading of biologic drug, and the timing of its release from the film. The work demonstrated that it is possible to tune simultaneous release of two drugs, each at different rates. Furthermore, the mechanical properties of the multilayer films, including wear resistance for orthopedic implants demonstrated that the strong cohesive nature of these films. LbL coatings are, by design electrostatically bonded to the surface, and are one to two orders of magnitude thinner while maintaining high loadings of biologic drug, which reduces many of these effective stresses. Very intricate and complex 3D surfaces were coated using the LbL approach, which involved the adsorption of polyions and biologics from very dilute aqueous solution. We have coated the interior pores within macroporous bone scaffolds and nanoporous polymer membranes and demonstrated a corresponding effect on tissue regeneration. This capability to coat porous substrates over a range of thicknesses from micron to centimeter scale allows the coating of a range of polymeric scaffolds with mechanical properties optimized for tissue repair. This work demonstrates the modular nature of LbL, in which the different components will be incorporated and evaluated. The mechanical and release components were isolated, thus enabling controlled release of sufficient factor from the implant surfaces to achieve true bone regeneration throughout the scaffold. 

Collectively, this work provides insight into synthesizing polymeric nano- and maco- materials to probe and modify cellular interactions to control regenerative processes at varying length and time scales. Towards the development of next-generation biomedical therapies this polymerbased approach allows for engineering specific therapies with the ultimate goal to improve
human health.