Abstract
Considerable advances in tissue engineering and regeneration have been accomplished over the last decade. Bioceramics have been developed to repair, reconstruct, and substitute diseased parts of the body and to promote tissue healing as an alternative to metallic implants. Applications embrace hip, knee, and ligament repair and replacement, maxillofacial reconstruction and augmentation, spinal fusion, bone filler, and repair of periodontal diseases. Bioceramics are well-known for their superior wear resistance, high stiffness, resistance to oxidation, and low coefficient of friction. These specially designed biomaterials are grouped in natural bioceramics (e.g., coral-derived apatites), and synthetic bioceramics, namely bioinert ceramics (e.g., alumina and zirconia), bioactive glasses and glass ceramics, and bioresorbable calcium phosphates-based materials. Physicochemical, mechanical, and biological properties, as well as bioceramics applications in diverse fields of tissue engineering are presented herein. Ongoing clinical trials using bioceramics in osteochondral tissue are also considered. Based on the stringent requirements for clinical applications, prospects for the development of advanced functional bioceramics for tissue engineering are highlighted for the future.
Keywords
1 Introduction
Over the last century, new biomaterials have considerably changed the lives of millions of patients. Biomaterials have made an important contribution to modern health care and will expand further, especially for osteoporosis, osteoarthritis, and fragility fractures, increasing with elderly population. Each biomaterial has specific physicochemical, mechanical, and biological characteristics which can originate variations in host/material response when applied for healthcare.
Bioceramics can be classified as inorganic and non-metallic ceramics used for the repair and regeneration of diseased and damaged parts of the musculoskeletal system and periodontal anomalies [1]. Bioceramics are known to promote biomineralization with excellent osteoconductivity, chemical corrosion resistance, and a hard brittle surface. However, limitations include brittleness, poor fracture toughness, very low elasticity, and extremely high stiffness [2]. Bioceramics are categorized depending on their ability to bond with living tissues after implantation, as: (a) bioinert ceramics (e.g., alumina and zirconia) has no interaction with its surrounding tissue after implantation. They have a reasonable fracture toughness, and resistance to corrosion and wear, (b) bioactive ceramics (e.g., bioglasses and glass-ceramics) bond directly with living tissues, with the pattern of bonding osteogenesis, and (c) bioresorbable ceramics (e.g., calcium phosphates (CaPs), calcium phosphate cements (CPCs), calcium carbonates, and calcium silicates) are gradually absorbed in vivo and is replaced by bone with time.
Considering their unique properties, bioceramics are commonly used in tissue engineering (TE) and biomedical applications, particularly for developing 3D–based scaffolds able to mimic the native tissues [3, 4]. Bioceramics are stronger under compression and weak under tension, important facts to have into account in particular biomedical application. Natural and synthetic bioceramics have been proposed to be used in the processing TE scaffolding considering specific composition, microstructure, and long-term reproducibility. Natural bioceramics include coral-derived materials, sponges, nacres, and animal (fish and chicken) bones, and offer an abundant source of calcium compounds (e.g., calcium carbonate and calcium phosphate) [5]. Synthetic bioceramics embrace alumina and zirconia, bioactive porous glasses and glass-ceramics, and CaPs-based materials in the form of sintered ceramics, coatings and cement pastes [6, 7].
Fabrication methodology available for bioceramics production are wet precipitation, hydrolysis, sol–gel synthesis, hydrothermal synthesis, mechanochemical synthesis, microwave processing, and spray drying methods. Among them, wet precipitation method has the benefit on the homogeneity of the final product, and the easiness of controlling certain parameters, such as temperature, pH, and the presence of additives, during the synthesis [8].
Many studies are devoted to bioceramics incorporating ionic elements (e.g., strontium, zinc, magnesium, manganese, and silicon) that would be released during bone graft resorption, and hence can influence bone health and enhance biocompatibility, while strengthening the mechanical properties of the implants [9,10,11,12,13]. Besides, minerals and traces of metal elements may provide physicochemical modifications in the produced materials, which can accelerate bone formation and resorption in vivo [14, 15].
This chapter presents a concise overview of natural and synthetic bioceramic materials for bone, cartilage, and OC tissue applications. A variety of materials are considered, from bioinert to bioactive and bioresorbable ceramics. It is presented their physicochemical, mechanical and biological properties. Clinical trials involving bioceramics, challenges and future prospects of research in this field, are also underlined.
2 Bioceramic Materials and Properties
2.1 Natural Bioceramics
Naturally derived bioceramics can offer an abundant source of inorganic materials (e.g., calcium carbonate and CaPs) with high applicability for tissue replacement and regeneration [5]. Emphasis are put on the ones from marine origin, such as natural corals, nacres (or mollusc shells), sponges, and fish bones (Fig. 3.1I). Calcium carbonate (aragonite or calcite forms) can be found in many of these marine organisms, and then converted to CaPs for the biomedical field, owing their unique structure, architecture, and mechanical properties.
Corals have been the most widely investigated as scaffolds, since they combine a multiscale porosity, and interconnected pores (100–500 μm diameter) and channels, crucial for healthy bone replacement [16]. Also, coral skeletons hold in situ resorption and high versatility, thus be capable of genes and bioactive factors delivering. Our group reported the use of Coralline officinallis to be useful as bone fillers targeting its repair and regeneration [17, 18]. Calcium carbonate skeletons of C. officinallis were converted into CaPs with hydroxyapatite (HAp) nanocrystallites, by combining a thermal and chemical treatment (Fig. 3.1II) [17]. Results showed that the coralline particulates preserved their morphology, after heat treatment and by soaking in different solutions. Furthermore, it was demonstrated that it was possible to tailor the microstructure of coralline, as well as the bioactivity and degradation profile.
2.2 Synthetic Bioceramics
2.2.1 Bioinert Materials
Alumina (Al2O3) and Zirconia (ZrO2) are chemically inert and have high mechanical resistance, high hardness, and are resistant to cracking and corrosion. They are bioinert ceramics, successfully used in orthopedics, specifically for total hip/knee arthroplasty and in dentistry (Fig. 3.2) [20, 21].
