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Novel Advances and Approaches in Biomedical Materials Based on Calcium Phosphates

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A special issue of Materials (ISSN 1996-1944).

Deadline for manuscript submissions: closed (31 August 2018) | Viewed by 54565

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Dr. Michael R. Mucalo

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Associate Professor, School of Science, University of Waikato, Hamilton, New Zealand
Interests: biomedical materials; calcium phosphate chemistry; metal colloids; IR spectroelectrochemistry; repurposing of byproducts/waste; application of IR spectroscopy, solid state NMR; drug delivery
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Dear Colleagues,

Research into the use of calcium phosphates in the development and clinical application of biomedical materials has been a significantly diverse activity by a wide range of scientists, engineers and medical practitioners, among others. The field of research in this area can hence be truly defined as interdisciplinary and much interesting work leading to imaginative and innovative solutions for the improvement of health outcomes continues.

It is the intention of this Special Issue to summarize a wide selection of the current advances in this area. We thus invite contributions to this issue in the form of original articles, review articles, research notes and short communications from various areas of this scientific discipline. Areas of interest that could be covered are contributions based on uses of natural by products to form potential biomaterials, novel composites of calcium phosphates with other materials, chemical manipulations of calcium phosphates that lead to novel biomaterials, studies advancing further the cell biology surrounding the incorporation of calcium phosphate biomaterials, engineering/biomechanical aspects of using calcium phosphate biomaterials and human or animal clinical studies involving calcium phosphates. Studies on novel approaches to characterization to study these materials would also be of interest. Other types of contribution welcomed would be from those involved with regulating the use of calcium phosphate biomaterials. Hence, we invite, scientists, engineers, doctors, and medical device regulators to submit articles of interest.

It is hoped that this Special Issue will be enriched with these very diverse topics that provide an overall picture of advancements in this area.

We look forward to your contributions. Each article will be subject to rigorous peer review.

Associate Professor Michael R. Mucalo

Guest Editor

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Keywords

calcium phosphate
hydroxyapatite
characterisation
regulation
natural matrices
clinical use
orthopedics
xenografts
medical devices

Published Papers (10 papers)

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Editorial

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6 pages, 181 KiB

Open AccessEditorial

Special Issue: Novel Advances and Approaches in Biomedical Materials Based on Calcium Phosphates

by Michael R. Mucalo

Materials 2019, 12(3), 405; https://doi.org/10.3390/ma12030405 - 28 Jan 2019

Cited by 10 | Viewed by 2677

Abstract

Research on calcium phosphate use in the development and clinical application of biomedical materials is a diverse activity and is genuinely interdisciplinary, with much work leading to innovative solutions for improvement of health outcomes. This Special Issue aimed to summarize current advances in this area. The nine papers published cover a wide spectrum of topical areas, such as (1) remineralisation pastes for decalcified teeth, (2) use of statins to enhance bone formation, (3) how dolomitic marble and seashells can be processed into bioceramic materials, (4) relationships between the roughness of calcium phosphate surfaces and surface charge with the effect on human MRC osteogenic differentiation and maturation being investigated, (5) rheological and mechanical properties of a novel injectable bone substitute, (6) improving strength of bone cements by incorporating reinforcing chemically modified fibres, (7) using adipose stem cells to stimulate osteogenesis, osteoinduction, and angiogenesis on calcium phosphates, (8) using glow discharge treatments to remove surface contaminants from biomedical materials to enhance cell attachment and improve bone generation, and (9) a review on how classically brittle hydroxyapatite based scaffolds can be improved by making fibre-hydroxyapatite composites, with detailed analysis of ceramic crack propagation mechanisms and its prevention via fibre incorporation in the hydroxyapatite. Full article

(This article belongs to the Special Issue Novel Advances and Approaches in Biomedical Materials Based on Calcium Phosphates)

Research

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10 pages, 3739 KiB

Open AccessArticle

A Novel Fluoride Containing Bioactive Glass Paste is Capable of Re-Mineralizing Early Caries Lesions

by Ahmed Samir Bakry, Mona Aly Abbassy, Hanin Fahad Alharkan, Sara Basuhail, Khalil Al-Ghamdi and Robert Hill

