Advances in Bioceramics and Porous Ceramics VI
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Ceramics VI
A collection of 13 papers from The American Ceramic Society’s 37th International Conference on Advanced Ceramics and Composites, held in Daytona Beach, Florida, January 27-February 1, 2013. This issue includes papers presented in Symposium 5 - Next Generation Bioceramics and Biocomposites and Symposium 9 - Porous Ceramics: Novel
Developments and Applications.
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Advances in Bioceramics and Porous Ceramics VI - Roger Narayan
Preface
This issue contains the proceedings of the Next Generation Bioceramics
and Porous Ceramics: Novel Developments and Applications
symposia of the 37th International Conference and Exposition on Advanced Ceramics and Composites (ICACC’13), which was held from January 27th to February 1st, 2013 in Daytona Beach, Florida, USA.
A rapidly growing area of ceramic science and technology involves the development of novel ceramic materials that enhance the diagnosis or treatment of medical conditions. Bioinspired and biomimetic ceramics, which imitate attributes of materials found in nature, have also stimulated significant interest in the bioceramics community. The Next Generation Bioceramics
symposium addressed several areas related to processing, characterization, modeling, and functionality of bioceramic materials. Topics covered by the symposium included advanced processing of bioceramic materials, bioinspired and biomimetic ceramic materials, biomineralization, self-assembled bioceramic materials, inorganic-organic composite materials, nanoscale bioceramic materials, mechanical properties of bioceramic materials, in vitro and in vivo characterization of bioceramic materials, bioceramic materials for drug delivery, bioceramic materials for gene delivery, bioceramic materials for sensing, and bioceramic materials for dental applications. This symposium promoted numerous productive discussions among various groups in the bioceramics community, including academic researchers, governmental researchers, industrial researchers, and graduate students.
The Porous Ceramics
symposium collected contributions from several research groups around the world involved in the development, characterization, and application of ceramic components possessing a large volume of porosity. People attending the symposium were able to appreciate how researchers are now increasingly able to tailor the characteristics of the porosity embedded in ceramic parts, including the total porosity, the average cell size, the cell size distribution, and the degree of interconnectivity among the cells. In particular, a joint session with Symposium 8 entitled Rapid Prototyping of Porous Ceramics
highlighted how innovations in the processing of porous architectures can lead to improved properties and innovative features. Much effort is also being devoted to the precise characterization and quantification of porosity, together with the use of modeling tools to predict the behavior of porous components.
Papers on a wide range of topics were given, including innovations in processing methods, structure and properties, modeling and novel characterization tools, mechanical behavior, micro- and meso-porous ceramics, ceramic membranes, and applications of porous ceramics. The joint session with Symposium 5 entitled Porous Bioceramics
enabled the attendees to acquire insights into the requirements for porous components used in biological applications. This joint session highlighted the importance of collaborations and cross-fertilization of ideas among scientists specializing in different disciplines. The quality of the oral and poster presentations and the good attendance at every session are a testimony to the large interest that exists in the ceramics community, both in academia and in industry, for porous ceramics because of their unusual characteristics and widespread applicability.
We would like to thank the staff at The American Ceramic Society, including Greg Geiger, Mark Mecklenborg, Marilyn Stoltz, and Marcia Stout, for making this proceedings volume possible. We would also like to thank Anita Lekhwani and her colleagues at John Wiley & Sons for their support of this volume. In addition, we would like to acknowledge the efforts of the contributors and reviewers, without whom this volume would have not been possible. We also thank the officers of the Engineering Ceramics Division of The American Ceramic Society, including Michael Halbig, Sanjay Mathur, Tatsuki Ohji, Dileep Singh, and Mrityunjay Singh, and the 2013 Program Chair, Sujanto Widjaja, for their tireless efforts. We hope that this volume becomes a beneficial resource for academic and industrial efforts involving porous ceramic materials and bioceramic materials. Finally, we hope that this volume contributes to advances in ceramic science and technology and signifies the leadership of The American Ceramic Society in these emerging areas.
