Effect of electrospun fiber diameter and alignment on macrophage activation and secretion of proinflammatory cytokines and chemokines.

Macrophage activation can be modulated by biomaterial topography according to the biological scale (micrometric and nanometric range). In this study, we investigated the effect of fiber diameter and fiber alignment of electrospun poly(L-lactic) (PLLA) scaffolds on macrophage RAW 264.7 activation and secretion of proinflammatory cytokines and chemokines at 24 h and 7 days. Macrophages were cultured on four different types of fibrous PLLA scaffold (aligned microfibers, aligned nanofibers, random microfibers, and random nanofibers) and on PLLA film (used as a reference). Substrate topography was found to influence the immune response activated by macrophages, especially in the early inflammation stage. Secretion of proinflammatory molecules by macrophage cells was chiefly dependent on fiber diameter. In particular, nanofibrous PLLA scaffolds minimized the inflammatory response when compared with films and microfibrous scaffolds. The histological evaluation demonstrated a higher number of foreign body giant cells on the PLLA film than on the micro- and nanofibrous scaffolds. In summary, our results indicate that the diameter of electrospun PLLA fibers, rather than fiber alignment, plays a relevant role in influencing in vitro macrophage activation and secretion of proinflammatory molecules.

[1]  S. Grinstein,et al.  Phagocytosis , 2011, Current Biology.

[2]  J. Edwards,et al.  Exploring the full spectrum of macrophage activation , 2008, Nature Reviews Immunology.

[3]  J. Babensee,et al.  Macrophage and dendritic cell phenotypic diversity in the context of biomaterials. , 2011, Journal of biomedical materials research. Part A.

[4]  G. Sui,et al.  Poly(L-lactic acid)/hydroxyapatite hybrid nanofibrous scaffolds prepared by electrospinning , 2007, Journal of biomaterials science. Polymer edition.

[5]  J. Takahara,et al.  IL-13 as well as IL-4 induces monocytes/macrophages and a monoblastic cell line (UG3) to differentiate into multinucleated giant cells in the presence of M-CSF. , 1998, Biochemical and biophysical research communications.

[6]  S. Agarwal,et al.  Use of electrospinning technique for biomedical applications , 2008 .

[7]  Y. Lee,et al.  Collagen scaffolds derived from a marine source and their biocompatibility. , 2006, Biomaterials.

[8]  David C. Martin,et al.  The design of electrospun PLLA nanofiber scaffolds compatible with serum-free growth of primary motor and sensory neurons. , 2008, Acta biomaterialia.

[9]  Buddy D. Ratner,et al.  Biomaterials Science: An Introduction to Materials in Medicine , 1996 .

[10]  Kam W Leong,et al.  Synthetic nanostructures inducing differentiation of human mesenchymal stem cells into neuronal lineage. , 2007, Experimental cell research.

[11]  D. Williams,et al.  Immune response in biocompatibility. , 1992, Biomaterials.

[12]  Feng-Huei Lin,et al.  Release characteristics and bioactivity of gelatin-tricalcium phosphate membranes covalently immobilized with nerve growth factors. , 2005, Biomaterials.

[13]  L. Fassina,et al.  In vitro enhancement of SAOS-2 cell calcified matrix deposition onto radio frequency magnetron sputtered bioglass-coated titanium scaffolds. , 2010, Tissue engineering. Part A.

[14]  Nikolaj Gadegaard,et al.  Nanotopographical control of human osteoprogenitor differentiation. , 2007, Current stem cell research & therapy.

[15]  Vera A. Schulte,et al.  Surface topography induces fibroblast adhesion on intrinsically nonadhesive poly(ethylene glycol) substrates. , 2009, Biomacromolecules.

[16]  K. Leong,et al.  The role of electrospinning in the emerging field of nanomedicine. , 2006, Current pharmaceutical design.

[17]  James M. Anderson,et al.  The topographical effect of electrospun nanofibrous scaffolds on the in vivo and in vitro foreign body reaction. , 2009, Journal of biomedical materials research. Part A.

[18]  E. Entcheva,et al.  Electrospun fine-textured scaffolds for heart tissue constructs. , 2005, Biomaterials.

[19]  A. Zucchelli,et al.  An innovative and versatile approach to design highly porous, patterned, nanofibrous polymeric materials , 2009 .

[20]  S. Ramakrishna,et al.  A review on electrospinning design and nanofibre assemblies , 2006, Nanotechnology.

[21]  M. Govoni,et al.  Electrospun Scaffolds of a Polyhydroxyalkanoate Consisting of ω-Hydroxylpentadecanoate Repeat Units: Fabrication and In Vitro Biocompatibility Studies , 2010, Journal of biomaterials science. Polymer edition.

[22]  S. Ramakrishna,et al.  Characterization of the surface biocompatibility of the electrospun PCL-collagen nanofibers using fibroblasts. , 2005, Biomacromolecules.

[23]  G. Bowlin,et al.  Modulation of murine innate and acquired immune responses following in vitro exposure to electrospun blends of collagen and polydioxanone. , 2009, Journal of biomedical materials research. Part A.

