A Novel Electrospun Dendrimer-Gelatin Hybrid Nanofiber Scaffold for Tissue Regeneration and Drug Delivery
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1094-DD09-07
A Novel Electrospun Dendrimer-Gelatin Hybrid Nanofiber Scaffold for Tissue Regeneration and Drug Delivery Alicia P Smith-Freshwater, Gary L Bowlin, and Hu Yang Department of Biomedical Engineering, Virginia Commonwealth University, Richmond, VA, 23284 ABSTRACT Gelatin has been widely used to develop tissue engineering scaffolds because it has many attractive properties. Dendrimer provides a versatile, compositionally and structurally controlled architecture to construct nanomedicine. This study was aimed at developing a novel electrospun dendrimer-gelatin nanofiber scaffold to best mimic natural extracellular matrix (ECM) to promote tissue formation and serve as a reservoir for controlled drug delivery. Starburst™ polyamidoamine (PAMAM) dendrimer G3.5 was covalently bonded to the gelatin backbone and electrospun into nanofibers. Doxycycline (DC), which is an effective antibiotic that has the ability to inhibit matrix metalloproteinase, was encapsulated into the nanofiber scaffold. The electrospun DC-gelatin scaffold provides a bacterial free environment for cell growth and tissue regeneration. The resulting dendrimer-gelatin nanofiber scaffold achieved a unique structural configuration where covalently bound three-dimensional dendritic nanospheres were evenly distributed along the elongated dimension of the nanofiber, and both dendrimer and gelatin had numerous functional groups suitable for accommodating multiple functional entities and high payload of drugs. The development of this new scaffold with the capability of delivering multiple functional entities was an important step towards the use of bioactive nanofibers to facilitate tissue regeneration and controlled drug release. INTRODUCTION The extended inflammation phase of chronic wounds results in infiltration of excessive amounts of neutrophils at the wound site. Neutrophils produce matrix metalloproteinases (MMP)- destructive proteolytic enzymes [1]. These enzymes degrade the extracellular matrix (ECM), thereby prolonging wound healing. The treatment protocol we proposed involves the fabrication and application of a polymer network of Starburst™ polyamidoamine (PAMAM (G3.5)) dendrimer and therapeutic drugs attached to a gelatin backbone. PAMAM dendrimer has a highly branched structure with easily tailored surface groups. PAMAM dendrimer was chosen because of its versatile drug attachment and powerful drug concentration on a nanoscale level [2]. Doxycycline is an effective antibiotic- with the added ability to inhibit MMPs; thus facilitating wound healing [3]. Gelatin was selected as it is more readily available than collagen. Further, gelatin has many attractive properties as a biomaterial- such as its biological origin, biodegradability, and biocompatibility [4]. Three different types of scaffolds were fabricated for this study: gelatin [100 mg/mL, control], gelatin-dendrimer, and gelatin with encapsulated DC. The primary objective of this study was to identify the critical parameters to fabricate a gelatin wound dressing with optimum fiber si
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