ROGER NARAYAN
University of North Carolina and North Carolina State University
PAOLO COLOMBO
Università di Padova (Italy) and The Pennsylvania State University
Introduction
This issue of the Ceramic Engineering and Science Proceedings (CESP) is one of nine issues that has been published based on manuscripts submitted and approved for the proceedings of the 37th International Conference on Advanced Ceramics and Composites (ICACC), held January 27—February 1, 2013 in Daytona Beach, Florida. ICACC is the most prominent international meeting in the area of advanced structural, functional, and nanoscopic ceramics, composites, and other emerging ceramic materials and technologies. This prestigious conference has been organized by The American Ceramic Society’s (ACerS) Engineering Ceramics Division (ECD) since 1977.
The 37th ICACC hosted more than 1,000 attendees from 40 countries and approximately 800 presentations. The topics ranged from ceramic nanomaterials to structural reliability of ceramic components which demonstrated the linkage between materials science developments at the atomic level and macro level structural applications. Papers addressed material, model, and component development and investigated the interrelations between the processing, properties, and microstructure of ceramic materials.
The conference was organized into the following 19 symposia and sessions:
The proceedings papers from this conference are published in the below nine issues of the 2013 CESP; Volume 34, Issues 2-10:
Mechanical Properties and Performance of Engineering Ceramics and Composites VIII, CESP Volume 34, Issue 2 (includes papers from Symposium 1)
Advanced Ceramic Coatings and Materials for Extreme Environments III, Volume 34, Issue 3 (includes papers from Symposia 2 and 11)
Advances in Solid Oxide Fuel Cells IX, CESP Volume 34, Issue 4 (includes papers from Symposium 3)
Advances in Ceramic Armor IX, CESP Volume 34, Issue 5 (includes papers from Symposium 4)
Advances in Bioceramics and Porous Ceramics VI, CESP Volume 34, Issue 6 (includes papers from Symposia 5 and 9)
Nanostructured Materials and Nanotechnology VII, CESP Volume 34, Issue 7 (includes papers from Symposium 7 and FS3)
Advanced Processing and Manufacturing Technologies for Structural and Multi functional Materials VII, CESP Volume 34, Issue 8 (includes papers from Symposium 8)
Ceramic Materials for Energy Applications III, CESP Volume 34, Issue 9 (includes papers from Symposia 6, 13, and FS4)
Developments in Strategic Materials and Computational Design IV, CESP Volume 34, Issue 10 (includes papers from Symposium 10 and 12 and from Focused Sessions 1 and 2)
The organization of the Daytona Beach meeting and the publication of these proceedings were possible thanks to the professional staff of ACerS and the tireless dedication of many ECD members. We would especially like to express our sincere thanks to the symposia organizers, session chairs, presenters and conference attendees, for their efforts and enthusiastic participation in the vibrant and cutting-edge conference.
ACerS and the ECD invite you to attend the 38th International Conference on Advanced Ceramics and Composites (http://www.ceramics.org/daytona2014) January 26–31, 2014 in Daytona Beach, Florida.
To purchase additional CESP issues as well as other ceramic publications, visit the ACerS-Wiley Publications home page at www.wiley.com/go/ceramics.