Alumina-based bioceramics were the first to be available in the market, for dental implants and acetabular cup replacements in total hip prostheses [22]. Alumina positively combines good flexural and mechanical strength, excellent resistance to dynamic and fatigue, and high resistance to abrasion. As a result, alumina has been effectively used as synthetic bone grafts and as reinforcement agents for ceramics, or even as porous prosthetic devices, by means of a biomimetic coating on alumina, to afford a stable bond with the host tissue. Other clinical applications of alumina prostheses include bone screws, alveolar ridge (jaw bone) and maxillofacial reconstruction, ossicular (middle ear) bone substitutes, corneal replacements, segmental bone replacements, and blade, screw, and post-type dental implants [23]. However, alumina ceramics have a low toughness to fracture. This disadvantage can be overcome if zirconia is added to alumina ceramics (known as zirconia-toughened alumina, ZTA, or alumina-toughened zirconia, ATZ), resulting in a composite material with higher toughness and better tribological properties [24, 25]. ZTA contains alumina (70–95%) as the matrix phase and zirconia polycrystals (TZP, 5–30%) as the secondary phase, combining the positive properties of monolithic alumina with zirconia. Moreover, the wear properties and low susceptibility to stress-assisted degradation of alumina ceramics are also preserved in ZTA ceramics, reducing the risk of impingement and dislocation, and improving stability [25].
Zirconia has a polymorphic crystalline structure depending on the temperature, i.e., monoclinic at temperatures <1170 °C, tetragonal at 1170 °C which is stable up to 2370 °C, and cubic structure at 2370 °C. However, this phase transformation also occurs at the surface of the ceramic when present in body fluid, producing an aging which compromises the lifetime of zirconia implants. As a result zirconia-based bioceramics, especially tetragonal TZP, have been widely used in bone TE, due to their excellent toughness to fracture , high strength, high elastic modulus, wear resistance, and low temperature degradation [26]. For example, partially stabilized zirconia (with yttria, CaO, and MgO) materials are recognized for their flexural strength (higher than 1.0 GPa) and fracture toughness (above 8 MPam1/2) [27, 28]. Besides its mechanical properties, zirconia promotes cell proliferation and differentiation in osteogenic pathways and osseointegration. Also, as it is radiopaque, it helps in the monitoring of radiographs [29]. Zirconia has often been used in dentistry since it can be colored to match the shade of existing teeth.
2.2.2 Bioactive Glasses and Glass-Ceramics
Bioactive glasses and glass-ceramics have been developed, in dense and porous form, for TE applications in orthopedics and dentistry (Fig. 3.3) [32,33,34]. Heat treated glasses result in crystalline glasses with higher strength and toughness, elastic modulus, and wear resistance.
Bioactive glasses have demonstrated their appropriateness to form a bond with the living bone tissue more rapidly than other bioceramics. They are converted into an amorphous CaP or apatite material after implantation. Moreover, it has also been reported that the ions Si, Ca, P, and Na, released during dissolution of certain bioactive glasses, seem to activate the expression of osteogenic genes and to stimulate neovascularization and angiogenesis, enzymatic activity, and differentiation of mesenchymal stem cells (MSCs) [35,36,37].
In the 1970s, Larry Hench [23] undertook the pioneering work in the field of bioactive glasses for biomedical applications with the development of 45S5 Bioglass®. It is a silica-based bioactive glass in the Na2O–CaO–SiO2–P2O5 system with a composition near the ternary eutectic in the Na2O–CaO–SiO2 diagram. Upon implantation, this unique biomaterial releases soluble Si2+, Ca2+, and P ions into solution, forming a hydroxycarbonate surface layer through a biochemical transformation. The dissolution of the ions of the bioactive glasses stimulates the genes responsible for osteoblast differentiation and proliferation [34, 38, 39]. Besides, it also combines the advantage of having an antimicrobial (ions increase the pH resulting in an osmotic effect), and an angiogenic activity, as well as stimulates the release of angiogenetic growth factors [33]. For example, when 45S5 Bioglass® was used in medium conditioned for fibroblasts there was an increase in tubule branching and the development of a complex network [40].
Besides the conventional silicate glasses, other types of bioactive glasses developed for biomedical applications include borate-based and phosphate-based glasses. Borate-based glasses, in the B2O3–Na2O–CaO–P2O5 system, have fast degradation rates and are able to be completely converted into apatite when immersed in an aqueous phosphate solution, following a similar process of Bioglass®, but without the formation of a silica-rich layer [41, 42]. Borate glasses have also been used as drug release systems in the treatment of bone infection [43]. A disadvantage of this type of glasses is the toxicity of boron, which is released in the solution as borate ions; this disadvantage can be overturned in in vitro dynamic culture conditions [44]. Phosphate bioactive glasses, in the Na2O–CaO–P2O5 system, have faster dissolution rates in aqueous fluids than silica glasses, which is a useful property for the healing of chronic wounds and as carriers in drug delivery, such as antibacterial ions and complex organic molecules for chemotherapy applications [45, 46]. The incorporation of metal oxides such as TiO2, Al2O3, and B2O3 into the composition of phosphate glasses can stabilize the glass network, resulting in a slower degradation of the glass [24].
The common synthesis methods for bioactive glasses include the conventional melt-quenching, sol–gel process, flame spray synthesis, and microwave irradiation [47, 48].
2.2.3 Calcium Phosphates
Calcium phosphates (CaPs) are naturally found in the body and are bone-like materials proposed for a broad range of orthopedic and dental applications owing the similarity with the mineral component of major normal calcified tissues [51,52,53]. These types of bioceramics possess an outstanding biocompatibility, osteoconductivity, and bioresorbability, thus integrating into living tissues by the same processes active in bone remodeling. This phenomenon occurs when part of CaPs is dissolved into the microenvironment, and once the liberated ions are released, protein adsorption and precipitation of the biological apatite crystals takes place creating a layer on the surface of the biomaterial. Besides, CaPs are easy to obtain with a low cost, and can be relatively easily certified as medical grade. The most known CaPs comprise compounds with different chemical compositions, solubility, and properties (Table 3.1). CaPs can be ordered by in situ degradation rate as: MCPM > TTCP ≈ α-TCP > DCPD > OCP > β-TCP > HAp [54]. Differences in dissolution behavior of CaPs are related to changes in the chemical composition, as well as, the microporosity, and pore size, and have been connected with the process of osteoinduction in vivo [55]. Studies have shown the importance of the sintering process as a way to control the pore size and porosity, thus rendering an osteoinductive ceramic [56].
