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23 pages, 7866 KiB

Open AccessArticle

Novel Biocement/Honey Composites for Bone Regenerative Medicine

by Lubomir Medvecky, Maria Giretova, Radoslava Stulajterova, Tibor Sopcak, Pavlina Jevinova and Lenka Luptakova

J. Funct. Biomater. 2023, 14(9), 457; https://doi.org/10.3390/jfb14090457 - 04 Sep 2023

Viewed by 1184

Abstract

New biocements based on a powdered mixture of calcium phosphate/monetite (TTCPM) modified with the addition of honey were prepared by mixing the powder and honey liquid components at a non-cytotoxic concentration of honey (up to 10% (w/v)). The setting [...] Read more.

New biocements based on a powdered mixture of calcium phosphate/monetite (TTCPM) modified with the addition of honey were prepared by mixing the powder and honey liquid components at a non-cytotoxic concentration of honey (up to 10% (w/v)). The setting process of the cements was not affected by the addition of honey, and the setting time of ~4 min corresponded to the fast setting calcium phosphate cements (CPCs). The cement powder mixture was completely transformed into calcium-deficient nanohydroxyapatite after 24 h of hardening in a simulated body fluid, and the columnar growth of long, needle-like nanohydroxyapatite particles around the original calcium phosphate particles was observed in the honey cements. The compressive strength of the honey cements was reduced with the content of honey in the cement. Comparable antibacterial activities were found for the cements with honey solutions on Escherichia coli, but very low antibacterial activities were found for Staphylococcus aureus for all the cements. The enhanced antioxidant inhibitory activity of the composite extracts was verified. In vitro cytotoxicity testing verified the non-cytotoxic nature of the honey cement extracts, and the addition of honey promoted alkaline phosphatase activity, calcium deposit production, and the upregulation of osteogenic genes (osteopontin, osteocalcin, and osteonectin) by mesenchymal stem cells, demonstrating the positive synergistic effect of honey and CPCs on the bioactivity of cements that could be promising therapeutic candidates for the repair of bone defects. Full article

(This article belongs to the Special Issue Functionalized Biomimetic Calcium Phosphates 2.0)

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22 pages, 21315 KiB

Open AccessEditor’s ChoiceArticle

Calcium Phosphate Cements Combined with Blood as a Promising Tool for the Treatment of Bone Marrow Lesions

by Maxence Limelette, Claire De Fourmestraux, Christelle Despas, Audrey Lafragette, Joelle Veziers, Yohan Le Guennec, Gwenola Touzot-Jourde, François-Xavier Lefevre, Elise Verron, Jean-Michel Bouler, Bruno Bujoli and Olivier Gauthier

J. Funct. Biomater. 2023, 14(4), 204; https://doi.org/10.3390/jfb14040204 - 07 Apr 2023

Viewed by 1346

Abstract

The solid phase of a commercial calcium phosphate (Graftys^® HBS) was combined with ovine or human blood stabilized either with sodium citrate or sodium heparin. The presence of blood delayed the setting reaction of the cement by ca. 7–15 h, depending on [...] Read more.

The solid phase of a commercial calcium phosphate (Graftys^® HBS) was combined with ovine or human blood stabilized either with sodium citrate or sodium heparin. The presence of blood delayed the setting reaction of the cement by ca. 7–15 h, depending on the nature of the blood and blood stabilizer. This phenomenon was found to be directly related to the particle size of the HBS solid phase, since prolonged grinding of the latter resulted in a shortened setting time (10–30 min). Even though ca. 10 h were necessary for the HBS blood composite to harden, its cohesion right after injection was improved when compared to the HBS reference as well as its injectability. A fibrin-based material was gradually formed in the HBS blood composite to end-up, after ca. 100 h, with a dense 3D organic network present in the intergranular space, thus affecting the microstructure of the composite. Indeed, SEM analyses of polished cross-sections showed areas of low mineral density (over 10–20 µm) spread in the whole volume of the HBS blood composite. Most importantly, when the two cement formulations were injected in the tibial subchondral cancellous bone in a bone marrow lesion ovine model, quantitative SEM analyses showed a highly significant difference between the HBS reference versus its analogue combined with blood. After a 4-month implantation, histological analyses clearly showed that the HBS blood composite underwent high resorption (remaining cement: ca. 13.1 ± 7.3%) and new bone formation (newly formed bone: 41.8 ± 14.7%). This was in sharp contrast with the case of the HBS reference for which a low resorption rate was observed (remaining cement: 79.0 ± 6.9%; newly formed bone: 8.6 ± 4.8%). This study suggested that the particular microstructure, induced by the use of blood as the HBS liquid phase, favored quicker colonization of the implant and acceleration of its replacement by newly formed bone. For this reason, the HBS blood composite might be worth considering as a potentially suitable material for subchondroplasty. Full article

