Multifunctional implant surfaces: Surface characterization and bone response to acid-etched Ti implants surface- modified by fibrillar collagen I M. Morra, 1 C. Cassinelli, 1 G. Cascardo, 1 D. Bollati, 1 R. Rodriguez y Baena 2 1 Nobil Bio Ricerche, Portacomaro (AT), Italy 2 Universita ` di Pavia, Dipartimento Discipline Odontostomatologiche, Pavia, Italy Received 12 September 2008; revised 14 April 2009; accepted 28 April 2009 Published online 22 February 2010 in Wiley InterScience (www.interscience.wiley.com). DOI: 10.1002/jbm.a.32702 Abstract: The goal of the study was the evaluation of the effect of biochemical surface modification by collagen on the bone response to acid-etched titanium surfaces. Fibril- lar type I porcine collagen was adsorbed and covalently linked to acid-etched Ti disks and implants. Adhesion, growth, and specific alkaline phosphatase (ALP) activity of osteoblast-like SaOS2 cells were evaluated. Implants in the femur and tibia of rabbit were performed for 2 and 4 weeks and relevant bone to implant contact (BIC) was evaluated by histomorphometry. Results show that cell morphology and growth are controlled by the rough acid- etched implants topography. Specific metabolic activity (ALP) is significantly increased by the collagen overlayer. Importantly, surface modification by collagen increases the speed of periimplant bone formation, resulting in signifi- cantly higher BIC both in femur and tibia at 2 weeks. These results suggest that morphological (surface topogra- phy) and biochemical (surface linking of bioactive mole- cules) cues can cooperate and yield multifunctional implant surfaces. Ó 2010 Wiley Periodicals, Inc. J Biomed Mater Res 94A: 271–279, 2010 Key words: surface modification; surface analysis; titanium surfaces; dental implants; collagen INTRODUCTION Interactions at the bone–titanium implant interface are recognized as the key to osseointegration and an enormous literature on titanium (Ti) surfaces and interfaces exists. 1–3 A huge amount of approaches to the surface modification of titanium to further improve clinical results and extend the spectrum of indications exists as well. Despite wide success and general acceptance, significant research effort is still devoted to the modification of Ti implant surfaces. In particular, the need exists to address difficult clin- ical situations, for example, either an intended implant site compromised because of poor bone quality or grafted bone sites. The latter definition, from a clinical point of view, encompasses for instance low bone density, in the case of highly can- cellous bone, or insufficient quantity of bone (in terms of the width of the alveolar ridge). Traditionally, the approach to surface modification of titanium has been based on the control of surface topography, 3 on ceramic coatings, and, more recently, on physicochemical 4 or inorganic ap- proaches. 5 Presently, a significant research effort is aimed at the biochemical modification of titanium surfaces (BMTiS), that is to the immobilization of proteins, enzymes, or peptides to Ti surfaces for the purpose of inducing specific cell and tissue responses. 6 In contrast to more traditional calcium phosphate coatings, biochemical surface modification utilizes critical organic components of bone to affect tissue response. Among BMTiS, a number of literature reports have been devoted to in vitro and in vivo evaluation of collagen coatings. Collagen, in particular type I collagen, is the most abundant protein in bone, where it makes up approximately 85% of the organic portion. Cellular interactions with collagen have been shown to be important in the regulation of the osteoblast phenotype. Collagen controls adhesion of cells of direct relevance to bone-contacting applica- tions, 7 through the amino acid sequence Arg-Gly- Asp (RGD) it contains. It plays an important role in osteoblast cells behavior, promoting not only cell ad- hesion but also osteoblastic differentiation of bone marrow cells and controlling a number of aspects of their progression along the osteogenic pathway. 8–10 It interacts with critical biomolecules and growth fac- tors, providing the cooperative signaling required for BMPs functioning. 11 It exerts a strong pro-coagulant Correspondence to: M. Morra; e-mail: mmorra@nobilbio.it Ó 2010 Wiley Periodicals, Inc.