Special Issue "Biomaterials for Bone Substitutes"

Guest Editor
Prof. Dr. Rodolfo Quarto
Centro Biotecnologie Avanzate, Genova, Italy, Department of Experimental Medicine Università di Genova, Italy
Website: http://www.unige.it/staff/persone/rdn/FBoAVFtHAQINGAYUHQUYGgAYfEEcEVQdBVNVXxhJBUN8JDksLDVNFwdUBwU=
E-Mail: rodolfo.quarto@unige.it
Interests: bone stem cells; biomaterials; tissue engineering; bioreactors

Dear Colleagues,

Biomaterial science holds the promise to solve several problems related to tissue and organ replacement. Several approaches in regenerative medicine, of which tissue engineering is an important part, involve stem cells loaded onto properly designed biomaterials, with the aim of inducing cell differentiation along a pre-defined pathway and regenerating the target tissue according to physiological cues. In clinical practice bone regeneration is a particular challenge, as the demand is increasing due to an ageing population and a high prevalence of osteoporosis. In addition, weight-bearing issues also require consideration in bone biomaterial applications.  One of the most intriguing concepts is to design materials able to mimic specific microenvironments, possibly priming the natural processes of cell-driven tissue regeneration. The ideal scaffold should therefore transmit molecular signals at the right time and in the right dose. Scaffold chemical composition thus becomes of crucial importance, but other essential parameters of the scaffold design have to be considered, since they may profoundly influence cell fate both in vitro and in vivo. Indeed, to improve the efficiency of biomaterials aimed at tissue regeneration, the design of the overall architecture of the scaffold, including macro-, micro- and nanostructure, takes on major significance and remains a multi-disciplinary challenge.

Prof. Dr. C. James Kirkpatrick,
Prof. Dr. Rodolfo Quarto
Guest Editors

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• functional biomaterials
• scaffolds
• microenvironment
• biomimetic cues
• stem cells
• bone regeneration

Title: Bioactive Polymeric Composites for Tooth Mineral Regeneration: Physicochemical and Cellular Aspects
Authors: D. Skrtic ¹ and J.M. Antonucci ²
Affiliations: ¹ Paffenbarger Research Center, American Dental Association Foundation
² Polymers Division, National Institute of Standards and Technology; Gaithersburg, MD 20899, USA
Abstract: Our studies of amorphous calcium phosphate (ACP)-based dental materials are focused on the design of bioactive, non-degradable, biocompatible, polymeric composites derived from acrylic monomer systems and ACP by photochemical polymerization. Their intended uses include remineralizing bases/liners, orthodontic adhesives and/or endodontic sealers. The bioactivity of these materials originates from the propensity of ACP, once exposed to oral fluids, to release Ca and PO4 ions (building blocks of tooth and bone mineral) in sustained manner while spontaneously converting to thermodynamically stable apatite. As a result of ACP's bioactivity, local Ca- and PO4-enriched environments are created with supersaturation conditions favorable for the regeneration of tooth mineral lost to decay or wear.  Besides its applicative purpose, our research also seeks to expand the fundamental knowledge base of structure-composition-property relationships existing in these complex systems and identify the mechanisms that govern filler/polymer and composite/tooth interfacial phenomena. In addition to the extensive physicochemical evaluation, we also assess the leachability of the unreacted monomers and in vitro cellular responses to these types of dental materials. The systematic physicochemical and cellular assessments presented in this study typically provide model materials suitable for further animal and/or clinical testing. In addition to their potential dental clinical value, these studies suggest the future development of calcium phosphate-based biomaterials based on composite materials derived from a biodegradable polymers and ACP, and designed for general bone tissue regeneration.