SOSHU KIRIHARA, Osaka University, Japan
SUJANTO WIDJAJA, Corning Incorporated, USA
Volume Editors
August 2013
Bioceramics
CERAMICS FOR HUMAN HEALTH CHALLENGES
Larry L. Hench¹ and Mike Fenn²,³,⁴
¹ Department of Materials Science and Engineering
² Department of Biomedical Engineering
³ Center for Applied Optimization
⁴ Particle Engineering Research Center
University of Florida, Gainesville, Florida, USA
INTRODUCTION
First and Second Generation Biomaterials
The first Engineering Ceramics Summit organized by the American Ceramic Society in 2011 led to the conclusion that three of the top ten technologies needed to transform the world were in the field of healthcare. The objective of this paper is to provide an update of some critical needs to meet the challenges of affordable healthcare for an aging population. The role of third generation bioactive ceramics for patient specific tissue regeneration therapies to meet this challenge is discussed. The first step in understanding this challenge is to recognize the sequence of developments in the field of bioceramics. The goal of all biomaterials is to Achieve a suitable combination of physical properties to match those of the replaced tissue with a minimal toxic response in the host
.¹ By 1980 there were more than 50 implanted prostheses in clinical use made from 40 different materials. At that time more than 3 million prosthetic parts were being implanted in patients worldwide each year. A common feature of most of the 40 materials used in implants during the first three decades of development from the ‘60s to ‘80s was biological inertness
. The principle underlying the bulk of biomaterials development was to reduce to a minimum the biological response to the foreign body. This engineering design principle is still valid, 40 years later, especially for older patients, >70 years of age with approximately 10–15 years of remaining lifespan. Tens of millions of individuals have had their quality of life enhanced for up to 25 years or more by use of implants using bio-inert
biomaterials. The interface between tissues and bio-inert biomaterials is a thin, acellular fibrous capsule with minimal, if any, adhesion between the implant and its host tissue.
By 1984 the field of biomaterials had begun a shift in emphasis from achieving exclusively a bio-inert tissue response.² A second generation of biomaterials had been developed to be bioactive. Bioactive materials elicit a controlled action and reaction in the physiological environment. The mechanism of bonding of bioactive glasses (composed of Na2O-CaO-P2O5-SiO2) to living tissue, established in 1971,³ involves 11 reaction steps.⁴ The first 5 steps occur on the surface of the material (called 45S5 Bioglass). The reactions begin by rapid ion exchange of Na+ with H+ and H3O+. The ion exchange is followed by a polycondensation reaction of surface silanols (Si-OH) to create very high surface area silica (SiO2) gel, which provides a large number of sites for heterogeneous nucleation and crystallization of a biologically reactive hydroxyl-carbonate apatite (HCA) layer equivalent to the inorganic mineral phase of bone. The growing HCA layer on the surface of the material is an ideal environment for 6 cellular reaction stages. The cellular mechanisms include colonization by osteoblast stem cells (Stage 8) followed by proliferation (Stage 9) and differentiation (Stages 10,11) of the cells to form new bone that have a mechanically strong bond to the implant surface.
By the mid 1980’s bioactive materials had reached clinical use in numerous orthopaedic and dental applications.⁴ Synthetic hydroxyapatite (HA) ceramics had begun to be routinely used as porous implants, powders and coatings on metallic prostheses to provide bioactive fixation.⁵,⁶ Presence of sparingly soluble HA coatings led to a tissue response (termed osteoconduction) where bone grew along the coating and formed a mechanically strong interface.⁵,⁶ Bioactive glasses and glass-ceramics, based upon the original 45S5 Bioglass® formulation³ were being used as middle ear prostheses to restore the ossicular chain and treat conductive hearing loss and as endosseous ridge maintenance implants to preserve the alveolar ridge from the bone resorption that follows tooth extraction.⁷ The mechanically strong and tough bioactive A/W glass-ceramic, developed at Kyoto University, was used for replacement of vertebrae in patients with spinal tumours.⁸ In 1998 a centennial feature article of the American Ceramic Society documented the rapid growth of clinical use of first and second generation bioceramics.⁶
CHALLENGE NUMBER 1
Regeneration of Tissues
The clinical success of bio-inert, bioactive and resorbable implants has been a vital response to the medical needs of a rapidly aging population. However, survivability analyses of most prostheses ⁷,⁹ show that a third to half of medical devices fail within 15–25 years. Failures require patients to have revision surgery that is costly to the patients and to society and comprises a significant contribution to the rapidly rising costs of healthcare. Thirty years of research has had relatively small effects on failure rates.⁷ Continuing this approach to healthcare, based upon trial and error experiments that require use of many animals and large numbers of human clinical trials, needs to be replaced with a more affordable and more reliable alternative for the younger, 40–70 years old, patients. Improvements of either first or second generation biomaterials are limited in part because All man-made biomaterials used for repair or restoration of the body represents a compromise