[24]  N. Ziats,et al.  Interleukin-4 inhibits tumor necrosis factor-alpha-induced and spontaneous apoptosis of biomaterial-adherent macrophages. , 2002, The Journal of laboratory and clinical medicine.

[25]  C. E. Stiles,et al.  Tissue response to single-polymer fibers of varying diameters: evaluation of fibrous encapsulation and macrophage density. , 2000, Journal of biomedical materials research.

[26]  Benjamin Chu,et al.  Functional electrospun nanofibrous scaffolds for biomedical applications. , 2007, Advanced drug delivery reviews.

[27]  S. Sbrana,et al.  In vitro evaluation of the PEtU-PDMS material immunocompatibility: the influence of surface topography and PDMS content , 2009, Journal of materials science. Materials in medicine.

[28]  G. Bowlin,et al.  Electrospinning of collagen/biopolymers for regenerative medicine and cardiovascular tissue engineering. , 2009, Advanced drug delivery reviews.

[29]  David G Simpson,et al.  Utilizing acid pretreatment and electrospinning to improve biocompatibility of poly(glycolic acid) for tissue engineering. , 2004, Journal of biomedical materials research. Part B, Applied biomaterials.

[30]  Andreas Greiner,et al.  Electrospinning: a fascinating method for the preparation of ultrathin fibers. , 2007, Angewandte Chemie.

[31]  J. Anderson,et al.  Biomaterial biocompatibility and the macrophage. , 1984, Biomaterials.

[32]  I. Lemaire,et al.  M‐CSF and GM‐CSF promote alveolar macrophage differentiation into multinucleated giant cells with distinct phenotypes , 1996, Journal of leukocyte biology.

[33]  G. Sui,et al.  Poly-L-lactic acid/hydroxyapatite hybrid membrane for bone tissue regeneration. , 2007, Journal of biomedical materials research. Part A.

[34]  S. Ramakrishna,et al.  Electrospinning of nano/micro scale poly(L-lactic acid) aligned fibers and their potential in neural tissue engineering. , 2005, Biomaterials.

[35]  J. Anderson,et al.  Interleukin-13 induces human monocyte/macrophage fusion and macrophage mannose receptor expression. , 1997, Journal of immunology.

[36]  B D Ratner,et al.  Relative influence of polymer fiber diameter and surface charge on fibrous capsule thickness and vessel density for single-fiber implants. , 2003, Journal of biomedical materials research. Part A.

[37]  D. Grainger,et al.  Cell-cell signaling in co-cultures of macrophages and fibroblasts. , 2010, Biomaterials.

[38]  R. Franke,et al.  Stimulation of monocytes and macrophages: possible influence of surface roughness. , 2008, Clinical hemorheology and microcirculation.

[39]  Mahmoud Ahmadian,et al.  Design and evaluation of basic standard encryption algorithm modules using nanosized complementary metal–oxide–semiconductor–molecular circuits , 2006 .

[40]  J. Anderson,et al.  Human monocyte/macrophage activation and interleukin 1 generation by biomedical polymers. , 1988, Journal of biomedical materials research.

[41]  L. Yahia,et al.  Biocompatibility of novel polymer-apatite nanocomposite fibers. , 2008, Journal of biomedical materials research. Part A.

[42]  Joshua C. Hansen,et al.  Effect of surface nanoscale topography on elastic modulus of individual osteoblastic cells as determined by atomic force microscopy. , 2007, Journal of biomechanics.

[43]  D. Grainger,et al.  Macrophage Serum-Based Adhesion to Plasma-Processed Surface Chemistry is Distinct from That Exhibited by Fibroblasts. , 2006, Plasma processes and polymers.

[44]  Hae-Won Kim,et al.  Electrospun materials as potential platforms for bone tissue engineering. , 2009, Advanced drug delivery reviews.

[45]  Jacqueline A. Jones,et al.  Characterization of topographical effects on macrophage behavior in a foreign body response model. , 2010, Biomaterials.

[46]  Jessica D. Schiffman,et al.  A Review: Electrospinning of Biopolymer Nanofibers and their Applications , 2008 .

[47]  David G Simpson,et al.  Measuring fiber alignment in electrospun scaffolds: a user's guide to the 2D fast Fourier transform approach , 2008, Journal of biomaterials science. Polymer edition.

[48]  R. Simmons,et al.  TNF and IL-1 generation by human monocytes in response to biomaterials. , 1992, Journal of biomedical materials research.

[49]  G. Bowlin,et al.  Angiogenic potential of human macrophages on electrospun bioresorbable vascular grafts , 2009, Biomedical materials.

[50]  Weiyuan John Kao,et al.  The interrelated role of fibronectin and interleukin-1 in biomaterial-modulated macrophage function. , 2007, Biomaterials.

[51]  G. Bowlin,et al.  In vitro evaluations of innate and acquired immune responses to electrospun polydioxanone-elastin blends. , 2009, Biomaterials.

[52]  Sing Yian Chew,et al.  The application of nanofibrous scaffolds in neural tissue engineering. , 2009, Advanced drug delivery reviews.

[53]  Ruo-Pan Huang Cytokine protein arrays. , 2004, Methods in molecular biology.