Materials 2018, 11(9), 1636; https://doi.org/10.3390/ma11091636 - 06 Sep 2018

Cited by 43 | Viewed by 6062

Abstract

White-spot-lesions (WSL) are a common complication associated with orthodontic treatment. In the current study, the remineralization efficacy of a BiominF^® paste was compared to the efficacy of a fluoride gel. Methods: Orthodontic brackets were bonded to 60 human premolars buccal surfaces, which were covered with varnish, except a small treatment area (3 mm²). All specimens were challenged by a demineralization solution for 4 days. Specimens were assigned into 4 groups: BiominF^® paste, Fluoride (4-min application), fluoride (twenty four hours application), and the control (n = 15). After cross-sectioning, enamel slabs having a thickness of approximately 100–120 μm were obtained. A TMR (Transverse Micro Radiography) technique was used to observe the sub-surface enamel lesions’ depth and mineral density, and their response to the remineralization protocols. One way ANOVA was used to analyze the results (α = 0.05). The top and the cross-sectional surfaces were observed using SEM/EDS. Results: Specimens treated with BiominF^® paste showed significant decrease in delta z values, however lesion depth showed no significant difference when compared to the other three groups (p < 0.05). SEM/EDS observation showed the formation of crystal like structures on top of enamel demineralized surfaces, when treated with BiominF^® paste. In conclusion BiominF^® paste can be considered an effective remineralizing agent for white spot Lesions. Full article

(This article belongs to the Special Issue Novel Advances and Approaches in Biomedical Materials Based on Calcium Phosphates)

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15 pages, 4660 KiB

Open AccessArticle

Carbonate Apatite Containing Statin Enhances Bone Formation in Healing Incisal Extraction Sockets in Rats

by Yunia Dwi Rakhmatia, Yasunori Ayukawa, Akihiro Furuhashi and Kiyoshi Koyano

Materials 2018, 11(7), 1201; https://doi.org/10.3390/ma11071201 - 12 Jul 2018

Cited by 12 | Viewed by 3500

Abstract

The purpose of this study was to evaluate the feasibility of using apatite blocks fabricated by a dissolution–precipitation reaction of preset gypsum, with or without statin, to enhance bone formation during socket healing after tooth extraction. Preset gypsum blocks were immersed in a Na₃PO₄ aqueous solution to make hydroxyapatite (HA) low crystalline and HA containing statin (HAFS), or in a mixed solution of Na₂HPO₄ and NaHCO₃ to make carbonate apatite (CO) and CO containing statin (COFS). The right mandibular incisors of four-week-old male Wistar rats were extracted and the sockets were filled with one of the bone substitutes or left untreated as a control (C). The animals were sacrificed at two and four weeks. Areas in the healing socket were evaluated by micro-computed tomography (micro-CT) and histological analyses. The bone volume, trabecular thickness, and trabecular separation were greatest in the COFS group, followed by the CO, HAFS, HA, and C groups. The bone mineral density of the COFS group was greater than that of the other groups when evaluated in the vertical plane. The results of this study suggest that COFS not only allowed, but also promoted, bone healing in the socket. This finding could be applicable for alveolar bone preservation after tooth extraction. Full article

(This article belongs to the Special Issue Novel Advances and Approaches in Biomedical Materials Based on Calcium Phosphates)

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15 pages, 4731 KiB

Open AccessArticle

Osteoblast Cell Response to Naturally Derived Calcium Phosphate-Based Materials

by Valentina Mitran, Raluca Ion, Florin Miculescu, Madalina Georgiana Necula, Aura-Catalina Mocanu, George E. Stan, Iulian Vasile Antoniac and Anisoara Cimpean

Materials 2018, 11(7), 1097; https://doi.org/10.3390/ma11071097 - 27 Jun 2018

Cited by 25 | Viewed by 4088

Abstract

The demand of calcium phosphate bioceramics for biomedical applications is constantly increasing. Efficient and cost-effective production can be achieved using naturally derived materials. In this work, calcium phosphate powders, obtained from dolomitic marble and Mytilus galloprovincialis seashells by a previously reported and improved Rathje method were used to fabricate microporous pellets through cold isostatic pressing followed by sintering at 1200 °C. The interaction of the developed materials with MC3T3-E1 pre-osteoblasts was explored in terms of cell adhesion, morphology, viability, proliferation, and differentiation to evaluate their potential for bone regeneration. Results showed appropriate cell adhesion and high viability without distinguishable differences in the morphological features. Likewise, the pre-osteoblast proliferation overtime on both naturally derived calcium phosphate materials showed a statistically significant increase comparable to that of commercial hydroxyapatite, used as reference material. Furthermore, evaluation of the intracellular alkaline phosphatase activity and collagen synthesis and deposition, used as markers of the osteogenic ability of these bioceramics, revealed that all samples promoted pre-osteoblast differentiation. However, a seashell-derived ceramic demonstrated a higher efficacy in inducing cell differentiation, almost equivalent to that of the commercial hydroxyapatite. Therefore, data obtained demonstrate that this naturally sourced calcium-phosphate material holds promise for applications in bone tissue regeneration. Full article

