A wide variety of metals, ceramics, and polymers are used for bone implants in many different applications including joint replacement, fracture fixation, and tissue augmentation subsequent to tumour surgery [1]. The bone-biomaterial interaction may be significantly different for all these materials. For load-bearing implants the superior fracture and fatigue resistance has made metals the materials of choice up to the present [2]. Development is proceeding on polymers, ceramics, composites, and biologically derived materials such as collagen, but suitable alternatives for general use have yet to be introduced [2]. Thus, this paper will focus on current materials in the “state of...

The placement of an implant at its implant site is the beginning of a series of complex processes in both time and space [1, 2]. Some of these are inflammatory processes that occur as a consequence of the local surgical trauma [3–5], macroscopic transport processes, and molecular reactions at the material-tissue interface [1, 6, 7]. Some involve cell activity and how it is stimulated by the new situation. One may have to worry about how the surgical procedure [8] and the load on and motion of the implant [9] influence the healing process. Microbial infections [10] or material corrosion...

A strongly adherent, mechanically bonded interface develops between certain inorganic implant materials and bone; this is well established. [1–17, 34]. The materials on which such a bonded interface forms are calledbioactive. The mechanical strength of the bonded interface has been shown, subject to testing methods, to equal or exceed that of the bone with which the bioactive implant is bonded [6, 12, 17–19, 34]. For a few glass compositions the bioactivity is sufficiently high and the rate of bonding sufficiently rapid that a strongly adherent bond will also form with soft tissues [20–23]. The tissue bonding...

To determine the biocompatibility of a biomaterial, it is important to understand the phenomena at the interface between the biomaterial and the biological system into which the material is to be implanted. At such an interface, the molecular constituents of the biological system meet and interact with the molecular constituents of the surface of the biomaterial [1]. Since these interactions occur primarily on the molecular level and in a very narrow interface zone having a width of less than 1 nm [2], surface properties on the atomic scale, in particular the composition and structure of the surface layer of the...

During implantation, titanium releases corrosion products into the surrounding tissue and fluids [1, 2] even though it is covered by a thermodynamically stable oxide film. Physical properties of the oxide such as passivity, stoichiometric composition, defect density, crystal structure and orientation, surface defects, and impurities have been suggested as factors determining biological performance [3]. Therefore, identifying the mechanisms that control the performance of titanium in vivo necessitates measurement of the physical chemistry changes in the material surface.

We propose that an understanding of such interactions will be gained from systematic in vitro modeling. Thus, the objective of this chapter is...

Calcium phosphate is a major component of biological minerals. There is therefore considerable interest in the elucidation of the mechanisms of crystallization, dissolution, and transformation of calcium phosphates. This is a complex issue not only because of the numerous solid phases that may be involved, but also because of the presence of multiple components in the solution media. Although the thermodynamically most stable phase, hydroxyapatite (HA), is generally used as the model compound for biological minerals, other phases such as amorphous calcium phosphate (ACP), dicalcium phosphate dihydrate (DCPD), and octacalcium phosphate (OCP), as well as defect apatites, may participate [1,2]....

“Chemical bonding” of bioactive implants with bone is thought to be responsible for the direct bone attachment to implants and for the interfacial strength which prevents interfacial fracture. In contrast, bioinert implants do not form such “bonding”; there is no direct attachment to bone and the interfacial strength is low enough to allow fracturing to occur at the interface [1,2]. Bioinert materials include inert ceramics (e.g., alumina), metals, and polymers. Bioactive materials include bioactive glass ceramics and calcium phosphate materials [1–4]. The interface between bone and bioactive materials has been described as a “bonding zone,” “amorphous zone,” or “electron...

The importance of the ultrastructure at the interface between an implant and its adjacent tissue has become increasingly recognized as a rate-controlling factor in the area of biomaterials. There is a need to resolve details at an atomic or lattice plane level to establish the continuity of the interface and hence its potential long-term stability.