Despite that, CaPs are limited to load-bearing applications due to their poor mechanical properties, namely, strength and fatigue resistance, and for this reason they are mostly used as coatings and as fillers [51, 57]. However, CaPs bioceramics varied from thin coatings on metallic implants to help fixation into bone, to dense or porous blocks to be used as bone grafts, or even as injectable compositions (Fig. 3.4). Custom-designed forms as wedges for tibial opening osteotomy, cones for spine and knee, and inserts for vertebral cage fusion, are also available. CaPs are used in alveolar ridge augmentation, tooth replacement, maxillofacial reconstruction, orbital implants, increment of the hearing ossicles, spine fusion, and repair of bone defects [58].
Among CaPs most commonly investigated for biomedical purposes are α- and β-TCP, CDHA, HAp, and biphasic CaPs which is the mixture of HAp and TCP [51, 59]. HAp is crystalline and is the most stable and least soluble CaPs in an aqueous solution below pH 4.2 [51]. HAp can be produced through wet methods, such as precipitation method, hydrothermal synthesis and solid-state reaction above 1200 °C of, for example, MCPM, DCPA, DCPD, OCP [60,61,62,63]. β-TCP is a high temperature phase of CaPs, obtained by thermal decomposition at temperatures above 800 °C. TCP can occur under three recognized polymorphs, such as β-TCP stable below 1120 °C, α-TCP stable between 1120 °C and 1470 °C, and α’-TCP above 1470 °C. Generally, β-TCP densification is difficult because the low temperature of β → α phase transformation does not permit the sintering to high temperature. However, doping β-TCP with magnesia or calcium pyrophosphate can stabilize this β → α transition at high temperatures. β-TCP is biodegradable and has been extensively investigated as bone substitute, either as granules or blocks, or even in CaPs-based bone cements [52]. α-TCP is usually prepared from β-TCP phase, and quenching it prevents the reverse transformation α → β [64]. α-TCP is biocompatible, and more biodegradable and reactive than β-TCP [65]. It has been reported that the biological resorption capability of β-TCP and HAp is different though their similarity in terms of chemical composition. HAp has a slow resorption rate and may remain integrated into the regenerated bone tissue after implantation, whereas β-TCP is completely reabsorbed [66, 67]. Hence, biomaterials for clinical applications have been performed combining HAp and β-TCP, for the bioresorbability and strength improvement of the implants [59, 63, 68]. CDHA is obtained by precipitation in an aqueous solution above a pH 7 [51]. Their crystals are in general poorly crystalline and of submicron dimensions. The solubility of CDHA increases with a decrease of Ca–P molar ratio, crystallinity, and size. CDHA can decompose into β-TCP, into a mixture of HAp and β-TCP or into pure HAp, when heating above 700 °C [59, 69]. As a first approximation, CDHA may be considered as HAp with some ions missing [70].
Calcium phosphates-based cements (CPCs) are mixture of one or several CaPs and an aqueous solution, which then precipitate into a less soluble CaP and sets by the entanglement of the growing crystals, providing mechanical stiffness to the cement. Once placed into the bone defect, the paste hardens in situ, at body temperature, and then displays limited solubility (Fig. 3.5) [72]. CPCs relevant features are excellent biocompatibility and resorbability, bioactivity, non-cytotoxicity, development of osteoconductive pathways, and sufficient compressive strength for a number of applications [51, 66, 73, 74]. CPCs are mechanically much stronger in compression than in tension or shear, because entangled crystals are not well bonded. Compressive strength values are typically 5–10 times superior to that of tensile. The main advantages of the CPCs include fast setting, excellent moldability, and manipulation. Hence, these bioceramics are commonly used to fill bone defects and trauma surgeries as moldable paste-like bone substitute materials. Besides, like any other bioceramics, CPCs provide the opportunity for bone grafting using alloplastic materials, which are unlimited in quantity and provide no risk of infectious diseases.
CPCs can be classified according to their end product into apatite (AP) cements and dicalcium phosphate dehydrate (DCPD or brushite) cements, upon the pH value of a cement paste after setting. AP is formed above pH 4.2, whereas brushite is preferentially formed when pH value of the paste is <4.2, although it may grow even up to pH 6.5, due to kinetics reasons [75, 76]. Brushite cements have raised interest due to their higher solubility and resorbability in vivo much faster than AP cements. Although AP cements show higher mechanical strength, they have slow in vivo resorption rates that interfere with the bone regeneration process [77, 78]. Moreover, brushite-based cements possess faster setting reactions [9, 79].
3 Applications of Bioceramics in Osteochondral Tissue Engineering
Current clinical use of bioceramics for bone, cartilage, and OC repair include, bone grafting, microfracture, arthroscopic mosaicplasty, periosteal and perichondrial transplantation, autologous chondrocyte implantation, drug delivery, and gene transfection [82,83,84]. Despite the fact that autologous grafts are the most ideal treatment, the rate of morbidity and the difficulty in trimming and grafting for the desired shape are important drawbacks of this technique [85,86,87].
Growth factors integration , like bone morphogenic proteins (BMPs) , into scaffold, through structural entrapment or surface complexes have been widely reported for bone growth and healing, for instance in long bone defects, for their osteoinduction ability. Growth factors play a major role in cellular guiding and control. The incorporation of stem cells, like bone marrow stromal stem cells (BMSCs) or mesenchymal stem cells (MSCs), in bioceramics scaffolds for OC defects repairs, have been studied, since these cells had demonstrated promising results in bone recovery [88, 89]. For example, Lv and Yu [90] studied the viability of a composite lamellar scaffold made of nano-β-TCP)/collagen type I and type II with BMSCs, for the articular OC defects repair in canine knee joints. In articular OC defects, subchondral bone plays an important role, once it is responsible for the formation of bones outline shape and provides the biomechanical needed environment cartilage differentiation and development. Thus, the biphasic composite scaffold used consisted of a mineralized collagen type I/β-TCP scaffold for bone regeneration and a non-mineralized collagen type II/β-TCP scaffold for cartilage regeneration. That study showed a gradual degradation and absorption of the scaffolds, while new cartilage tissue was formed. After 24 weeks of implantation, the defect space was fulfilled with new cartilage tissue integrated in the surrounding cartilage.