(This article belongs to the Special Issue Functionalized Biomimetic Calcium Phosphates 2.0)

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17 pages, 2373 KiB

Open AccessArticle

Inhalable Microparticles Embedding Biocompatible Magnetic Iron-Doped Hydroxyapatite Nanoparticles

by Eride Quarta, Michele Chiappi, Alessio Adamiano, Anna Tampieri, Weijie Wang, Teresa D. Tetley, Francesca Buttini, Fabio Sonvico, Daniele Catalucci, Paolo Colombo, Michele Iafisco and Lorenzo Degli Esposti

J. Funct. Biomater. 2023, 14(4), 189; https://doi.org/10.3390/jfb14040189 - 28 Mar 2023

Cited by 3 | Viewed by 1625

Abstract

Recently, there has been increasing interest in developing biocompatible inhalable nanoparticle formulations, as they have enormous potential for treating and diagnosing lung disease. In this respect, here, we have studied superparamagnetic iron-doped calcium phosphate (in the form of hydroxyapatite) nanoparticles (FeCaP NPs) which [...] Read more.

Recently, there has been increasing interest in developing biocompatible inhalable nanoparticle formulations, as they have enormous potential for treating and diagnosing lung disease. In this respect, here, we have studied superparamagnetic iron-doped calcium phosphate (in the form of hydroxyapatite) nanoparticles (FeCaP NPs) which were previously proved to be excellent materials for magnetic resonance imaging, drug delivery and hyperthermia-related applications. We have established that FeCaP NPs are not cytotoxic towards human lung alveolar epithelial type 1 (AT1) cells even at high doses, thus proving their safety for inhalation administration. Then, D-mannitol spray-dried microparticles embedding FeCaP NPs have been formulated, obtaining respirable dry powders. These microparticles were designed to achieve the best aerodynamic particle size distribution which is a critical condition for successful inhalation and deposition. The nanoparticle-in-microparticle approach resulted in the protection of FeCaP NPs, allowing their release upon microparticle dissolution, with dimensions and surface charge close to the original values. This work demonstrates the use of spray drying to provide an inhalable dry powder platform for the lung delivery of safe FeCaP NPs for magnetically driven applications. Full article

(This article belongs to the Special Issue Functionalized Biomimetic Calcium Phosphates 2.0)

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16 pages, 12385 KiB

Open AccessEditor’s ChoiceArticle

Development of Neovasculature in Axially Vascularized Calcium Phosphate Cement Scaffolds

by Yassine Ouhaddi, Baptiste Charbonnier, Juliette Porge, Yu-Ling Zhang, Isadora Garcia, Uwe Gbureck, Liam Grover, Mirko Gilardino, Edward Harvey, Nicholas Makhoul and Jake Barralet

J. Funct. Biomater. 2023, 14(2), 105; https://doi.org/10.3390/jfb14020105 - 14 Feb 2023

Viewed by 1564

Abstract

Augmenting the vascular supply to generate new tissues, a crucial aspect in regenerative medicine, has been challenging. Recently, our group showed that calcium phosphate can induce the formation of a functional neo-angiosome without the need for microsurgical arterial anastomosis. This was a preclinical [...] Read more.