High-resolution transmission electron microscopy (TEM) allows characterization of a material on a microscale in terms of the morphology and structure resulting from biochemical and crystallographic reorganization at the interface. Earlier attempts reported in the literature dealt with examination of individual materials which came into contact...

Since the introduction of dissociative extraction procedures almost 10 years ago the majority of the major proteins of the mineralized bone matrix have been isolated and characterized. A number of these proteins are known to be derived from tissue fluids and appear to be concentrated in bone tissue through their affinity for hydroxyapatite (HA). However, those proteins in bone that are synthesized by osteoblasts are believed to be important, not only in the formation of the organic matrix, but also in the formation, growth, and regulated dissolution of the HA crystals. Several of the osteoblast-derived proteins are either unique to...

Cellular interactions at material surfaces are complex molecular processes that just now are being scrutinized. These associations closely resemble cell-substratum relationships of in vitro cell culture systems in that they are mediated through several different families of receptors at the cell-polymer surface interface. In addition to directing cell adhesion to specific extracellular matrices and ligands on adjacent cells, these receptor interactions modulate various aspects of cell behavior including growth, differentiation, protein production, and stress tolerance [1–3].

The initial event in the utilization of almost all biomedical polymers involves adsorption of blood and plasma proteins onto the material surfaces [4]....

Dental implants have proved to be highly successful in clinical use [1]. However, at present, implant placement requires the utmost attention to surgical technique. Failing to do so will generally prevent effective osseointegration and promote instead fibrous encapsulation and, thus, failure of the implant. An additional problem relates to the placement of implants into thin trabecular bone. Such tissue might not provide the firm support required for successful implantation. Finally, an essential element of the osseointegration process requires that loading of an implant not take place until maximal bone ingrowth into the implant has occurred. [It should be pointed out...

Matrix proteins in bone and dentin have been considered to play a crucial role in the calcification and architectural construction of these hard tissues [1]. The structure and function of some matrix proteins in bone formation have been revealed. Obviously, collagen is the best-known protein among them for its role in calcification, and it is most widely known through the hole-zone theory [1]. Non-collagenous proteins, too, such as osteocalcin [2, 3], osteonectin [4], and phosphophoryn [5, 6], have been shown to have roles in the regulation of calcification [see also Sodek et al. ch. 9 herein]. Recently, however, biochemists have...

Shell and bone are intriguing examples of how biological organisms process thin film and composite materials. Although rather mundane and limited materials are used, the microstructures of the biominerals greatly surpass those of many man-made high-technology materials in both control and sophistication. Mineral crystals are formed at low temperature with high degrees of orientation, specific morphologies, high-density packing, and specific polymorphs selected. Figure 13.1 depicts a cross section of the nacre layer in a gastropod shell showing alternating mineral and polymer layers, and highly oriented aragonite crystals [1]. These properties are very desirable in man-made ceramic materials such as thin...

Davies: I would like to bring us back to biological reality and away from fracture toughness measurements. We are here to discuss the interface, and, while I don't want to pre-empt the next session which is on cell activity on surfaces, we have had a lot of intimation so far that cells will do certain things; bone cells will mineralize and create their matrix in response to certain biochemical factors, for example. We have heard a lot about mineralization in chemical experiments from solution on artificial surfaces or material surfaces. I think the question we ought to be addressing is:...

An ideal implant system in bone permits the transfer of load, remains stable in place, and does not provoke any negative local or systematic tissue effects during the lifetime of the patient. Since a biomaterial is “a non-viable material used in a medical device, intended to interact with biological systems,” [1] the properties of both the material and the tissue have to be evaluated. An understanding of the interactive events taking place in the interface zone between the implant and the recipient tissue will play a central role in this evaluation. Despite the fact that different biomaterials have been used...

Non-alloyed titanium has been used clinically for more than 25 years as an implant material for anchorage of, for example, dental bridges to the jaw bones [1]. For the past 7 years it has also been used for percutaneous anchorage of both hearing aids and auricular or facial prostheses to the skull [2]. These implant applications have shown good clinical results and been associated with very few infections [3–5]. To what degree these results are due to specific features of the implant material per se is not clear since the clinical procedures are also distinguished by, for instance, the...