(This article belongs to the Special Issue Novel Advances and Approaches in Biomedical Materials Based on Calcium Phosphates)

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25 pages, 5233 KiB

Open AccessArticle

Nanoscale Electrical Potential and Roughness of a Calcium Phosphate Surface Promotes the Osteogenic Phenotype of Stromal Cells

by Igor A. Khlusov, Yuri Dekhtyar, Yurii P. Sharkeev, Vladimir F. Pichugin, Marina Y. Khlusova, Nataliya Polyaka, Fedor Tyulkin, Viktorija Vendinya, Elena V. Legostaeva, Larisa S. Litvinova, Valeria V. Shupletsova, Olga G. Khaziakhmatova, Kristina A. Yurova and Konstantin A. Prosolov

Materials 2018, 11(6), 978; https://doi.org/10.3390/ma11060978 - 09 Jun 2018

Cited by 30 | Viewed by 4060

Abstract

Mesenchymal stem cells (MSCs) and osteoblasts respond to the surface electrical charge and topography of biomaterials. This work focuses on the connection between the roughness of calcium phosphate (CP) surfaces and their electrical potential (EP) at the micro- and nanoscales and the possible role of these parameters in jointly affecting human MSC osteogenic differentiation and maturation in vitro. A microarc CP coating was deposited on titanium substrates and characterized at the micro- and nanoscale. Human adult adipose-derived MSCs (hAMSCs) or prenatal stromal cells from the human lung (HLPSCs) were cultured on the CP surface to estimate MSC behavior. The roughness, nonuniform charge polarity, and EP of CP microarc coatings on a titanium substrate were shown to affect the osteogenic differentiation and maturation of hAMSCs and HLPSCs in vitro. The surface EP induced by the negative charge increased with increasing surface roughness at the microscale. The surface relief at the nanoscale had an impact on the sign of the EP. Negative electrical charges were mainly located within the micro- and nanosockets of the coating surface, whereas positive charges were detected predominantly at the nanorelief peaks. HLPSCs located in the sockets of the CP surface expressed the osteoblastic markers osteocalcin and alkaline phosphatase. The CP multilevel topography induced charge polarity and an EP and overall promoted the osteoblast phenotype of HLPSCs. The negative sign of the EP and its magnitude at the micro- and nanosockets might be sensitive factors that can trigger osteoblastic differentiation and maturation of human stromal cells. Full article

(This article belongs to the Special Issue Novel Advances and Approaches in Biomedical Materials Based on Calcium Phosphates)

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17 pages, 17288 KiB

Open AccessArticle

Rheological and Mechanical Properties of Thermoresponsive Methylcellulose/Calcium Phosphate-Based Injectable Bone Substitutes

by Öznur Demir Oğuz and Duygu Ege

Materials 2018, 11(4), 604; https://doi.org/10.3390/ma11040604 - 14 Apr 2018

Cited by 29 | Viewed by 6020

Abstract

In this study, a novel injectable bone substitute (IBS) was prepared by incorporating a bioceramic powder in a polymeric solution comprising of methylcellulose (MC), gelatin and citric acid. Methylcellulose was utilized as the polymeric matrix due to its thermoresponsive properties and biocompatibility. 2.5 wt % gelatin and 3 wt % citric acid were added to the MC to adjust the rheological properties of the prepared IBS. Then, 0, 20, 30 and 50 wt % of the bioceramic component comprising tetracalcium phosphate/hydroxyapatite (TTCP/HA), dicalcium phosphate dehydrate (DCPD) and calcium sulfate dehydrate (CSD) were added into the prepared polymeric component. The prepared IBS samples had a chewing gum-like consistency. IBS samples were investigated in terms of their chemical structure, rheological characteristics, and mechanical properties. After that, in vitro degradation studies were carried out by measurement of pH and % remaining weight. Viscoelastic characteristics of the samples indicated that all of the prepared IBS were injectable and they hardened at approximately 37 °C. Moreover, with increasing wt % of the bioceramic component, the degradation rate of the samples significantly reduced and the mechanical properties were improved. Therefore, the experimental results indicated that the P50 mix may be a promising candidates to fill bone defects and assist bone recovery for non-load bearing applications. Full article

