J Mater Sci: Mater Med (2006) 17:1043–1048 DOI 10.1007/s10856-006-0442-x Skeletal tissues as nanomaterials L. Bozec · M. A. Horton Received: 5 October 2005 / Accepted: 2 February 2006 C  Springer Science + Business Media, LLC 2006 Abstract Collagen is the most abundant protein in the body and, though the ﬁbre-forming collagens have a ‘common’ structure, it is adapted to perform a large range of functions— from the differing mechanical needs of tendon versus bone to forming a transparent support structure in the cornea. This perﬁdy also suggests that collagen could form a generic basis for a range of scaffold needs for tissue engineering or medi- cal device coating applications. We at the London Centre for Nanotechnology—a joint venture between University Col- lege London and Imperial College—are taking a bottom-up approach having decided that many of the ‘accepted dog- mas’ of collagen biology may not be quite as soundly based as currently held. We are using several of the tools of ‘hard’ nanotechnology—such as atomic force microscopy—to re- examine collagen structure with the longer term aim of using such information to design materials with appropriate phys- ical attributes. Examples of our current research on miner- alised and soft tissue collagens are presented. 1 Introduction Skeletal tissues, such as bone, are continually modiﬁed by cellular processes in growth, in response to systemic hormones such as oestrogen, and following changes in the mechanical stress to which the skeleton is exposed during everyday life. Bone can be considered as a self-modifying, nano-structured composite material comprising at least two components. The protein part, mainly type I collagen, forms L. Bozec · M. A. Horton () The Department of Medicine, University College London, London WC1E 6JJ, UK and the London Centre for Nanotechnology, University College London, London WC1E 6BT, UK e-mail: m.horton@ucl.ac.uk a model for the subsequent deposition of calcium phosphate mineral, hydroxyapatite. The material is ‘living’ and can be considered to be ‘smart’ as it self-adapts its structure by way of the function of two types of cells: osteoclasts and osteoblasts. Thus, mineralised bone is removed by osteo- clasts during skeletal growth, and in repair after, for example, bone fracture. Calcium is dissolved by cell-mediated acidi- ﬁcation of the extra-cellular space, and collagen is degraded following release from osteoclasts of proteolytic enzymes such as cathepsin K. Protein-containing extracellular matrix is then laid down by osteoblasts and this subsequently min- eralises. Similar processes occur upon eruption of primary and permanent teeth, during the course of orthodontic tooth movement, or in diseases where the substance of the tooth is damaged. Likewise, tendon is a collagenous tissue that adapts its structure to functional requirements during growth and exposure to differing mechanical strains during exercise; during evolution, adaptive pressures have led to the genera- tion of specialised tendon structure much as occurred for the skeleton [1]. There have been a number of reports on atomic force mi- croscopy (AFM) imaging of mineralised tissues. Mineral and collagen have been studied in bone following artiﬁcial re- moval of calcium using mild acidiﬁcation or chelation with EDTA [2–4]. We have only found one report [5] where the consequences of osteoclastic resorption upon a mineralised substrate in vitro have been examined—however, therein, AFM was only used as a metrology tool to measure the depth of resorption lacunae. We have reported on the purposeful use of osteoclast cell cultures to remove mineral and hence ex- pose collagen for subsequent analysis [6]. Tooth structure has also been examined, generally evaluating the effect of acidi- ﬁcation on enamel structure in the context of dental disease [7, 8]. There is also a substantial body of literature exam- ining the detailed structure of the collageneous extracellular Springer