Augmenting the vascular supply to generate new tissues, a crucial aspect in regenerative medicine, has been challenging. Recently, our group showed that calcium phosphate can induce the formation of a functional neo-angiosome without the need for microsurgical arterial anastomosis. This was a preclinical proof of concept for biomaterial-induced luminal sprouting of large-diameter vessels. In this study, we investigated if sprouting was a general response to surgical injury or placement of an inorganic construct around the vessel. Cylindrical biocement scaffolds of differing chemistries were placed around the femoral vein. A contrast agent was used to visualize vessel ingrowth into the scaffolds. Cell populations in the scaffold were mapped using immunohistochemistry. Calcium phosphate scaffolds induced 2.7–3 times greater volume of blood vessels than calcium sulphate or magnesium phosphate scaffolds. Macrophage and vSMC populations were identified that changed spatially and temporally within the scaffold during implantation. NLRP3 inflammasome activation peaked at weeks 2 and 4 and then declined; however, IL-1β expression was sustained over the course of the experiment. IL-8, a promoter of angiogenesis, was also detected, and together, these responses suggest a role of sterile inflammation. Unexpectedly, the effect was distinct from an injury response as a result of surgical placement and also was not simply a foreign body reaction as a result of placing a rigid bioceramic next to a vein, since, while the materials tested had similar microstructures, only the calcium phosphates tested elicited an angiogenic response. This finding then reveals a potential path towards a new strategy for creating better pro-regenerative biomaterials. Full article

(This article belongs to the Special Issue Functionalized Biomimetic Calcium Phosphates 2.0)

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23 pages, 5590 KiB

Open AccessEditor’s ChoiceArticle

Antibacterial Electrodeposited Copper-Doped Calcium Phosphate Coatings for Dental Implants

by Camille Pierre, Ghislaine Bertrand, Iltaf Pavy, Olivier Benhamou, Christian Rey, Christine Roques and Christèle Combes

J. Funct. Biomater. 2023, 14(1), 20; https://doi.org/10.3390/jfb14010020 - 29 Dec 2022

Cited by 3 | Viewed by 1849

Abstract

Dental implants provide a good solution for the replacement of tooth roots. However, the full restoration of tooth functions relies on the bone-healing period before positioning the abutment and the crown on the implant, with the associated risk of post-operative infection. This study [...] Read more.

Dental implants provide a good solution for the replacement of tooth roots. However, the full restoration of tooth functions relies on the bone-healing period before positioning the abutment and the crown on the implant, with the associated risk of post-operative infection. This study aimed at developing a homogeneous and adherent thin calcium phosphate antibacterial coating on titanium dental implants by electrodeposition to favor both implant osseointegration and to limit peri-implantitis. By combining global (XRD, FTIR-ATR, elemental titration) and local (SEM, Raman spectroscopy on the coating surface and thickness) characterization techniques, we determined the effect of electrodeposition time on the characteristics and phases content of the coating and the associated mechanism of its formation. The 1-min-electrodeposited CaP coating (thickness: 2 ± 1 μm) was mainly composed of nano-needles of octacalcium phosphate. We demonstrated its mechanical stability after screwing and unscrewing the dental implant in an artificial jawbone. Then, we showed that we can reach a high copper incorporation rate (up to a 27% Cu/(Cu+Ca) molar ratio) in this CaP coating by using an ionic exchange post-treatment with copper nitrate solution at different concentrations. The biological properties (antibiofilm activity and cytotoxicity) were tested in vitro using a model of mixed bacteria biofilm mimicking peri-implantitis and the EN 10993-5 standard (direct contact), respectively. An efficient copper-doping dose was determined, providing an antibiofilm property to the coating without cytotoxic side effects. By combining the electrodeposition and copper ionic exchange processes, we can develop an antibiofilm calcium phosphate coating on dental implants with a tunable thickness and phases content. Full article

(This article belongs to the Special Issue Functionalized Biomimetic Calcium Phosphates 2.0)

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14 pages, 7472 KiB

Open AccessFeature PaperArticle

DLP Fabrication of Zirconia Scaffolds Coated with HA/β-TCP Layer: Role of Scaffold Architecture on Mechanical and Biological Properties

by Bartolomeo Coppola, Laura Montanaro and Paola Palmero

J. Funct. Biomater. 2022, 13(3), 148; https://doi.org/10.3390/jfb13030148 - 12 Sep 2022

Cited by 4 | Viewed by 2003

Abstract

In order to merge high-mechanical properties and suitable bioactivity in a single scaffold, zirconia porous structures are here coated with a hydroxyapatite layer. The digital light processing (DLP) technique is used to fabricate two types of scaffolds: simple lattice structures, with different sizes [...] Read more.

