Effects of protein molecular weight on the intrinsic material properties and release kinetics of wet spun polymeric microfiber delivery systems Danya M. Lavin a , Linda Zhang a , Stacia Furtado a , Richard A. Hopkins b , Edith Mathiowitz a,⇑ a Department of Molecular Pharmacology, Physiology, and Biotechnology, Center for Biomedical Engineering, Brown University, Providence, RI 02912, USA b Cardiac Regenerative Surgery Research Laboratories of the Ward Center for Congenital Heart Disease, The Children’s Mercy Hospital, Kansas City, MO 64108, USA article info Article history: Received 7 March 2012 Received in revised form 1 August 2012 Accepted 8 August 2012 Available online 16 August 2012 Keywords: Drug-eluting fiber Protein molecular weight Wet spinning PLGA PLLA abstract Wet spun microfibers have great potential for the design of multifunctional controlled release scaffolds. Understanding aspects of drug delivery and mechanical strength, specific to protein molecular weight, may aid in the optimization and development of wet spun fiber platforms. This study investigated the intrinsic material properties and release kinetics of poly(L-lactic acid) (PLLA) and poly(lactic-co-glycolic acid) (PLGA) wet spun microfibers encapsulating proteins with varying molecular weights. A cryogenic emulsion technique developed in our laboratory was used to encapsulate insulin (5.8 kDa), lysozyme (14.3 kDa) and bovine serum albumin (BSA, 66.0 kDa) within wet spun microfibers (100 lm). Protein loading was found to significantly influence mechanical strength and drug release kinetics of PLGA and PLLA microfibers in a molecular-weight-dependent manner. BSA encapsulation resulted in the most sig- nificant decrease in strength and ductility for both PLGA and PLLA microfibers. Interestingly, BSA-loaded PLGA microfibers had a twofold increase (8 ± 2 MPa to 16 ± 1 MPa) in tensile strength and a fourfold increase (3 ± 1% to 12 ± 6%) in elongation until failure in comparison to PLLA microfibers. PLGA and PLLA microfibers exhibited prolonged protein release up to 63 days in vitro. Further analysis with the Kors- meyer–Peppas kinetic model determined that the mechanism of protein release was dependent on Fic- kian diffusion. These results emphasize the critical role protein molecular weight has on the properties of wet spun filaments, highlighting the importance of designing small molecular analogues to replace growth factors with large molecular weights. Ó 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. 1. Introduction Micro- and nanoscale fibers have attracted considerable interest in the field of biomedical engineering [1–5]. In particular, microfi- bers prepared by wet spinning have been used as drug delivery de- vices and tissue engineering scaffolds due to their high surface- area-to-volume ratios for efficient drug release and their ability to be manipulated into a variety of complex macro-level scaffolds. To this end, the use of wet spun fibers as vehicles for drug delivery and biocompatible scaffolds for the assembly of regenerating tissue has been extensively studied. Controlled release of drug molecules has been achieved by encapsulating therapeutics within the poly- mer matrices of wet spun fibers [6–10]. Scaffolds made from a number of wet spun polymers, such as poly(lactic-co-glycolic acid) (PLGA), poly(L-lactic acid) (PLLA), polycaprolactone (PCL), and chitosan have also demonstrated the effectiveness of wet spun microfilaments as morphological guides for tissue regeneration [4,11–14]. Recently, controlled-release technologies and tissue engineer- ing strategies have been combined for the regeneration of tissues, which require a complex sequence of biological cues and structural support [15–18]. Wet spun microfibers have great potential for the design of multifunctional polymeric systems. To date, the majority of research involving wet spun fibers focuses on the release of ther- apeutics or biocompatibility and tissue regeneration capabilities of three-dimensional scaffolds. Little is known about the effects of protein encapsulation on the material properties of wet spun fi- bers. Moreover, studies that have evaluated the mechanical prop- erties of drug-eluting wet spun microfilaments focused only on small molecules (<1 kDa) such as levofloxacin and progesterone, or model proteins of similar molecular weight, such as BSA and ovalbumin [8–10,19]. Textile structures used for ‘‘next generation’’ tissue engineering strategies require structural support and con- trolled delivery of therapeutics with a wide range of molecular weights. In the past, our laboratory has shown that protein molec- ular weight influences drug release kinetics from PLGA micro- spheres [20]. To the best of our knowledge, this effect has yet to be evaluated in a wet spun fiber-based drug delivery platform. The mechanical properties of drug-eluting microfibers are very important to their functionality as therapeutic scaffolds in the clin- 1742-7061/$ - see front matter Ó 2012 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved. http://dx.doi.org/10.1016/j.actbio.2012.08.005 ⇑ Corresponding author. Tel.: +1 401 863 1358; fax: +1 401 863 1595. E-mail address: edith_mathiowitz@brown.edu (E. Mathiowitz). Acta Biomaterialia 9 (2013) 4569–4578 Contents lists available at SciVerse ScienceDirect Acta Biomaterialia journal homepage: www.elsevier.com/locate/actabiomat