Several bioceramics and polymer composites have been developed and reported as an attractive solution for the repair of OC injuries . Xue et al. [91] evaluated the use of a poly-(lactide-co-glycolide) (PLGA)/nano HAp scaffold for potential use in cartilage tissue engineering applications. For that, MSCs were seeded in scaffolds and their efficacy was evaluated on a rat model. After 12 weeks after implantation, it was possible to observe that OC defects in rat knees were filled with smooth and hyaline-like cartilage with glycosaminoglycan and collagen type II deposition. Results were compared to those obtained only for PLGA scaffolds and, PLGA/nano HAp hybrid scaffold facilitated more significantly the cartilage repair, and provided a higher viability and proliferation of MSCs. In another study by Oliveira et al. [92] was reported the development of a porous HAp scaffolds with high interconnectivity, using an organic sacrifice template, for bone regeneration/repair. The scaffolds were tested in vitro, using rat bone marrow stromal cells (rBMSCs) confirmed that the cells adhered, proliferated well and remained viable (Fig. 3.6).
Zylinska et al. [93] also took advantaged from polymers and HAp and evaluated the applicability of a poly-L/D-lactide (PLDLA)/nano HAp composite scaffold enriched with sodium alginate in OC lesions of rabbit femoral trochlea. The use of sodium alginate is limited due to its low mechanical strength and fast degeneration. Thus, combining sodium alginate with PLDLA/nano HAp scaffold overcome these limitations, and the incorporation of the nano-sized HAp provides bioactivity, osteoinductivity and osteoconductivity, which facilitated new bone tissue regeneration. The bioactivity of the composites is low on the initial phase, increasing over time, due to its biodegradation.
Taking advantage of naturally derived polymers, a study reported the development of a biphasic scaffold using silk fibroin and strontium-hardystonite-gahnite ceramic with stratified structure composed of distinct cartilage and bone phases which were well-integrated at a continuous interface, to satisfy the complex and diverse regenerative requirements of OC tissue [94]. Microstructure analysis showed that the cartilage phase had pores highly interconnected with sizes of 100–120 µm, while the bone phase had large pore sizes of 400–500 µm, along with interconnectivity (Fig. 3.7 I). In vitro behaviour of human mesenchymal stem cells (hMSCs) cultured in the scaffolds indicated that the cells infiltrated throughout its entire structure by allowing cell migration within and between phases. The SEM images showed that the scaffold was biocompatible and provided favourable substrates for cell attachment in its cartilage and bone phases, as well as a continuous interface which allowed cell migration and interaction between phases (Fig. 3.7 II).
In Table 3.2 are summarized diverse bioceramics materials used for bone, cartilage, and OC applications.
4 Clinical Trials of Bioceramics for Osteochondral Regeneration
Human clinical trials are research studies worldwide which evaluate the safety and effectiveness of a medical strategy, treatment, or device for humans. These studies follow strict scientific standards and are only performed after the approval of the health ethics committee. These standards are designed to protect patients and help to produce reliable study results. Those results are only obtained after a long and careful process which begins in the laboratory, following by animal tests and, as final stage come to clinical trials [102]. In Table 3.3 are reported the completed and ongoing clinical trials of using different types of bioceramics for OC applications.
Before their commercialization , implantable devices went through a rigorous, long and detailed process, involving several stages of R&D under restrict guidance of FDA. During this process, the safety of the medical device is ensured, and validated by scientific evidences, and after the approval, they are classified according with the associated risk. For instance, medium risk Class II devices include fracture fixation devices, while devices for organs replacement are in high risk Class III [102].
There are already some engineered bioceramic based materials and scaffolds regulatory approved as: (a) bone grafts substitutes , namely CERAMENT™G, Bonalive (Vivoxid Ltd), NovoMax® (BioAlpha Inc.,), ChronOs (DePuySynthes), Straumann® BoneCeramic™, and Geistlich Bio-Oss®; (b) cartilage repair, namely Cartilage Repair Device (Kensey Nash Corporation), and (c) OC defects such as ChondroMimetic ®, MaioRegen®, and Agili-CTM.
5 Concluding Remarks and Future Outlook
Bioceramics have demonstrated very important successes for applications in orthopedic and dental surgery. They are, however, potentially suitable for a wide range of essential TE purposes, namely, to restore the natural state and function of damaged OC tissue. Advanced strategies present some of the current challenges in this field, and may constitute a major step forward in the future. Bioceramics offer desirable characteristics such as biocompatibility, chemical inertness in biological medium, and hardness, but they have low resistance to traction. Ongoing research involves the chemistry, composition, and microstructure and nanostructure of the materials to improve their mechanical integrity upon implantation, and appropriate porosity for the cellular adhesion, proliferation, and differentiation. Although there have been significant advances in engineer new tissues, developments aimed at designing materials perfectly matching their biomedical purposes are necessary. Strategies should be devoted on the clear understanding of the bioceramics–tissue interactions, and hierarchical structure for long-term service, and the related mechanical strength, especially the fatigue limit under periodic external stress.