Title: Rationale, Characteristics, and Clinical Performance of the OsteoSponge: A Novel Allograft for Treatment of Osseous Defects
Authors: Larry E. Miller.^1,2 and Jon E. Block ²
Affiliations: ¹ Miller Scientific Consulting, Inc., 422 Mountain Wasp Drive, Biltmore Lake, NC 28715 USA
² 2210 Jackson Street, Suite 401, San Francisco, CA 94115 USA; E-Mail: jonblock@jonblockphd.com
Abstract: A variety of bone grafts and bone graft substitutes, each with distinctly different characteristics, are available to the orthopaedic surgeon for various reconstructive procedures. However, adequate reconstruction of osseous defects remains a therapeutic challenge. Each bone graft option has a unique set of benefits and risks that must be considered in relation to the particular pathology in order to achieve the best possible outcome. The OsteoSpongeÒ (Bacterin International, Inc., Belgrade, MT, USA) allograft consists of 100% demineralized human cancellous bone with no additional carrier materials. The OsteoSponge is compressible, thereby allowing precise graft placement in most osseous defects, and subsequently expands to completely fill the void. The material is prepared using methods that preserve native growth factors, thereby promoting cellular ingrowth and proliferation and, ultimately, osteogenesis. This article describes the rationale for and the characteristics of the OsteoSponge and summarizes results from preclinical and human studies with this novel allograft material.
Keywords: allograft; bone graft; osseous defect; OsteoSponge

Title: Anabolic Actions of the Regenerative Agent Enamel Matrix Derivative (EMD) in Oral Periosteal Fibroblasts and MG 63 Osteoblasts; Modulation by Nicotine and Glutathione in a Redox Environment
Authors: Tareq Al-Qattan and Mena Soory
Affiliation: Periodontology, King’s College London Dental Institute, UK; E-Mail: mena.soory@kcl.ac.uk
Abstract: Our study seeks to explore anabolic effects of a periodontal regenerative agent enamel matrix derivative (EMD) used in bone defects and its modulation by nicotine and the anti-oxidant glutathione (GSH),  in a cell culture model comprising  human periosteal fibroblasts (HPF) and MG63 osteoblasts. Androgen biomarkers of oxidative stress and healing, resulting from radiolabelled androgen substrates are assayed. This in vitro model simulates a redox environment relevant to the periodontal lesion with applications for regenerative procedures using EMD; and modulation of redox status in response to environmental factors. Monolayer cultures of MG63 osteoblasts and HPF established in Eagle's MEM are incubated with androgen substrates, and optimal concentrations of EMD, nicotine and GSH, alone and in combination. EMD  significantly enhances yields of 5α-dihydrotestosterone (DHT) an effective bioactive metabolite, alone and in combination with GSH, to overcome oxidative effects of nicotine across cultures (n=8; p<0.0001). The ‘in vitro’ findings of this study could be extrapolated to ‘in vivo’ applications of EMD as an adjunctive regenerative therapeutic agent in an environment of chronic inflammation and oxidative stress. Increased yields of DHT implicated in matrix synthesis and direct antioxidant capacity, confirm the potential applications for enamel matrix derivative in bone regenerative procedures.
Keywords: enamel matrix derivative; redox status; antioxidant; regeneration

Title: Toughening of Porous Si-substituted Tri-calcium Phosphate Scaffolds with Polymer Coatings
Authors: S.V. Dorozhkin ¹, T. Ajaal ¹, R.W. Smith ¹ and T.J.N. Smith ²
Affiliations: ¹ Department of Mechanical and Materials Engineering, Queen’s University, Nicol Hall, Kingston, Ontario, Canada K7L 3N6; E-Mail: smithrw@queensu.ca
² Octane Medical Group, 640 Cataraqui Woods Drive, Kingston, Ontario Canada K7P 2Y5
Abstract: The calcium phosphate scaffolds currently used as bone substitutes are naturally brittle and so not ‘user-friendly’ in a clinical setting – i.e. the use of conventional shaping tools leads to much granulation. Whilst this may not be a serious problem in (say) packing a bone cavity, if the scaffold carries a bone growth factor, a migrating bone substitute fragment might cause later problems. In an attempt to provide greater surgical ‘user-friendliness’ and ensure all substitute bone fragments stay at the insertion site, the mechanical properties of polymer-coated scaffold implants were investigated. In order to arrive at a robust method of preparation to maximize mechanical advantage and minimise preparation costs, a statistical experimental design and the Taguchi optimization method were used. Tri-calcium phosphate was used for the scaffold and polycaprolactone as the biodegradable polymer.  Flexural strength and the amount of deposited polymer in the samples were considered the measured responses for this study. Using the optimum experimental conditions for preparing samples, high quality scaffold implants with 19.1 MPa flexural strength and 0.4 gm of total mass (with dimensions of 8.5 mm in diameter and 13 mm wide) can be prepared, which meet the intended design characteristics.
Keywords: Tri-calcium Phosphates; Polycaprolactone; Toughening; Porous Scaffolds; Mechanical Properties