The past two decades have witnessed the development of biomaterials with surface chemical or biomechanical properties that would be expected to promote bone formation. An example of a material with specialized surface chemistry is the bioactive glass devised by Hench and co-workers [1]. An example of a surface that has a specific biomechanical advantage is the porous-coated system developed at the University of Toronto [2] which integrates tissues closely in a three-dimensional interlocking system. Although it is generally recognized that surface topography is an important factor in implant performance, few systematic investigations of this characteristic have been undertaken, and it...

A variety of chemical, physical, and cellular reactions take place on implantation of bone substitute biomaterials. In order to gain a better understanding of reactions which occur at the biomaterial interface, correlations need to be made between osteoblast-specific behaviour and known variations in the physicochemical surface properties of the material.

The chemical groups and ions at the surface of a biomaterial determine its surface charge and bonding potential. The adsorption of ions, molecules, and macromolecules at biomaterial surfaces will be of variable strength, which will also influence their desorption, a process likely to continue throughout the lifetime of an implant....

The embryonic development and the repair of bone both follow the same pattern of cellular and molecular events involving the commitment and differentiation of osteogenic cells from progenitor cells. It was previously hypothesized that osteoblasts multiplied at a bone fabrication site to provide sufficient cells to synthesize the new bone required. Recent observations clearly indicate that a series of cellular and molecular transitions exist from progenitor cell to a non-mitotic, secretory osteoblast; the osteoblast functions to lay down and mineralize the matrix of bone. These transitions are outlined in Fig. 18.1 which summarizes the observations of Scott Bruder in which...

Many materials have the structural properties to function as implants but lack the necessary biocompatibility or bioactivity, and many materials have excellent biological properties but lack the mechanical properties necessary to serve as stress-bearing implants. Some implants interface with more than one tissue and it is likely that the different surfaces of the implant will require a different material to achieve optimal material-cell interface. It is our belief that the ideal dental implant will display three material surfaces: one to interface with bone, one to interface with epithelial tissue, and a third surface to discourage bacterial plaque formation. This philosophy...

Bone is a dynamic living tissue which undergoes formation and resorption throughout life. Conventional wisdom holds that osteogenesis proceeds by the elaboration of a non-mineralized collagenous matrix, osteoid, which subsequently calcifies. This is largely true. However, the formation of bone tissue, while brought about by the synthetic activity of a single cell type – the osteoblast – is discontinuous. This discontinuity is expressed histologically by the presence of both resting and reversal lines. These two morphological structures are quite different. First, resting lines represent the temporary reduction in, or cessation of, activity of differentiated osteoblast populations which results in the...

Morphogenetic movements and wound healing processes at least require cell adhesion, migration, and proliferation. They are controlled by extracellular matrix components which are not only structural supports, but also signals for the regulation and integrity of subsequent tissue.

The extracellular matrix can be divided into two major groups: the basement membranes and the interstitial connective tissue. The former possess a sheet-like structure, whereas the latter is made of varying cells (fibroblasts, odontoblasts, osteoblasts), depending on the tissue type, which are embedded in a matrix composed of collagens, proteoglycans, and glycoproteins. The biological activities of the extracellular matrix molecules are expressed...

The implantation into skeletal tissues of orthopaedic devices used for total joint arthroplasty is accompanied by a complex sequence of cellular and biochemical processes. Numerous studies have outlined these events and have helped to show that the composition, surface topography, and mechanical properties of the implant biomaterial are among the factors which determine the nature of the tissue reaction at the implant site [1–10]. Unique host factors may further modify the nature of the response, particularly with respect to metal implants containing nickel, cobalt, or chromium which have been associated with focal immune responses suggestive of apparent “allergic” reactions...