In order to merge high-mechanical properties and suitable bioactivity in a single scaffold, zirconia porous structures are here coated with a hydroxyapatite layer. The digital light processing (DLP) technique is used to fabricate two types of scaffolds: simple lattice structures, with different sizes between struts (750, 900 and 1050 µm), and more complex trabecular ones, these latter designed to better mimic the bone structure. Mechanical tests performed on samples sintered at 1400 °C provided a linear trend with a decrease in the compressive strength by increasing the porosity amount, achieving compressive strengths ranging between 128–177 MPa for lattice scaffolds and 34 MPa for trabecular ones. Scaffolds were successfully coated by dipping the sintered samples in a hydroxyapatite (HA) alcoholic suspension, after optimizing the HA solid loading at 20 wt%. After calcination at 1300 °C, the coating layer, composed of a mixture of HA and β-TCP (β-TriCalcium Phospate) adhered well to the zirconia substrate. The coated samples showed a proper bioactivity, well pronounced after 14 days of immersion into simulated body fluid (SBF), with a more homogeneous apatite layer formation into the trabecular samples compared to the lattice ones. Full article

(This article belongs to the Special Issue Functionalized Biomimetic Calcium Phosphates 2.0)

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23 pages, 8368 KiB

Open AccessEditor’s ChoiceArticle

Safe-by-Design Antibacterial Peroxide-Substituted Biomimetic Apatites: Proof of Concept in Tropical Dentistry

by Ika Dewi Ana, Any Lestari, Prescillia Lagarrigue, Jérémy Soulie, Rahmi Anggraeni, Françoise Maube-Bosc, Carole Thouron, Benjamin Duployer, Christophe Tenailleau and Christophe Drouet

J. Funct. Biomater. 2022, 13(3), 144; https://doi.org/10.3390/jfb13030144 - 07 Sep 2022

Cited by 7 | Viewed by 2253

Abstract

Bone infections are a key health challenge with dramatic consequences for affected patients. In dentistry, periodontitis is a medically compromised condition for efficient dental care and bone grafting, the success of which depends on whether the surgical site is infected or not. Present [...] Read more.

Bone infections are a key health challenge with dramatic consequences for affected patients. In dentistry, periodontitis is a medically compromised condition for efficient dental care and bone grafting, the success of which depends on whether the surgical site is infected or not. Present treatments involve antibiotics associated with massive bacterial resistance effects, urging for the development of alternative antibacterial strategies. In this work, we established a safe-by-design bone substitute approach by combining bone-like apatite to peroxide ions close to natural in vivo oxygenated species aimed at fighting pathogens. In parallel, bone-like apatites doped with Ag⁺ or co-doped Ag⁺/peroxide were also prepared for comparative purposes. The compounds were thoroughly characterized by chemical titrations, FTIR, XRD, SEM, and EDX analyses. All doped apatites demonstrated significant antibacterial properties toward four major pathogenic bacteria involved in periodontitis and bone infection, namely Porphyromonas gingivalis (P. gingivalis), Aggregatibacter actinomycetemcomitans (A. actinomycetemcomitans), Fusobacterium nucleatum (F. nucleatum), and S. aureus. By way of complementary tests to assess protein adsorption, osteoblast cell adhesion, viability and IC₅₀ values, the samples were also shown to be highly biocompatible. In particular, peroxidated apatite was the safest material tested, with the lowest IC₅₀ value toward osteoblast cells. We then demonstrated the possibility to associate such doped apatites with two biocompatible polymers, namely gelatin and poly(lactic-co-glycolic) acid PLGA, to prepare, respectively, composite 2D membranes and 3D scaffolds. The spatial distribution of the apatite particles and polymers was scrutinized by SEM and µCT analyses, and their relevance to the field of bone regeneration was underlined. Such bio-inspired antibacterial apatite compounds, whether pure or associated with (bio)polymers are thus promising candidates in dentistry and orthopedics while providing an alternative to antibiotherapy. Full article