(This article belongs to the Special Issue Novel Advances and Approaches in Biomedical Materials Based on Calcium Phosphates)

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12 pages, 5145 KiB

Open AccessFeature PaperArticle

The Mechanical Properties of Biocompatible Apatite Bone Cement Reinforced with Chemically Activated Carbon Fibers

by Anne V. Boehm, Susanne Meininger, Annemarie Tesch, Uwe Gbureck and Frank A. Müller

Materials 2018, 11(2), 192; https://doi.org/10.3390/ma11020192 - 26 Jan 2018

Cited by 30 | Viewed by 5078

Abstract

Calcium phosphate cement (CPC) is a well-established bone replacement material in dentistry and orthopedics. CPC mimics the physicochemical properties of natural bone and therefore shows excellent in vivo behavior. However, due to their brittleness, the application of CPC implants is limited to non-load bearing areas. Generally, the fiber-reinforcement of ceramic materials enhances fracture resistance, but simultaneously reduces the strength of the composite. Combining strong C-fiber reinforcement with a hydroxyapatite to form a CPC with a chemical modification of the fiber surface allowed us to adjust the fiber–matrix interface and consequently the fracture behavior. Thus, we could demonstrate enhanced mechanical properties of CPC in terms of bending strength and work of fracture to a strain of 5% (WOF5). Hereby, the strength increased by a factor of four from 9.2 ± 1.7 to 38.4 ± 1.7 MPa. Simultaneously, the WOF5 increased from 0.02 ± 0.004 to 2.0 ± 0.6 kJ∙m⁻², when utilizing an aqua regia/CaCl₂ pretreatment. The cell proliferation and activity of MG63 osteoblast-like cells as biocompatibility markers were not affected by fiber addition nor by fiber treatment. CPC reinforced with chemically activated C-fibers is a promising bone replacement material for load-bearing applications. Full article

(This article belongs to the Special Issue Novel Advances and Approaches in Biomedical Materials Based on Calcium Phosphates)

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16 pages, 2946 KiB

Open AccessArticle

Blood Vessel Formation and Bone Regeneration Potential of the Stromal Vascular Fraction Seeded on a Calcium Phosphate Scaffold in the Human Maxillary Sinus Floor Elevation Model

by Elisabet Farré-Guasch, Nathalie Bravenboer, Marco N. Helder, Engelbert A. J. M. Schulten, Christiaan M. Ten Bruggenkate and Jenneke Klein-Nulend

Materials 2018, 11(1), 161; https://doi.org/10.3390/ma11010161 - 20 Jan 2018

Cited by 45 | Viewed by 6276

Abstract

Bone substitutes are used as alternatives for autologous bone grafts in patients undergoing maxillary sinus floor elevation (MSFE) for dental implant placement. However, bone substitutes lack osteoinductive and angiogenic potential. Addition of adipose stem cells (ASCs) may stimulate osteogenesis and osteoinduction, as well as angiogenesis. We aimed to evaluate the vascularization in relation to bone formation potential of the ASC-containing stromal vascular fraction (SVF) of adipose tissue, seeded on two types of calcium phosphate carriers, within the human MSFE model, in a phase I study. Autologous SVF was obtained from ten patients and seeded on β-tricalcium phosphate (n = 5) or biphasic calcium phosphate carriers (n = 5), and used for MSFE in a one-step surgical procedure. After six months, biopsies were obtained during dental implant placement, and the quantification of the number of blood vessels was performed using histomorphometric analysis and immunohistochemical stainings for blood vessel markers, i.e., CD34 and alpha-smooth muscle actin. Bone percentages seemed to correlate with blood vessel formation and were higher in study versus control biopsies in the cranial area, in particular in β-tricalcium phosphate-treated patients. This study shows the safety, feasibility, and efficiency of the use of ASCs in the human MSFE, and indicates a pro-angiogenic effect of SVF. Full article

(This article belongs to the Special Issue Novel Advances and Approaches in Biomedical Materials Based on Calcium Phosphates)

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4206 KiB

Open AccessArticle

Enhancement of Osteoblastic-Like Cell Activity by Glow Discharge Plasma Surface Modified Hydroxyapatite/β-Tricalcium Phosphate Bone Substitute

by Eisner Salamanca, Yu-Hwa Pan, Aileen I. Tsai, Pei-Ying Lin, Ching-Kai Lin, Haw-Ming Huang, Nai-Chia Teng, Peter D. Wang and Wei-Jen Chang