A detailed understanding of the response of bone tissue to the surface of implanted materials is dependent on a baseline understanding of normal tissue responses in simpler situations. It is tempting to hypothesize that the response to implanted materials could be approximated as the sum of two independent stimuli. The first would be the injury to the tissue at the time of implantation, and the second would be the surface characteristics of the implanted material.

Our group has used histological and molecular techniques to investigate the response of bone to injury. We have correlated changes in the histology of the...

An increasing array of biological and synthetic materials is available to surgeons for reconstructing osseous defects. Among them, fresh autogenous bone grafts are preferred because of their compatibility and efficacy, the ideal graft being a viable portion of autogenous bone that maintains mechanical and cellular functions in the new location.

The advent of massive and complex reconstructive procedures in orthopaedic and craniofacial surgery highlights the limitations of harvesting autogenous bone [1]. These limitations include the time required for the harvesting procedure, its associated morbidity, and the inadequate amount of transplantable osteogenic bone, particularly in infants, children, and frail adults [2]....

This chapter is concerned with the generation of bone or connective tissue in response to beads with surfaces that are negatively or positively charged. The potential use of positively charged beads to foster formation of soft-connective tissue and promote wound healing is discussed. Similarly, the potential application of negatively charged beads to defective or normal sites, to promote osteogenesis and thus bony repair or augmentation in the skeleton will be described.

Poor surgical wound healing, non-healing leg ulcers, and pressure sores comprise a national health problem particularly in malnourished, diabetic, irradiated, or vascularly compromised individuals. In view of the severity...

The surface characteristics and chemical reactivity of artificial materials which may contribute to the interface created upon implantation in a biological milieu have received much attention (see Smith ch. 1, Kasemo and Lausmaa, ch. 2; Hench, ch. 3, and Hanawa, ch. 4 herein). In the case of bone-substitute materials, generally two groups can be defined: first, those which permit biological bonding of bone to their surfaces, so-called bioactive materials, and second, those which apparently do not (for general review see [1]). While ultrastructural studies of tissues processed from both in vivo and in vitro experiments have provided convincing morphological evidence...

Bone-bonding biomaterials are of special use in reconstructive surgery because of their good integration capacity with bone. The available bone-bonding materials comprise several calcium phosphate ceramics like hydroxyapatite (HA) [1, 2], tricalcium phosphate [3–5], tetracalcium phosphate [6] and fluoroapatite [7, 8] together with Bioglass [9] and glass ceramics [10]. Each of these bone-bonding materials is substantially stiffer than bone and most are relatively brittle. These properties limit the surgical use of bone-bonding materials; indeed, several surgical disciplines would benefit from an elastomeric bone-bonding biomaterial.

Elastomeric properties are predominantly found with polymers, which, as it seems, unfortunately do not bond...

We have recently presented both general considerations for and examples of bone bonding and epithelial attachment to surfaces of implant materials [1]. We showed that the tissue (host) and the material responses were both time dependent and influenced by not only the physical and chemical properties of the implant but also the cellular responses in the implantation bed. Reports indicate that there are numerous parameters that are able to influence host and material responses. These include biomechanical factors [2–5], the solubility of the material, the chemical composition of material released from an implant, the implant surface morphology [6–8],...

Biomaterials which create chemical and mechanical bonds with bone include (1) non-porous materials with or without a hydroxyapatite (HA) coating [1–6], (2) porous materials with or without an HA coating [7–10], (3) non-bioactive bone cement such as PMMA cement, and (4) bioactive bone cement [11–13].

A common problem with the cementless fixation of an artificial bone and joint is that some patients complain of pain on weight-bearing. This is because a complete initial fixation is not obtained and micromotion of the component may occur. Porous metal with HA coating is found to be better than that without...