References
Salinas AJ, Vallet-Regi M (2013) Bioactive ceramics: from bone grafts to tissue engineering. RSC Adv 3(28):11116–11131. https://doi.org/10.1039/C3RA00166K
Hasan MS, Ahmed I, Parsons AJ, Rudd CD, Walker GS, Scotchford CA (2013) Investigating the use of coupling agents to improve the interfacial properties between a resorbable phosphate glass and polylactic acid matrix. J Biomater Appl 28(3):354–366. https://doi.org/10.1177/0885328212453634
Pina S, Oliveira JM, Reis RL (2015) Natural-based Nanocomposites for bone tissue engineering and regenerative medicine: a review. Adv Mater 27(7):1143–1169. https://doi.org/10.1002/adma.201403354
Yan LP, Silva-Correia J, Correia C, Caridade SG, Fernandes EM, Sousa RA, Mano JF, Oliveira JM, Oliveira AL, Reis RL (2013) Bioactive macro/micro porous silk fibroin/nano-sized calcium phosphate scaffolds with potential for bone-tissue-engineering applications. Nanomedicine (Lond) 8(3):359–378. https://doi.org/10.2217/nnm.12.118
Silva TH, Alves A, Ferreira BM, Oliveira JM, Reys LL, Ferreira RJF, Sousa RA, Silva SS, Mano JF, Reis RL (2012) Materials of marine origin: a review on polymers and ceramics of biomedical interest. Int Mater Rev 57(5):276–306. https://doi.org/10.1179/1743280412Y.0000000002
Oliveira J, Costa S, Leonor I, Malafaya P, Mano J, Reis R (2009) Novel hydroxyapatite/carboxymethylchitosan composite scaffolds prepared through an innovative "autocatalytic" electroless coprecipitation route. J Biomed Mater Res A 88:470–480
Oliveira JM, Kotobuki N, Tadokoro M, Hirose M, Mano JF, Reis RL, Ohgushi H Ex vivo culturing of stromal cells with dexamethasone-loaded carboxymethylchitosan/poly(amidoamine) dendrimer nanoparticles promotes ectopic bone formation. Bone 46(5):1424–1435. doi:https://doi.org/10.1016/j.bone.2010.02.007
Fomin A, Barinov S, Ievlev V, Smirnov V, Mikhailov B, Belonogov E, Drozdova N (2008) Nanocrystalline hydroxyapatite ceramics produced by low-temperature sintering after high-pressure treatment. Doklady Chem 418:22–25
Pina S, Ferreira J (2010) Brushite-forming Mg-, Zn- and Sr-substituted bone cements for clinical applications. Materials 3:519–535
Tomoaia G, Mocanu A, Vida-Simiti I, Jumate N, Bobos LD, Soritau O, Tomoaia-Cotisel M (2014) Silicon effect on the composition and structure of nanocalcium phosphates: in vitro biocompatibility to human osteoblasts. Mater Sci Eng C Mater Biol Appl 37:37–47. https://doi.org/10.1016/j.msec.2013.12.027
Vallet-Regi M, Arcos D (2005) Silicon substituted hydroxyapatites. A method to upgrade calcium phosphate based implants. J Mater Chem 15(15):1509–1516
Kose N, Otuzbir A, Peksen C, Kiremitci A, Dogan A (2013) A silver ion-doped calcium phosphate-based ceramic nanopowder-coated prosthesis increased infection resistance. Clin Orthop Relat Res 471(8):2532–2539. https://doi.org/10.1007/s11999-013-2894-x
LeGeros RZ, Kijkowska R, Bautista C, Retino M, LeGeros JP (1996) Magnesium incorporation in apatites: effect of CO3 and F. J Dent Res 75:60–60
Mestres G, Le Van C, Ginebra M-P (2012) Silicon-stabilized α-tricalcium phosphate and its use in a calcium phosphate cement: characterization and cell response. Acta Biomater 8(3):1169–1179. https://doi.org/10.1016/j.actbio.2011.11.021
Pina S, Vieira SI, Rego P, Torres PMC, Goetz-Neunhoeffer F, Neubauer J, da Cruz e Silva OAB, da Cruz e Silva EF, Ferreira JMF (2010) Biological responses of brushite-forming Zn- and ZnSr-substituted β-TCP bone cements. Eur Cells Mater (in press) 20:162–177
Green DW, Ben-Nissan B, Yoon KS, Milthorpe B, Jung H-S (2017) Natural and synthetic coral biomineralization for human bone revitalization. Trends Biotechnol 35(1):43-54. doi:10.1016/j.tibtech.2016.10.003
Oliveira JM, Grech JMR, Leonor IB, Mano JF, Reis RL (2007) Calcium-phosphate derived from mineralized algae for bone tissue engineering applications. Mater Lett 61:3495–3499
Correlo VM, Oliveira JM, Mano JF, Neves NM, Reis RL (2011) Chapter 32 - Natural origin materials for bone tissue engineering—properties, processing, and performance A2 - Atala, Anthony. In: Lanza R, Thomson JA, Nerem R (eds) Principles of regenerative medicine (second edition). Academic, San Diego, pp 557–586. doi:https://doi.org/10.1016/B978-0-12-381422-7.10032-X
Clarke SA, Walsh P, Maggs CA, Buchanan F (2011) Designs from the deep: marine organisms for bone tissue engineering. Biotechnol Adv 29(6):610–617. doi:https://doi.org/10.1016/j.biotechadv.2011.04.003
Maccauro G, Iommetti PR, Raffaelli L, Manicone PF (2011) Alumina and zirconia ceramic for orthopaedic and dental devices. In: Biomaterials applications for nanomedicine. InTech
Ghaemi MH, Reichert S, Krupa A, Sawczak M, Zykova A, Lobach K, Sayenko S, Svitlychnyi Y (2017) Zirconia ceramics with additions of Alumina for advanced tribological and biomedical applications. Ceramics Int 43(13):9746-9752. doi:https://doi.org/10.1016/j.ceramint.2017.04.150
Kolos E, Ruys A (2015) Biomimetic coating on porous alumina for tissue engineering: characterisation by cell culture and confocal microscopy. Materials 8(6):3584
Greenspan DC (2016) Glass and medicine: the Larry Hench story. Int J Appl Glas Sci 7(2):134–138. https://doi.org/10.1111/ijag.12204
Biamino S, Fino P, Pavese M, Badini C (2006) Alumina–zirconia–yttria nanocomposites prepared by solution combustion synthesis. Ceram Int 32(5):509–513. https://doi.org/10.1016/j.ceramint.2005.04.004
