Nanobiotechnology approaches to design better dental implant materials.
Subject: Implant dentures
Authors: Krishna, Kumar U
Ramesh, Bhat T.R.
Harish, P.V.
Sameer, V.K.
Gangaiah, M.
Pub Date: 01/01/2011
Publication: Name: Trends in Biomaterials and Artificial Organs Publisher: Society for Biomaterials and Artificial Organs Audience: Academic Format: Magazine/Journal Subject: Health Copyright: COPYRIGHT 2011 Society for Biomaterials and Artificial Organs ISSN: 0971-1198
Issue: Date: Jan, 2011 Source Volume: 25 Source Issue: 1
Accession Number: 308129318
Full Text: Introduction

Nanotechnology dates back to 1959 when the late Nobel Prize winning physicist Richard P. Feyman speculated the potential of nanosized devices. Nanotechnology involves the use of materials with components that have dimensions of less than 100nm. Better dental implant materials are required since, frequently implant materials are not compatible with bone cells responsible for bone formation, but rather they promote the formation of undesirable soft connective tissues which ultimately leads to loosening and eventually implant failure. This review article discusses recent studies that have been conducted to suggest that nanophase materials can be synthesized to possess nanometer dimensions to components of bone tissue to promote new bone formation, compared with conventional implant materials.

Approaches to design better implants based on molecular and biochemical aspect of cellular recognition of cellular implant surface

To design better dental implant materials, one should concentrate on cellular process that leads to efficient new growth formations. Specific proteins like fibronectin and vitronectin in biological fluid such as blood plasma mediate the adhesion and growth of desirable and undesirable cells on an implant surfaces [1]. Some studies have provided evidence that surface energies, surface chemical composition and surface features determined by pore size and topography influences the type and concentration of adsorbed proteins [2]. Previous studies have shown that fibronectin adsorb on calcium phosphate coated bioactive glass compared with untreated bioactive glass [3]. It is well recognized that osteoblast adhere to specific amino acid sequences such as arginine-glycine-aspartic acid, and heparin sulphate binding regions in adsorbed proteins [4]. Some studies have reported specific collagen mimetic amino acid sequence which stimulates specific expression of alpha 2 and beta 1 integrin receptors in osteoblast cell membranes to enhance alkaline phosphatase activity and matrix mineralization [5]. Underwood and colleagues demonstrated that calcium treated vitronectin adsorbed on polystyrene possessed a more bioactive conformation that enhanced osteoblast function compared with other materials [6].

Approaches to design better implants based on topography and biomaterial chemistry to promote bone formation

Human bone is assembled from nanosized organic and mineral phase into large architectures, specifically calcium phosphate crystallites which are similar to hydroxyapatite compositionally and structurally are nanomaterials. In addition other proteins in the extracellular matrix of bone are nanostructured similar to type 1 collagen fibers.

Specifically compared with smooth surface, micron surface roughness <10[micro]m of titanium substrate created by sand blasting, etching, machining and use of micron size metal bead coatings has been reported to enhance osteoblast function such as adhesion, proliferation, production of alkaline phosphatase and deposition of calcium containing mineral on implant surface [7,8]. Improved osteoinduction of titanium was observed on micro porous structure compared with nonmicroporous titanium which did not induce bone formation at all [9]. Instead of formulating surface with microroughness, emphasis should be placed on techniques that create nanometer roughness. Several studies have reported improved osseointegration on nanophase surface created from a wide range of chemistry than conventional materials. Price and colleagues showed that alumina nanometer fibers which are more structurally similar to calcium phosphate crystals and collagen fibers found in natural bone stimulated osteoblast response such as adhesion, alkaline phosphatase activity and calcium deposition than compared with conventional grain size alumina. This study also demonstrated increased osteoblast function on alumina nanofibers compared with alumina nanosphere. The importance of nanofibers for bone regenerations has been demonstrated in additional studies. Natural bone consists of hard nanostructured hydroxyapatite in a nanostructured protein based soft hydrogel template which is mostly collagen. For this reason, nanostructure hydroxyapatite has been an intriguing coating materials on traditionally used titanium for improving implant application.

The helical rosette nanotubes which form through the self assembly process of deoxy-nucleci acid base pair building blocks in body solutions are soft nanotubes with helical architecture that mimics natural collagen. Helical rosette nanotubes are novel organic nanotubes formulations that mimic the dimensions of the nanostructure of bone components [10]. The objective of invitro study by Thomas J Webster was to combine the promising attributes of helical rosette nanotubes and nanocrystalline hydroxyapatite on titanium and assess osteoblast functions. Different sizes of nanocrystalline hydroxyapatite were synthesized in this study through a wet chemical precipitation process following either hydrothermal treatment or sintering. Transmission electron microscopy images showed that helical rosette nanotubes aligned with nanocrystalline hydroxyapatite with a high affinity between both components. Some of the nanocrystalline hydroxyapatite formed dense coating with helical rosette nanotubes on titanium. More importantly results demonstrated enhanced osteoblast adhesion on helical rosette nanotubes and hydroxyapatite coated titanium compared with conventional uncoated titanium. Recent studies have demonstrated that the adsorption and conformation of proteins that mediate specific osteoblast adhesion are enhanced on nanophase material [11].

