Surface roughness dependent osteoblast and fibroblast response on poly(L-lactide) films and electrospun membranes Clarisse Ribeiro, 1,2 * Vitor Sencadas, 1,3 * Anabela C. Areias, 1 F. Miguel Gama, 4 Senentxu Lanceros-M endez 1,2 1 Centro/Departamento de F  ısica da Universidade do Minho, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal 2 INL—International Iberian Nanotechnology Laboratory, 4715-330 Braga, Portugal 3 Instituto Polit ecnico do C avado e do Ave, Campus do IPCA, 4750-810 Barcelos, Portugal 4 IBB–Institute for Biotechnology and Bioengineering, Centre of Biological Engineering, Universidade do Minho, Campus de Gualtar, 4710-057 Braga, Portugal Received 14 September 2014; revised 21 October 2014; accepted 29 October 2014 Published online 11 November 2014 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/jbm.a.35367 Abstract: Poly(L-lactide) electrospun mats with random and aligned fiber orientation and films have been produced with degrees of crystallinity ranging from 0 up to nearly 50%. The overall surface roughness is practically constant irrespective of the sampling areas (1 3 1 mm to 20 3 20 mm) for degrees of crystallinity below 30%, increasing for higher degrees of crystallinity for the larger sampling areas. Further, due to fiber confinement, surface roughness variations are smaller in electrospun mats. Samples with 50% of crystallinity show the lowest osteoblast and the highest fibroblast proliferation. Therefore, it is verified that higher roughness promotes lower osteoblast but higher fibroblast proliferation. The overall results indicate the rele- vant role of the sub-microenvironment variations associ- ated to the microscale roughness in determining the different cell responses. V C 2014 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 103A: 2260–2268, 2015. Key Words: poly(l-lactic acid), tissue and biomedical engi- neering, cell-material interface How to cite this article: Ribeiro C, Sencadas V, Areias AC, Gama FM, Lanceros-M endez S. 2015. Surface roughness dependent osteoblast and fibroblast response on poly(L-lactide) films and electrospun membranes. J Biomed Mater Res Part A 2015:103A:2260–2268. INTRODUCTION Cell/material interactions are a key issue for cell biology studies and biomedical applications. It has been reported that cell response is sensitive to material topography and functional characteristics, leading to specific cellular responses. 1–4 Thus, mechanisms associated to cell adhesion, migration, spreading, and differentiation can be controlled by tailoring physical properties, surface chemistry, mechani- cal properties, micro, and nanostructure. 5,6 Cells attachment to membranes or scaffolds via local adhesion points, con- necting the cytoskeleton to the polymer surface, is affected by surface chemistry 7 (e.g., presence of ligands), electro- static charge, 8 wettability (surface polarity), 9 mechanical properties, 10 and surface topography. 7 In this sense, under- standing cell-biomaterial interaction is critical in order to design novel successful biomaterials with increased and tai- lored functionality for applications such as wound healing, immune response, and tissue integration. Surface roughness may be considered on different scales (e.g., nano or micrometric), each level of surface patterning potentially impacting the cell-material interactions. Wash- burn et al. 11 reported on osteoblast response to polymer degree of crystallinity. Samples with a gradient of crystallin- ity were prepared and it was shown that cells are sensitive to topographic features of the order of 5 nm. Further, the observed inhibition of proliferation of cells was not influ- enced by changes in adherent proteins but directly ascribed to changes in substrate roughness. Tissue in-growth through porous scaffolds composed of semicrystalline or amorphous PLA implanted in rat mesentery 12 lead also to the conclu- sion that cell proliferation is adversely affected by substrate roughness, reporting a reduction of tissue in-growth Additional Supporting Information may be found in the online version of this article. *These authors contributed equally to this work. Correspondence to: S. Lanceros-Mendez; e-mail: lanceros@fisica.uminho.pt Contract grant sponsor: the Portuguese Foundation for Science and Technology (FCT); contract grant numbers: C/FIS/UI607/2011, PTDC/ CTM-NAN/112574/2009 Contract grant sponsor: FCT; contract grant numbers: SFRH/BPD/63148/2009, SFRH/BPD/90870/2012 Contract grant sponsor: Matepro—Optimizing Materials and Processes, Programa Operacional Regional do Norte, Quadro de Refer^ encia Estrat egico Nacional” (QREN), “Fundo Europeu de Desenvolvimento Regional” (FEDER); contract grant number: NORTE-07–0124-FEDER-000037 2260 V C 2014 WILEY PERIODICALS, INC.