In the past, orthopaedic prostheses such as hip and knee replacements relied on acrylic cement for attachment and fixation to bone. Tissue reaction to this cement has been implicated in the failure of these implants due to loosening. Consequently, newer prostheses have been designed to dispense with cement altogether and instead utilize materials that actively encourage the direct apposition and attachment of bone to the surface of the implant. Various materials and surface coatings believed to be biocompatible or bioactive with surrounding intramedullary bone are being used in new implant designs that rely on either porous ingrowth or direct biologic...

Bone substitute biomaterials are usually classified as either bioactive or non-bioactive materials. Bioactive materials are known to bond with bone [1], while the non-bioactive materials are not thought to exhibit such a property. Despite this, it is commonly said that osseointegration [2], contact osteogenesis [3], or fibrous encapsulation [4] occurs depending on the kinds of non-bioactive materials. Several reports have compared the interfaces of bone and different biomaterials [3–6]. However, differences between the types of bone bonding, osseointegration, and contact osteogenesis, have not been clarified.

The present chapter compares push-out data from five kinds of bone substitutes, including both...

The first investigator to suggest the possibility of a direct bone contact with a metallic material was P.-I. Brånemark in his classic paper of 1969 [1]. In those days there were no methodological approaches that allowed for sectioning through intact metal to bone specimens. Therefore, the assumption of a soft-tissue-free interface had to be based on indirect evidence obtained from histological sections after removing the implant from its bone site. It was difficult to state with absolute certainty that a thin soft-tissue coat was not removed together with the implant during this procedure, which was the probable reason that some...

An understanding of the biological processes occuring at the bone-implant interface could contribute significantly to improving prosthesis design and post-operative patient management strategies. The body's regenerative response at the site of surgical trauma involves skeletal and connective tissue differentiation and regulation, the same processes occurring in fracture healing [1,2]. These regenerative processes also display many of the tissue differentiation features observed during skeletal growth and morphogenesis [3, 4].

Two important environmental factors which influence the overall process of skeletal tissue differentiation are (a) tissue oxygen tension, which is related to vascularity, and (b) the mechanical loading history of the tissue,...

A necessary condition for bone ingrowth with porous coated, bone interfacing implants is the avoidance of excess movement of the implant relative to the host bone during the early healing phase after implantation. Studies have shown that under conditions of limited early loading and, hence, minimal relative movement of implant and bone, “rigid” implant fixation can be achieved through bone formation within the pores of the surface coating in a period of 3 to 4 weeks (Fig. 34.1). This assumes that certain other conditions are satisfied such as the use of biocompatible materials and a coating with sufficiently large pore...

Concern with extensive bone loss following implantation of stiff metallic stems in cementless total hip arthroplasty has led to investigative use of stems of lower stiffness [1,2]. One of the goals is to reduce the stress-protecting effects of the prosthesis on the cortical bone and, therefore, to reduce cortical atrophy. The use of materials with a lower elastic modulus than that of the metals currently in use is one approach to reducing stress-shielding. For this purpose, the materials of most promise are polymers from which composite femoral stems can be manufactured [3,4].

One question to be addressed is whether or...

The primary function of the bone-biomaterial interface is to provide safe and effective load transfer from implant to bone. This biomechanical function is obvious for load-bearing orthopaedic and oral/maxillofacial implants, since their success clearly depends on secure mechanical fixation at the interface. Failure of interfacial fixation, or loosening, is still a leading cause of implant failure [1, 2]. Therefore, in terms of basic science and practical engineering design, a key question is: What variables and underlying mechanisms determine events at the bone-biomaterial interface?

Regrettably, a complete answer to this question is not yet available. The wide variety of fixation rationales,...

The interfacial bonding strength between a new material and bone has usually been evaluated using transcortical femoral push-out testing in animals [1]. However, the transcortical model for evaluating the bonding strength between an implant and cortical bone under non-load-bearing conditions does not represent the clinical status of a bone-implant interface which is exposed to dynamic and intermittent stresses for a long period. For the purpose of simulating the dynamic conditions occurring at the bone-implant interface, we have implanted several biomaterials with different surface characteristics at the load-bearing site of the knee joint of dogs, and evaluated their bone-bonding capability.