Woo and colleagues reported that 3D nanofibers scaffold selectively adsorb more proteins including fibronectin and vitronectin compared with solid pore wall consisting of poly L-lactic acid [12]. This led to increased osteoblast function on nanofibrous scaffold. One of the main reasons why nanophase material attract selective proteins to their surface is due to their altered surface energetic compared with conventional materials. More over studies have highlighted altered proteins bioactivity when adsorbed to nanophase compared with conventional materials. It is thought that the bioactivity of selective proteins is altered on nanophase materials due to greater wettability and surface features close to size of proteins.

Surface properties are changed when grain size is reduced into the nanometer, Wen and colleagues measured grain boundary volume percentage with grain size ranging from 2um to 2nm [13]. As expected they found greater numbers of grain boundaries at the surface of nanophase compared with conventional materials. In addition compared with large grain counterparts, nanophase materials possessed higher surface area and altered electron distributions [14]. Since proteins are charged molecules such properties will change surface energetic to influence protein interactions that mediate cell adhesion. Webster and colleagues demonstrated that aqueous contact angles were 3 times smaller when alumina grain size was decreased from 167 to 24nm [15]. They also reported that adsorption of vitronectin which stimulates osteoblast adhesion increased on nanophase ceramic with greater wettability [16]. Moreover, when vitronectin adsorbed on nanophase ceramic it was unfolded to a larger extent than on conventional ceramic to expose larger numbers of osteoblast adhesive epitopes in absorbed proteins. Similar increased unfolding and exposure of osteoblast adhesive epitopes was demonstrated for fibronectin on nanophase ceramics [17].

Kay and colleagues demonstrated that titania nanosized particle embedded in poly lactic Dco Dglycolic acid promoted osteoblast adhesion compared with conventional sized titania in poly lactic Dco- glycolic acid [18]. Poly lactic-co-glycolic acid containing nano particles of titania were more hydrophilic than those containing conventional titania. This trend of enhancing osteoblast function by creating more wettable surface through the use of nanophase materials holds good for metal as well. Osteoblasts deposited more calcium on hydrophilic nanometer metal surface than compared with conventional titanium or cobalt-chromium-molybdenum alloy. Interestingly osteoblasts adhered at metal particle boundaries when metal nanosize grain was less than 1 [micro]m [19].

Study highlighting the Importance of nanometer roughness was conducted by Price and Colleagues [20], importantly their study demonstrated increased osteoblast adhesion on polymer casts of the nanophase carbon fibers compared with polymer casts of conventional carbon fibers [21]. Polymer casts of composites of polycarbonate urethane/carbon nanotubes also promoted osteoblast function compared with casts of conventional carbon tubes. Webster and colleagues found that nanometer surface roughness on nanophase ceramic improved both osteoblastic and osteoclastic responses while simultaneously inhibiting fibroblast function. Greater osteoblast deposition of calcium containing mineral and the number of resorption pits created by osteoclast correlated with increased nanometer surface roughness ranging from 17 to 20 nm for alumina [22]. Supporting evidence of decreased fibroblast function on nanophase ceramics has been presented by Mustafa and colleagues who suggested that ceramic with increasing surface roughness decreased initial fibroblast adhesion compared with smooth surface [23]. Similar study have been reported for poly lactic-co-glycolic acid of the same surface chemistry but altering only in degrees of nanometer surface roughness 50-100nm [24]. Washburn and colleagues demonstrated that osteoblastic cells reduced proliferation and possibly increased differentiation into calcium depositing cells on polymer nanotopographics greater than 1.1nm [25].

Dalby and colleagues have also indicated the importance of nanometer surface structure in controlling cell function.

Specifically they reported that island of 95nm in height decreased fibroblast proliferation compared with those of 13nm in height on a copolymer mixture of polystyrene and polybromostyrene [26]. In a subsequent study the authors suggested that fibroblast changed their cytoskeleton arrangement on island in the nanometer regime which suppressed spreading and formation of confluent cell layers [27]. Another study has suggested that smooth muscle cell numbers were greater on nanometer compared with conventional roughness values, thus adding validity that nanometer surface features may influence a wide range of cell functions [28].

Studies by Theresa and colleagues has provided evidence that electron beam evaporation can modify implant surface specifically polyethylene and titanium to have nano structure surface features to improve osteoblast and endothelial cell adhesion [29]. Few studies have reported increased osteoblast adhesion by ionic plasma deposition method. Bhattarai and co-workers found that the matrix with chitosan polyethylene oxide ratio of 90:10 retained excellent integrity of fibrous structure in water. Experimental results from cell stain assay and scanning electron microscope imaging showed that the nanofibrous structure promoted the attachment of human osteoblasts and chondrocytes.


It may be observed that significant evidence now exists elucidating that nanophase materials represent an important growing area of research that may improve bonding between an implant and surrounding bone. With tremendous amount of information available concerning bone cell interaction with nano structured surfaces that will most certainly aid in improving dental implant efficacy.


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Krishna Kumar U, Ramesh Bhat T.R, Harish P.V., Sameer V.K., Gangaiah M

Department of Prosthodontics including Crown and bridge and Implantalogy. Rajarajeshwari Dental College and Hospital, Bangalore. Corresponding author, ( Krishna Kumar U.

This review article discusses the following key issues--Synthesis of nanomaterials that mimic the size of constituent components of bone for dental implant applications. Increased functions of osteoblast on nanophase compared with conventional ceramics, metals, polymers etc. Decreased functions of competitive cells on nanophase compared with conventional materials.

Received 14 December 2010; Accepted 2 March 2011; Available online 5 March 2011
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