Structure Of Natural Bone Research Articles

Selective Voronoi tessellation as a method to design anisotropic and biomimetic implants

The geometry of a metallic scaffold is important for the success of bone implants, where the introduction of porosity can reduce stress shielding effects and allow for bone tissue integration. In this work, porous scaffolds were designed to closely mimic the natural structure of trabecular bone using selective Voronoi tessellation with preferential seeding. A workflow to generate these structures is introduced, where voided regions of seeds in the starting volume create preferential texture during polyhedral expansion, resulting in modified strut orientation in the implant. Anisotropy was digitally characterized by mean-intercept length and star volume distribution measurements to determine similarity to trabecular orientation. This work demonstrates that selective Voronoi tessellation is an effective method to generate biomimetic porous scaffolds with increased anisotropy and tunable strut architecture in three dimensions as a suitable alternative to patient-derived bone geometries.

ADVANCED NANOMATERIALS AND COATED SURFACES FOR ORTHOPEDIC IMPLANTS – A REVIEW

Critical-sized defects in bone induced by trauma have in numerous presented cases difficult challenges to the current treatment for bone repair. The main purpose of bone tissue engineered scaffolds is to use advanced materials to promote the natural healing process of bone which does not easily occur in critical-sized defects or on metallic implants. A synthetic bone scaffold and a coating on Ti implants must be biocompatible and biodegradable to allow the native tissue integration, and mimic the chemical composition and structure of native bone. In addition to being physically and chemically biomimetic, an ideal scaffold and the coating layers on metallic implants must be capable of releasing essential physiologic elements, like Mg, Zn, Sr and Si, and also containing bioactive molecules (e.g., collagen, COL) to accelerate extracellular matrix production and tissue integration. Also, these advanced materials might be doped with drugs (e.g., antibiotics, such as vancomycin) to prevent undesired biological response such as infections, especially with Staphylococcus aureus, S. aureus. Various biomaterials include hydroxyapatite (HAP) ceramics or multifunctional hydroxyapatite substituted with Mg, Zn, Sr and Si, mf-HAP, polymers, such as poly lactic acid (PLA, approved for medical applications by Food and Drug Administration, US FDA, and collagen, or their mixtures as biomimetic composites which have been investigated for their potential as bone scaffold materials and coatings on metallic implants. This article briefly reviews the physical and chemical characteristics of used advanced materials and describes the key-technologies in mimicking the physical and chemical environment of bone using synthetic materials, and provides an over view of local drug delivery as it pertains to bone tissue engineering.

Biological evaluation of the modified nano-amorphous phosphate calcium doped with citrate/poly-amino acid composite as a potential candidate for bone repair and reconstruction

Large numbers of research works related to fabricating organic–inorganic composite materials have been carried out to mimic the natural structure of bone. In this study, a new modified n-ACP doped with citrate (n-ACP-cit)/poly (amino acids) (PAA) composite (n-ACP-cit/PAA) was synthesized by employing high bioactive n-ACP-cit and the biodegradable and biocompatible PAA copolymer. Its basic structure was characterized by X-ray diffraction spectroscopy, Fourier transformed infrared spectroscopy, and X-ray photoelectron spectroscopy. Moreover, the degradability, bioactivity, biocompatibility, and osteoconductivity of n-ACP-cit/PAA composite were evaluated in vitro and in vivo, using simulated body fluid (SBF) solution soaking test, mouse bone marrow mesenchymal stem cells proliferation and differentiation, morphological observation test, expression of genes associated with osteogenesis, and bone defect model repair test, respectively. The modified n-ACP-cit/PAA composite exhibited a much higher weight loss rate (36.01 wt.%) than that of PAA (23.99 wt.%) after immersing in SBF solution for 16 weeks and the pH values of local environment restored to neutral condition. Moreover, cells co-culturing with composites exhibited higher alkaline phosphatase activity, more calcium nodule-formation, and higher expression levels of osteogenic differentiation-related genes (Bmp-2, Colla I, OCN, OPN, and Runx-2) than that of PAA. Furthermore, the bone defect model repair test revealed that the composite could be intimately incorporated with the surrounding bone without causing any deleterious reaction and capable of guiding new bone formation. Together, these results indicated that the new modified bone repair n-ACP-cit/PAA composite material with specific characteristics may be designed for meeting diverse requirements from biomedical applications.

Modulated Composite Nanofibers with Enhanced Structural Stability for Promotion of Hard Tissue Healing

While various polyesters have been electrospun into fibrous scaffolds, these constructs lack sufficient strength and osteoconductivity that is usually desired for potential bone tissue engineering. Here, hydroxyapatite (HA), either in the form of traditional nanospheres or in the form of nanorods, was tried to incorporate into a new nanofibrous scaffold based on electrospun poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) with a given 3-hydroxyvalerate (HV) content. The rod-like nanoparticles were used, in particular, to closely mimic the natural structure of bone. Since the solubility of polymers is a critical parameter in the electrospinning process, the solubility of PHBV having different HV contents was also examined in different solvents using a combined experimental and theoretical study. According to the results, 1,1,1,3,3,3-hexafluoropropan-2-ol is ideally able to dissolve PHBV with 5% HV content and hence to produce nanofibers with minimal structural defects during the electrospinning process. Moreover, although both the spherical and rod-like particles could be homogeneously embedded in the PHBV at the expected concentration, the addition of rod-like HA to PHBV can result in composite nanofibers with a significantly enhanced structural strength.