Bead-Coated...

Kasemo: I am quite confused about the role of load and micromotion in bone healing, and I would ask the collected expertise to give me some help here. It’s obvious to me that the healing interface would be damaged if you have too much motion. You basically have an interface that can take certain motion which gives rise to elastic deformation. If you stay within that limit of elastic deformation the material would probably not be perturbed very much. But if you go beyond that motion you will create real physical ruptures and you will damage the system. That’s very...

The interface between biomaterial and tissue is the specific location of interaction during implant function. If a device is removed for some reason other than interface dysfunction, critical information can be obtained from qualitative and quantitative studies of the interaction zone. Basic theories of a proposed application can be tested; however, limitations of available records and a complex synergism of material and host responses must be recognized in order to minimize misinterpretations. This chapter will present (1) an overview of concepts from the biomaterial and biomechanical sciences, (2) examples of implant interface evaluations, and (3) a summary of the usefulness...

Knowledge of the structure and composition of interfacial tissue is necessary for an understanding of the mechanisms by which biomaterials and tissue interact. At present this knowledge is in many respects rudimentary. In this context studies of metal implants, retrieved from patients or used experimentally, are important. One reason for this is that metal and metal alloys are widely used, often very successfully, as implants in various clinical applications. Another reason is that the material and surface properties of metal implants can be analyzed in great detail and also modified in a systematic manner [1, 2], which makes such implants...

A layer of fibrous tissue usually develops between bone and a prosthetic implant regardless of whether this is cemented or uncemented. [The implied distinction here between, for example, the orthopaedic and dental fields is quite important. In the case of dental implants, fibrous encapsulation is usually synonymous with clinical failure. It should also be noted that the majority of reports in the orthopaedic literature concern failed, rather than successful, implants. – Ed.] This fibrous tissue layer has come to be known as the “fibrous membrane,” particularly in the orthopaedic literature [1–4]. It contains macrophages which are present as a...

Late failure of cemented primary and revision total joint replacements is most commonly due to aseptic loosening [1, 2]. Contributing to this loosening may be purely mechanical or technical factors or abnormal mechanical stresses in the artificial joint [3, 4]. Loosening of the prosthesis may result in the production of significant wear debris which may contain polymethylmethacrylate (PMMA) cement, high-density polyethylene, or metal fragments. The wear material commonly is associated with a significant foreign body macrophage and giant cell response in the fibrous membrane lying between bone and cement. A similar reaction is seen in the fibrous capsule of the...

The traditional choices of prostheses for arthroplasty following hip fracture are not entirely suitable. For example, the Moore and Thompson prostheses give rise to many problems, some of which are directly related to the use of acrylic cement. Intraoperative death and severe, sometimes fatal, hypotension are reported and loosening of the stem, frequently due to failure of the cement coating, may occur in up to 35% of the cases. As the latter is less well tolerated in elderly patients, we have introduced prostheses with hydroxyapatite (HA) coated stems, which we currently use for all our patients.

The prosthesis is a...

Davies: The first session of this meeting was about surfaces and high-tech methods of looking at surface characteristics of materials. Some of the subsequent sessions have been about high-tech biology, about how we can examine the biological component of the interface which we can manipulate in the laboratory. Dr Lemons, you have probably done more retrievals than anybody else and you have probably the largest program of retrievals that I know of. Does retrieval analysis – or do you think retrieval analysis will be able to – provide some guidelines for the basic scientists around the table on what characteristics...

Kenley: Genetics Institute is about a ten-year-old genetic engineering company which makes human Pharmaceuticals from recombinant proteins. My colleagues and I develop drug delivery systems, vehicles that will be used to administer new drugs in an appropriate clinical setting. We have probably all seen that opportunities arise when there is a melding of two really quite disparate technologies, and the example here is very good: materials scientists and biologists coming together to address the concept of the bone-biomaterial interface. However, what I and, I think, others are seeing here is a really unique situation in that we have a developing...