(198c) Nanolayered Staged Delivery Approaches to Wound Healing  and Bone Regeneration

The biological proesses involved in wound healing and tissue regeneration, as well as the progression of a number of diseases, take place in stages that involve the release or presentation of distinct molecules and the chemical and physical signaling that ensues. Ideally one would be able to modulate the release of chemokines, growth factors, or siRNA and DNA that regulate genes that regulate such factors, to facilitate tissue regeneration in-situ. The use of alternating layer-by-layer (LbL) assembly enables a modular platform that can control release of therapeutics over a broad range of time scales, from several seconds to multiple months. We have developed systems that can address a range of different wound healing needs by taking advantage of this tunable platform and the ability to incorporate drugs programmed to release at a range of different rates and with staged release behavior. The nature of the layering process enables the incorporation of different drugs within different regions of the thin film architecture; the result is an ability to uniquely tailor both the independent release profiles of different therapeutics from the same film, and the order of release of molecules to targeted regions of the body. The staging of release of multiple growth factor proteins can achieve the regeneration of collagen and remodeling of tissue in wounds at appropriate time points to facilitate wound closure and tissue vascularization. Moreover, multilayered release coatings as thin as a half micron to several microns can be designed to deliver different growth factor proteins or siRNA and other biologic drugs directly to wounds to correct the dysregulation of wound healing processes that have gone awry, from burn and scar tissue to the closure of chronic wounds such as diabetic ulcers. These approaches are also applicable to the regeneration of bone in critical defects and for orthopedic applications.