Materials 2017, 10(12), 1347; https://doi.org/10.3390/ma10121347 - 23 Nov 2017

Cited by 15 | Viewed by 4116

Abstract

Glow discharge plasma (GDP) treatments of biomaterials, such as hydroxyapatite/β-tricalcium phosphate (HA/β-TCP) composites, produce surfaces with fewer contaminants and may facilitate cell attachment and enhance bone regeneration. Thus, in this study we used argon glow discharge plasma (Ar-GDP) treatments to modify HA/β-TCP particle surfaces and investigated the physical and chemical properties of the resulting particles (HA/β-TCP + Ar-GDP). The HA/β-TCP particles were treated with GDP for 15 min in argon gas at room temperature under the following conditions: power: 80 W; frequency: 13.56 MHz; pressure: 100 mTorr. Scanning electron microscope (SEM) observations showed similar rough surfaces of HA/β-TCP + Ar-GDP HA/β-TCP particles, and energy dispersive spectrometry analyses showed that HA/β-TCP surfaces had more contaminants than HA/β-TCP + Ar-GDP surfaces. Ca/P mole ratios in HA/β-TCP and HA/β-TCP + Ar-GDP were 1.34 and 1.58, respectively. Both biomaterials presented maximal intensities of X-ray diffraction patterns at 27° with 600 a.u. At 25° and 40°, HA/β-TCP + Ar-GDP and HA/β-TCP particles had peaks of 200 a.u., which are similar to XRD intensities of human bone. In subsequent comparisons, MG-63 cell viability and differentiation into osteoblast-like cells were assessed on HA/β-TCP and HA/β-TCP + Ar-GDP surfaces, and Ar-GDP treatments led to improved cell growth and alkaline phosphatase activities. The present data indicate that GDP surface treatment modified HA/β-TCP surfaces by eliminating contaminants, and the resulting graft material enhanced bone regeneration. Full article

(This article belongs to the Special Issue Novel Advances and Approaches in Biomedical Materials Based on Calcium Phosphates)

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Review

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32 pages, 5061 KiB

Open AccessReview

A Review on the Use of Hydroxyapatite-Carbonaceous Structure Composites in Bone Replacement Materials for Strengthening Purposes

by Humair A. Siddiqui, Kim L. Pickering and Michael R. Mucalo

Materials 2018, 11(10), 1813; https://doi.org/10.3390/ma11101813 - 24 Sep 2018

Cited by 109 | Viewed by 11761

Abstract

Biomedical materials constitute a vast scientific research field, which is devoted to producing medical devices which aid in enhancing human life. In this field, there is an enormous demand for long-lasting implants and bone substitutes that avoid rejection issues whilst providing favourable bioactivity, osteoconductivity and robust mechanical properties. Hydroxyapatite (HAp)-based biomaterials possess a close chemical resemblance to the mineral phase of bone, which give rise to their excellent biocompatibility, so allowing for them to serve the purpose of a bone-substituting and osteoconductive scaffold. The biodegradability of HAp is low (Ksp ≈ 6.62 × 10⁻¹²⁶) as compared to other calcium phosphates materials, however they are known for their ability to develop bone-like apatite coatings on their surface for enhanced bone bonding. Despite its favourable bone regeneration properties, restrictions on the use of pure HAp ceramics in high load-bearing applications exist due to its inherently low mechanical properties (including low strength and fracture toughness, and poor wear resistance). Recent innovations in the field of bio-composites and nanoscience have reignited the investigation of utilising different carbonaceous materials for enhancing the mechanical properties of composites, including HAp-based bio-composites. Researchers have preferred carbonaceous materials with hydroxyapatite due to their inherent biocompatibility and good structural properties. It has been demonstrated that different structures of carbonaceous material can be used to improve the fracture toughness of HAp, as they can easily serve the purpose of being a second phase reinforcement, with the resulting composite still being a biocompatible material. Nanostructured carbonaceous structures, especially those in the form of fibres and sheets, were found to be very effective in increasing the fracture toughness values of HAp. Minor addition of CNTs (3 wt.%) has resulted in a more than 200% increase in fracture toughness of hydroxyapatite-nanorods/CNTs made using spark plasma sintering. This paper presents a current review of the research field of using different carbonaceous materials composited with hydroxyapatite with the intent being to produce high performance biomedically targeted materials. Full article

(This article belongs to the Special Issue Novel Advances and Approaches in Biomedical Materials Based on Calcium Phosphates)

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