Kurtz SM, Kocagöz S, Arnholt C, Huet R, Ueno M, Walter WL (2014) Advances in zirconia toughened alumina biomaterials for total joint replacement. J Mech Behav Biomed Mater 31:107–116. https://doi.org/10.1016/j.jmbbm.2013.03.022
Pieralli S, Kohal RJ, Jung RE, Vach K, Spies BC (2016) Clinical outcomes of zirconia dental implants: a systematic review. J Dent Res 96(1):38–46. https://doi.org/10.1177/0022034516664043
Nakamura K, Adolfsson E, Milleding P, Kanno T, Örtengren U (2012) Influence of grain size and veneer firing process on the flexural strength of zirconia ceramics. Eur J Oral Sci 120(3):249–254. https://doi.org/10.1111/j.1600-0722.2012.00958.x
Benzaid R, Chevalier J, Saâdaoui M, Fantozzi G, Nawa M, Diaz LA, Torrecillas R (2008) Fracture toughness, strength and slow crack growth in a ceria stabilized zirconia–alumina nanocomposite for medical applications. Biomaterials 29(27):3636–3641. https://doi.org/10.1016/j.biomaterials.2008.05.021
Afzal A (2014) Implantable zirconia bioceramics for bone repair and replacement: a chronological review. Mater Express 4(1):1–12. https://doi.org/10.1166/mex.2014.1148
http://www.nevz-ceramics.com/en/produktyi-i-materialyi/biokeramika.html
Rawlings RD (1993) Bioactive glasses and glass-ceramics. Clin Mater 14(2):155–179. https://doi.org/10.1016/0267-6605(93)90038-9
Rahaman MN, Day DE, Sonny Bal B, Fu Q, Jung SB, Bonewald LF, Tomsia AP (2011) Bioactive glass in tissue engineering. Acta Biomater 7(6):2355–2373. https://doi.org/10.1016/j.actbio.2011.03.016
Jones JR (2013) Review of bioactive glass: from Hench to hybrids. Acta Biomater 9(1):4457–4486. https://doi.org/10.1016/j.actbio.2012.08.023
Lobel KD, Hench LL (1996) In-vitro protein interactions with a bioactive gel-glass. J Sol-Gel Sci Technol 7(1–2):69–76. https://doi.org/10.1007/BF00401885
Gorustovich AA, Roether JA, Boccaccini AR (2010) Effect of bioactive glasses on angiogenesis: a review of in vitro and in vivo evidences. Tissue Eng Part B Rev 16(2):199–207. https://doi.org/10.1089/ten.teb.2009.0416
Xynos ID, Edgar AJ, Buttery LDK, Hench LL, Polak JM (2000) Ionic products of bioactive glass dissolution increase proliferation of human osteoblasts and induce insulin-like growth factor II mRNA expression and protein synthesis. Biochem Biophys Res Commun 276(2):461–465. https://doi.org/10.1006/bbrc.2000.3503
Hench LL (1998) Bioceramics. J Amer Ceram Soc 81:1705–1728
Huang W, Day D, Kittiratanapiboon K, Rahaman M (2006) Kinetics and mechanisms of the conversion of silicate (45S5), borate, and borosilicate glasses to hydroxyapatite in dilute phosphate solutions. J Mater Sci Mater Med 17(7):583–596. https://doi.org/10.1007/s10856-006-9220-z
Leu A, Leach JK (2008) Proangiogenic potential of a collagen/bioactive glass substrate. Pharm Res 25(5):1222–1229. https://doi.org/10.1007/s11095-007-9508-9
Fu Q, Rahaman MN, Fu H, Liu X (2010) Silicate, borosilicate, and borate bioactive glass scaffolds with controllable degradation rate for bone tissue engineering applications. I. Preparation and in vitro degradation. J Biomed Mater Res A 95(1):164–171. https://doi.org/10.1002/jbm.a.32824
Knowles JC (2003) Phosphate based glasses for biomedical applications. J Mater Chem 13(10):2395–2401. https://doi.org/10.1039/B307119G
Xie Z, Cui X, Zhao C, Huang W, Wang J, Zhang C (2013) Gentamicin-loaded borate bioactive glass eradicates osteomyelitis due to Escherichia Coli in a rabbit model. Antimicrob Agents Chemother 57(7):3293–3298. https://doi.org/10.1128/AAC.00284-13
Brown RF, Rahaman MN, Dwilewicz AB, Huang W, Day DE, Li Y, Bal BS (2009) Effect of borate glass composition on its conversion to hydroxyapatite and on the proliferation of MC3T3-E1 cells. J Biomed Mater Res A 88A(2):392–400. https://doi.org/10.1002/jbm.a.31679
Marikani A, Maheswaran A, Premanathan M, Amalraj L (2008) Synthesis and characterization of calcium phosphate based bioactive quaternary P2O5–CaO–Na2O–K2O glasses. J Non-Cryst Solids 354(33):3929–3934. https://doi.org/10.1016/j.jnoncrysol.2008.05.005
Pickup DM, Newport RJ, Knowles JC (2010) Sol–gel phosphate-based glass for drug delivery applications. J Biomater Appl 26(5):613–622. https://doi.org/10.1177/0885328210380761
Kashif I, Soliman AA, Sakr EM, Ratep A (2012) Effect of different conventional melt quenching technique on purity of lithium niobate (LiNbO3) nano crystal phase formed in lithium borate glass. Results Phys 2(0):207–211. https://doi.org/10.1016/j.rinp.2012.10.003
Balamurugan A, Rebelo A, Kannan S, Ferreira JMF, Michel J, Balossier G, Rajeswari S (2007) Characterization and in vivo evaluation of sol–gel derived hydroxyapatite coatings on Ti6Al4V substrates. J Biomed Mater Res B Appl Biomater 81B(2):441–447. https://doi.org/10.1002/jbm.b.30682
Brunner TJ, Stark WJ, Grass RN (2006) Glass and bioactive glass Nanopowders by flame synthesis. AIChE Annual Meeting, Hilton San Francisco
http://ceramics.org/ceramic-tech-today/biomaterials/glass-scaffolds-help-heal-bone
Bohner M (2000) Calcium orthophosphates in medicine: from ceramics to calcium phosphate cements. Injury Int J Care Injured 31:37–47
Dorozhkin S (2009) Calcium orthophosphates in nature, biology and medicine. Materials 2:399–498