(This article belongs to the Special Issue Functionalized Biomimetic Calcium Phosphates 2.0)

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18 pages, 4654 KiB

Open AccessFeature PaperEditor’s ChoiceArticle

When Nothing Turns Itself Inside out and Becomes Something: Coating Poly(Lactic-Co-Glycolic Acid) Spheres with Hydroxyapatite Nanoparticles vs. the Other Way Around

by Vuk Uskoković and Victoria M. Wu

J. Funct. Biomater. 2022, 13(3), 102; https://doi.org/10.3390/jfb13030102 - 23 Jul 2022

Cited by 2 | Viewed by 2117

Abstract

To stabilize drugs physisorbed on the surface of hydroxyapatite (HAp) nanoparticles and prevent burst release, these nanoparticles are commonly coated with polymers. Bioactive HAp, however, becomes shielded from the surface of such core/shell entities, which partially defeats the purpose of using it. The [...] Read more.

To stabilize drugs physisorbed on the surface of hydroxyapatite (HAp) nanoparticles and prevent burst release, these nanoparticles are commonly coated with polymers. Bioactive HAp, however, becomes shielded from the surface of such core/shell entities, which partially defeats the purpose of using it. The goal of this study was to assess the biological and pharmacokinetic effects of inverting this classical core/shell structure by coating poly(lactic-co-glycolic acid) (PLGA) spheres with HAp nanoparticles. The HAp shell did not hinder the release of vancomycin; rather, it increased the release rate to a minor degree, compared to that from undecorated PLGA spheres. The decoration of PLGA spheres with HAp induced lesser mineral deposition and lesser upregulation of osteogenic markers compared to those induced by the composite particles where HAp nanoparticles were embedded inside the PLGA spheres. This was explained by homeostatic mechanisms governing the cell metabolism, which ensure than the sensation of a product of this metabolism in the cell interior or exterior is met with the reduction in the metabolic activity. The antagonistic relationship between proliferation and bone production was demonstrated by the higher proliferation rate of cells challenged with HAp-coated PLGA spheres than of those treated with PLGA-coated HAp. It is concluded that the overwhelmingly positive response of tissues to HAp-coated biomaterials for bone replacement is unlikely to be due to the direct induction of new bone growth in osteoblasts adhering to the HAp coating. Rather, these positive effects are consequential to more elementary aspects of cell attachment, mechanotransduction, and growth at the site of contact between the HAp-coated material and the tissue. Full article

(This article belongs to the Special Issue Functionalized Biomimetic Calcium Phosphates 2.0)

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14 pages, 5070 KiB

Open AccessEditor’s ChoiceArticle

Hydroxyapatite Decorated with Tungsten Oxide Nanoparticles: New Composite Materials against Bacterial Growth

by Francesca Silingardi, Francesca Bonvicini, Maria Cristina Cassani, Raffaello Mazzaro, Katia Rubini, Giovanna Angela Gentilomi, Adriana Bigi and Elisa Boanini

J. Funct. Biomater. 2022, 13(3), 88; https://doi.org/10.3390/jfb13030088 - 24 Jun 2022

Cited by 6 | Viewed by 1892

Abstract

The availability of biomaterials able to counteract bacterial colonization is one of the main requirements of functional implants and medical devices. Herein, we functionalized hydroxyapatite (HA) with tungsten oxide (WO₃) nanoparticles in the aim to obtain composite materials with improved biological [...] Read more.

The availability of biomaterials able to counteract bacterial colonization is one of the main requirements of functional implants and medical devices. Herein, we functionalized hydroxyapatite (HA) with tungsten oxide (WO₃) nanoparticles in the aim to obtain composite materials with improved biological performance. To this purpose, we used HA, as well as HA functionalized with polyacrilic acid (HAPAA) or poly(ethylenimine) (HAPEI), as supports and polyvinylpyrrolidone (PVP) as stabilizing agent for WO₃ nanoparticles. The number of nanoparticles loaded on the substrates was determined through Molecular Plasma-Atomic Emission Spectroscopy and is quite small, so it cannot be detected through X-ray diffraction analysis. It increases from HAPAA, to HA, to HAPEI, in agreement with the different values of zeta potential of the different substrates. HRTEM and STEM images show the dimensions of the nanoparticles are very small, less than 1 nm. In physiological solution HA support displays a greater tungsten cumulative release than HAPEI, despite its smaller loaded amount. Indeed, WO₃ nanoparticles-functionalized HA exhibits a remarkable antibacterial activity against the Gram-positive Staphylococcus aureus in absence of cytotoxicity, which could be usefully exploited in the biomedical field. Full article