.¹,⁴ It is essential to recognize that no man-made material can respond to changing physiological loads or biochemical stimuli, as do living tissues. This compromise limits the lifetime of all man-made body parts. Recognizing this fundamental limitation also signals that we have reached a limit to current medical practice that emphasises replacement of tissues. For the 21st century it is critical to emphasize a more biologically based method of repair-regeneration of tissues. Third generation bioactive materials with controlled release of biochemical stimuli provide the starting point for this shift towards a more biologically based approach to repair of diseased or damaged tissues.¹⁰
Third Generation Biomaterials: Genetic Control of Tissue Regeneration
Third generation biomaterials are being designed to stimulate specific cellular responses at the level of molecular biology.¹⁰ During the first decade of the 21st century the concepts of bioactive materials and resorbable materials converged; third generation bioactive glasses and hierarchical porous foams are being designed to activate genes that stimulate regeneration of living tissues. A design principle of such third generation materials is to control the rate of release of specific ionic stimuli that activate or regulate the function of genes in progenitor cells. Two alternative routes of repair use the new molecularly tailored third generation biomaterials.
Tissue Engineering (TE)
Progenitor cells are seeded on to molecularly modified resorbable scaffolds outside the body where the cells grow and become differentiated and mimic naturally occurring tissues. These tissue engineered constructs are then implanted into the patients to replace diseased or damaged tissues. With time the scaffolds are resorbed and replaced by host tissues that ideally include a viable blood supply and nerves. The goal is living tissue engineering constructs that can adapt to the physiological environment and provide repair or replacement that will last as long as the patient. The current status of clinical use of tissue constructs and the companies developing TE products is reviewed in reference.¹¹ Extensive clinical use is still years away, however, and regulatory and economic issues may limit many applications for many years to come.¹²
In Situ Tissue Regeneration
This approach involves the use of biomaterials in the form of powders, solutions, or doped micro- or nano-particles to stimulate local tissue repair.¹² Certain formulations of bioactive materials release chemicals in the form of ionic dissolution products at controlled rates that activate the cells in contact with the stimuli. The cells produce additional growth factors that in turn stimulate multiple generations of growing cells to self-assemble into the required tissues in situ, along the biochemical and biomechanical gradients that are present.
The advantage offered by both approaches to regenerative medicine is genetic control of the tissue repair process. The result is equivalent to repaired natural tissue in that the new structure is living and adaptable to the physiological environment.
There is growing evidence to support the hypothesis governing design of third generation biomaterials; i.e., generation of specific cell responses to controlled release of biochemical stimuli. For example, when a particulate of bioactive glass is used to fill a bone defect there is rapid regeneration of bone that matches the architecture and mechanical properties of bone in the site of repair. Both osteoconduction and osteoproduction¹³ occur as a consequence of rapid reactions on a bioactive glass surface.⁴ The surface reactions release critical concentrations of soluble Si, Ca, P and Na ions that give rise to both intracellular and extracellular responses at the interface of the glass with its cellular environment. Attachment and synchronised proliferation and differentiation of osteoblasts rapidly occurs on the surface of bioactive materials.¹⁴ Osteoprogenitor cells capable of forming new bone colonise the surface of highly bioactive materials. Slow release of soluble ions from the material stimulates cell division and production of growth factors and extracellular matrix proteins. Mineralisation of the matrix follows and the mature osteoblast phenotype, encased in a collagen-HCA matrix (osteocytes) is the final product both in vitro and in vivo.¹³-²²
Research has established that there is genetic control of the cellular response to the most reactive of the bioactive glasses (45S5 Bioglass). Seven families of genes are up-regulated when primary human osteoblasts are exposed to the ionic dissolution products of bioactive glasses.¹⁷,²³ The gene expression occurs within 48 hours, and includes enhanced expression by more than