Dorozhkin SV (2007) Calcium orthophosphates. J Mater Sci 42(4):1061–1095. https://doi.org/10.1007/s10853-006-1467-8
Le Geros RZ, Le Geros JP (2003) Calcium phosphate bioceramics: past, present and future. Key Eng Mater 3:240–242
Yuan H, Fernandes H, Habibovic P, de Boer J, Barradas AMC, de Ruiter A, Walsh WR, van Blitterswijk CA, de Bruijn JD (2010) Osteoinductive ceramics as a synthetic alternative to autologous bone grafting. Proc Natl Acad Sci U S A 107(31):13614–13619. https://doi.org/10.1073/pnas.1003600107
Davison NL, Luo X, Schoenmaker T, Everts V, Yuan H, Barrère-de Groot F, de Bruijn JD (2014) Submicron-scale surface architecture of tricalcium phosphate directs osteogenesis in vitro and in vivo. Eur Cells Mater 27:281–297
Bohner M (2001) Physical and chemical aspects of calcium phosphates used in spinal surgery. Eur Spine J 10:114–121
Eliaz N, Metoki N (2017) Calcium phosphate bioceramics: a review of their history, structure, properties, coating technologies and biomedical applications. Materials 10(4):104. https://doi.org/10.3390/ma10040334
Daculsi G, Laboux O, Malard O, Weiss P (2003) Current state of the art of biphasic calcium phosphate bioceramics. J Mater Sci Mater Med 14(3):195–200
Kannan S, Goetz-Neunhoeffer F, Neubauer J, Ferreira JMF (2008) Ionic substitutions in biphasic hydroxyapatite and beta-tricalcium phosphate mixtures: structural analysis by rietveld refinement. J Am Ceramic Soc 91(1):1–12. doi:https://doi.org/10.1111/j.1551-2916.2007.02117.x
Kannan S, Lemos AF, Ferreira JMF (2006) Synthesis and mechanical performance of biological-like hydroxyapatites. Chem Mater 18(8):2181–2186
Elliott JC (1994) Structure and chemistry of the apatites and other calcium orthophosphates, vol 18. Studies in inorganic chemistry. Elsevier, London
LeGeros RZ, LeGeros JP, Daculsi G, Kijkowska R (1995) Encyclopedia handbook of biomaterials and bioengineering, vol 2. Marcel Dekker, New York
Monma H, Goto M (1983) Behavior of the α-β phase transformation in tricalcium phosphate. Yohyo-Kyokai-Shi 91:473–475
Yin X, Stott MJ, Rubio A (2003) Phys Rev B - Condens Matter Mater Phys 68:205
Ginebra MP, Traykova T, Planell JA (2006) Calcium phosphate cements as bone drug delivery systems: a review. J Control Release 113(2):102–110
Takahashi Y, Yamamoto M, Tabata Y (2005) Osteogenic differentiation of mesenchymal stem cells in biodegradable sponges composed of gelatin and beta-tricalcium phosphate. Biomater 26:3587–3596
Metzger DS, Driskell TD, Paulsrud JR (1982) Tricalcium phosphate ceramic: a resorbable bone implant: review and current status. J Am Dent Assoc 105:1035–1048
Kanazawa Te (1989) Inorganic phosphate materials. In: Materials science monographs. Tokyo.
Brown PW, Martin R (1999) An analysis of hydroxyapatite surface layer formation. J Phys Chem B 103:1671–1675
Habraken W, Habibovic P, Epple M, Bohner M (2016) Calcium phosphates in biomedical applications: materials for the future? Mater Today 19(2):69–87. doi:https://doi.org/10.1016/j.mattod.2015.10.008
Brown WE, Chow LC (1983) A new calcium-phosphate setting cement. J Dent Res 62:672–672
Ginebra MP, Traykova T, Planell JA (2006) Calcium phosphate cements: competitive drug carriers for the musculoskeletal system? Biomaterials 27(10):2171–2177
Dorozhkin SV (2008) Calcium orthophosphates cements for biomedical application. J Mater Sci: Mater in Med 43:3028–3057
Bohner M (2007) Reactivity of calcium phosphate cements. J Mater Chem 17(38):3980–3986. https://doi.org/10.1039/B706411j
Bohner M, Gbureck U (2008) Thermal reactions of brushite cements. J Biomed Mater Res Part B Appl Biomater 84B(2):375–385. https://doi.org/10.1002/Jbm.B.30881
Barralet JE, Lilley KJ, Grover LM, Farrar DF, Ansell C, Gbureck U (2004) Cements from nanocrystalline hydroxyapatite. J Mater Sci Mater Med 15(4):407–411
Bauer TW, Muschler GF (2000) Bone graft materials. An overview of the basic science. Clin Orthop Relat Res 371:10–27
Pina S, Vieira SI, Torres PMC, Goetz-Neunhoeffer F, Neubauer J, Silva OABdCe, Silva EFdCe, Ferreira JMF (2010) In vitro performance assessment of new brushite-forming Zn- and ZnSr-substituted β-TCP bone cements. J Biomed Mater Res B 94B:414–420
http://biomaterials-org.securec7.ezhostingserver.com/week/bio20.cfm
Dorozhkin SV (2013) Self-setting calcium orthophosphate formulations. J Funct Biomater 4(4):209–311. https://doi.org/10.3390/jfb4040209
Arcos D, Vallet-Regí M (2013) Bioceramics for drug delivery. Acta Mater 61(3):890–911. https://doi.org/10.1016/j.actamat.2012.10.039
Mostaghaci B, Loretz B, Lehr CM (2016) Calcium phosphate system for gene delivery: historical background and emerging opportunities. Curr Pharm Design 22(11):1529–1533. https://doi.org/10.2174/1381612822666151210123859
Shekhar S, Roy A, Hong D, Kumta PN (2016) Nanostructured silicate substituted calcium phosphate (NanoSiCaPs) nanoparticles - efficient calcium phosphate based non-viral gene delivery systems. Mater Sci Eng C Mater Biol Appl 69:486–495. https://doi.org/10.1016/j.msec.2016.06.076
Sherman SL, Thyssen E, Nuelle CW (2017) Osteochondral autologous transplantation. Clin Sports Med 36(3):489–500. https://doi.org/10.1016/J.CSM.2017.02.006
Panseri S, Russo A, Cunha C, Bondi A, Di A, bullet M, Patella S, Kon E (2012) Osteochondral tissue engineering approaches for articular cartilage and subchondral bone regeneration. Knee Surg Sports Traumatol Arthrosc 20:1182–1191. https://doi.org/10.1007/s00167-011-1655-1