(This article belongs to the Special Issue Functionalized Biomimetic Calcium Phosphates 2.0)

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13 pages, 6622 KiB

Open AccessArticle

Monetite vs. Brushite: Different Influences on Bone Cell Response Modulated by Strontium Functionalization

by Elisa Boanini, Stefania Pagani, Matilde Tschon, Katia Rubini, Milena Fini and Adriana Bigi

J. Funct. Biomater. 2022, 13(2), 65; https://doi.org/10.3390/jfb13020065 - 24 May 2022

Cited by 10 | Viewed by 2573

Abstract

Monetite and brushite are regarded with increasing interest for the preparation of biomaterials for applications in the musculoskeletal system. Herein, we investigated the influence of strontium substitution in the structures of these two phosphates on bone cell response. To achieve this aim, co-cultures [...] Read more.

Monetite and brushite are regarded with increasing interest for the preparation of biomaterials for applications in the musculoskeletal system. Herein, we investigated the influence of strontium substitution in the structures of these two phosphates on bone cell response. To achieve this aim, co-cultures of human primary osteoclasts and human osteoblast-like MG63 cells were tested on strontium-substituted monetite and strontium-substituted brushite, as well as on monetite and brushite, as controls. In both structures, strontium substitution for calcium amounted to about 6 at% and provoked enlargement of the cell parameters and morphologic variations. Cumulative release in physiological solution increased linearly over time and was greater from brushite (up to about 160 and 560 mg/L at 14 days for Sr and Ca, respectively) than from monetite (up to about 90 and 250 mg/L at 14 days for Sr and Ca, respectively). The increasing viability of osteoblast-like cells over time, with the different expression level of some typical bone markers, indicates a more pronounced trigger toward osteoblast differentiation and osteoclast inhibition by brushite materials. In particular, the inhibition of cathepsin K and tartrate-resistant acid phosphatase at the gene and morphological levels suggests strontium-substituted brushite can be applied in diseases characterized by excessive bone resorption. Full article

(This article belongs to the Special Issue Functionalized Biomimetic Calcium Phosphates 2.0)

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Review

Jump to: Research

44 pages, 5628 KiB

Open AccessFeature PaperReview

Ion-Doped Calcium Phosphate-Based Coatings with Antibacterial Properties

by Marco Fosca, Alexandru Streza, Iulian V. Antoniac, Gianluca Vadalà and Julietta V. Rau

J. Funct. Biomater. 2023, 14(5), 250; https://doi.org/10.3390/jfb14050250 - 29 Apr 2023

Cited by 12 | Viewed by 3329

Abstract

Ion-substituted calcium phosphate (CP) coatings have been extensively studied as promising materials for biomedical implants due to their ability to enhance biocompatibility, osteoconductivity, and bone formation. This systematic review aims to provide a comprehensive analysis of the current state of the art in [...] Read more.

Ion-substituted calcium phosphate (CP) coatings have been extensively studied as promising materials for biomedical implants due to their ability to enhance biocompatibility, osteoconductivity, and bone formation. This systematic review aims to provide a comprehensive analysis of the current state of the art in ion-doped CP-based coatings for orthopaedic and dental implant applications. Specifically, this review evaluates the effects of ion addition on the physicochemical, mechanical, and biological properties of CP coatings. The review also identifies the contribution and additional effects (in a separate or a synergistic way) of different components used together with ion-doped CP for advanced composite coatings. In the final part, the effects of antibacterial coatings on specific bacteria strains are reported. The present review could be of interest to researchers, clinicians, and industry professionals involved in the development and application of CP coatings for orthopaedic and dental implants. Full article

(This article belongs to the Special Issue Functionalized Biomimetic Calcium Phosphates 2.0)

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