Ng A, Bernhard K (2017) Osteochondral autograft and allograft transplantation in the talus. Clin Podiatr Med Surg 34(4):461–469. https://doi.org/10.1016/j.cpm.2017.05.004
Begama H, Nandi SK, Kundu B, Chanda A (2017) Strategies for delivering bone morphogenetic protein for bone healing. Mater Sci Eng C 70:856–869. https://doi.org/10.1016/J.MSEC.2016.09.074
Ogawa K, Miyaji H, Kato A, Kosen Y, Momose T, Yoshida T, Nishida E, Miyata S, Murakami S, Takita H, Fugetsu B, Sugaya T, Kawanami M (2016) Periodontal tissue engineering by nano beta-tricalcium phosphate scaffold and fibroblast growth factor-2 in one-wall infrabony defects of dogs. J Periodont Res 51(6):758–767. https://doi.org/10.1111/jre.12352
Lv YM, Yu QS (2015) Repair of articular osteochondral defects of the knee joint using a composite lamellar scaffold. Bone Jt Res 4(4):56–64. https://doi.org/10.1302/2046-3758.44
Xue D, Zheng Q, Zong C, Li Q, Li H, Qian S, Zhang B, Yu L, Pan Z (2010) Osteochondral repair using porous poly(lactide-co-glycolide)/nano-hydroxyapatite hybrid scaffolds with undifferentiated mesenchymal stem cells in a rat model. J Biomed Mater Res A 94(1):259–270. https://doi.org/10.1002/jbm.a.32691
Oliveira JM, Silva SS, Malafaya PB, Rodrigues MT, Kotobuki N, Hirose M, Gomes ME, Mano JF, Ohgushi H, Reis RL (2009) Macroporous hydroxyapatite scaffolds for bone tissue engineering applications: physicochemical characterization and assessment of rat bone marrow stromal cell viability. J Biomed Mater Res A 91A(1):175–186. https://doi.org/10.1002/jbm.a.32213
Żylińska B, Stodolak-Zych E, Sobczyńska-Rak A, Szponder T, Silmanowicz P, Łańcut M, Jarosz Ł, Różański P, Polkowska I (2017) Osteochondral repair using porous three-dimensional Nanocomposite scaffolds in a rabbit model. In Vivo 31(5):895–903
Li J, Kim K, Roohani-Esfahani S, Guo J, Kaplan D, Zreiqat H (2015) A biphasic scaffold based on silk and bioactive ceramic with stratified properties for osteochondral tissue regeneration. J Mater Chem B Mater Biol Med. 3(26): 5361–5376
Guo X, Wang C, Duan C, Descamps M, Zhao Q, Dong L, Lu S, Anselme K, Lu J, Song YQ, Lü S, Anselme K, Lu J, Song YQ (2004) Repair of osteochondral defects with autologous chondrocytes seeded onto bioceramic scaffold in sheep. Tissue Eng 10(11–12):1830–1840. https://doi.org/10.1089/ten.2004.10.1830
Bian W, Li D, Lian Q, Li X, Zhang W, Wang K, Jin Z (2012) Fabrication of a bio-inspired beta-Tricalcium phosphate/collagen scaffold based on ceramic stereolithography and gel casting for osteochondral tissue engineering. Rapid Prototyp J 18(1):68–80. https://doi.org/10.1108/13552541211193511
Unther Heimke G, Leyen S, Willmann G (2002) Knee arthoplasty: recently developed ceramics offer new solutions. Biomaterials 23:1539–1551
Pina S, Vieira SI, Rego P, Torres PMC, da Cruz e Silva OAB, da Cruz e Silva EF, ferreira JMF (2010) Biological responses of brushite-forming Zn- and ZnSr substituted β-tricalcium phosphate bone cements. Eur Cells Mater 20:162–177. doi:https://doi.org/10.22203/eCM.v020a14
Flautre B, Maynou C, Lemaitre J, Van Landuyt P, Hardouin P (2002) Bone colonization of B-TCP granules incorporated in brushite cements. J Biomed Mater Res 63(4):413–417. https://doi.org/10.1002/jbm.10262
Gotterbarm T, Richter W, Jung M, Berardi Vilei S, Mainil-Varlet P, Yamashita T, Breusch SJ (2006) An in vivo study of a growth-factor enhanced, cell free, two-layered collagen-tricalcium phosphate in deep osteochondral defects. Biomaterials 27(18):3387–3395. https://doi.org/10.1016/j.biomaterials.2006.01.041
Malafaya PB, Reis RL (2009) Bilayered chitosan-based scaffolds for osteochondral tissue engineering: influence of hydroxyapatite on in vitro cytotoxicity and dynamic bioactivity studies in a specific double-chamber bioreactor. Acta Biomater 5(2):644–660. https://doi.org/10.1016/j.actbio.2008.09.017
Fiedler BA, Ferguson M (2017) Overview of medical device clinical trials. In. Elsevier, pp 17–32. doi:https://doi.org/10.1016/B978-0-12-804179-6.00002-2
Acknowledgments
The authors acknowledge the project FROnTHERA (NORTE-01-0145-FEDER-000023), supported by Norte Portugal Regional Operational Programme (NORTE 2020), under the PORTUGAL 2020 Partnership Agreement, through the European Regional Development Fund (ERDF). Also, H2020-MSCA-RISE program, as this work is part of developments carried out in BAMOS project, funded from the European Union’s Horizon 2020 research and innovation program under grant agreement N° 734156. The financial support from the Portuguese Foundation for Science and Technology for the funds provided under the program Investigador FCT 2012, 2014, and 2015 (IF/00423/2012, IF/01214/2014, and IF/01285/2015) is also greatly acknowledged.
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Pina, S., Rebelo, R., Correlo, V.M., Oliveira, J.M., Reis, R.L. (2018). Bioceramics for Osteochondral Tissue Engineering and Regeneration. In: Oliveira, J., Pina, S., Reis, R., San Roman, J. (eds) Osteochondral Tissue Engineering. Advances in Experimental Medicine and Biology, vol 1058. Springer, Cham. https://doi.org/10.1007/978-3-319-76711-6_3
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