Construction of Zn-incorporated Micro/Nano Hierarchical Structure Coatings on Tantalum

Tantalum (Ta) alloys have been widely used as bone repair materials due to their excellent biocompatibility. In present work, zinc (Zn) incorporated ceramic coatings with micro/nano hierarchical structure were successfully fabricated on Ta by micro-arc oxidation and hydrothermal treatment. The content of Zn ions is about (1.35 ± 0.3) wt%. Cortex-like rough morphology (Ra: 1.504 µm) with irregular vermiform slots can be clearly observed on the surface of Ta. More importantly, the coatings resembling the structure of natural bone can release Zn, Ca, and P ions in a controlled and sustained manner. The corrosion resistance of Ta is greatly improved after functionalized with ceramic coatings, confirming by potentiodynamic polarization tests. The bonding strength between the coatings and substrates can be up to 18.9 N. Furthermore, the surface of MAOs-HT@Ta is covered by bonelike apatite after immersed in Simulated Body Fluid (SBF) for three weeks, showing excellently bioactivity. These results suggest that the innovative Zn-incorporated micro/nano hierarchical coatings on Ta may be used as promising candidates for orthopedic implants.

Study on the properties of PLA/PBAT composite modified by nanohydroxyapatite

Poly(lactic acid) (PLA) and poly(butylene adipate-Co-terephthalate) (PBAT) show high and excellent biocompatibility, which are promising materials used in bone tissue engineering field. In this research, n-HA/PLA/PBAT/MCC composites were prepared by solution blending method. Nano hydroxyapatite (n-HA) was used as nucleation, and microcrystalline cellulose (MCC) was added to improve the degradation performance of the materials. Compared with the composite without n-HA, the crystallinity of the composites with 6% n-HA was increased by 62%. The scanning electron microscopy (SEM) and the transmission electron microscopy (TEM) showed that the n-HA was evenly dispersed in the composites when the addition ration of n-HA was lower than 6%, while obvious agglomeration of n-HA appeared at the addition ratio of 10%. The tensile test demonstrated that the tensile strength of the composites with different addition ratio transcended the needs of bone tissue engineering materials. The introduction of n-HA in obtained composites simulated the composition and structure of native bone, which suggested a potential utility and application prospect in bone tissue engineering.

Lithography-Based 3D Bioprinting and Bioinks for Bone Repair and Regeneration.

The fabrication of scaffolds that precisely mimic the natural structure and physiochemical properties of bone is still one of the most challenging tasks in bone tissue engineering. 3D printing techniques have drawn increasing attention due to their ability to fabricate scaffolds with complex structures and multiple bioinks. For bone tissue engineering, lithography-based 3D bioprinting is frequently utilized due to its printing speed, mild printing process, and cost-effective benefits. In this review, lithography-based 3D bioprinting technologies including SLA and DLP are introduced; their typical applications in biological system and bioinks are also explored and summarized. Furthermore, we discussed possible evolution of the hardware/software systems and bioinks of lithography-based 3D bioprinting, as well as their future applications.

Finite element analysis of gradient lattice structure patterns for bone implant design

PurposeThe objective of this paper is to identify suitable lattice structure patterns for the design of porous bone implants manufactured using additive manufacturing.Design/methodology/approachThe study serves to compare and analyse the mechanical behaviours between cubic and octet-truss gradient lattice structures. The method used was uniaxial compression simulations using finite element analysis to identify the translational displacements.FindingsFrom the simulation results, in comparison to the cubic lattice structure, the octet-truss lattice structure showed a significant difference in mechanical behaviour. In the same design space, the translational displacement for both lattice structures increased as the relative density decreased. Apart from the relative density, the microarchitecture of the lattice structure also influenced the mechanical behaviour of the gradient lattice structure.Research limitations/implicationsGradient lattice structures are suitable for bone implant applications because of the variation of pore sizes that mimic the natural bone structures. The complex geometry that gradient lattice structures possess can be manufactured using additive manufacturing technology.Originality/valueThe results demonstrated that the cubic gradient lattice structure has the best mechanical behaviour for bone implants with appropriate relative density and pore size.

Ultrafast bone-like apatite formation on highly porous poly(l-lactic acid)-hydroxyapatite fibres.

In order to provide a favourable environment for living bone formation, it is an essential condition to grow bone-like apatite layer at the interface between the tissue-implant and its surrounding tissues. Inspired by the chemical composition and the nano porous structure of natural bones, we developed an ultrafast and accessible route to accelerate effectively the formation of bone-like apatite on the surface of porous poly(l-lactic acid)-hydroxyapatite (PLLA-HA) composite fibres in 5 times simulated body fluid (5SBF). The key of the method lays in successful exposure of HA nanoparticles on the surface of PLLA fibres by acetone treatment of electrospun PLLA-HA nano/micro fibres. The recrystallization of PLLA chains uncovers more HA nanoparticles on the surface of every fibre which provide nucleation sites for calcium and phosphate ions. After only 2h of immersing in 5SBF, a full layer of apatite completely covered on the surface of porous PLLA-HA fibres. The results indicate that HA nanoparticles on porous fibre surface can accelerate the kinetic deposition of apatite on fibre surface. Biological in vitro cell culture with human osteoblast-like cell for up to 7days demonstrates that the incorporation of HA nanoparticles on the surface of porous PLLA fibrous membranes leads to significant enhance osteoblast adhesion and proliferation. The route can open avenues for development of fibrous PLLA biomaterials for hard tissue repair and substitution.

Biodegradable 3D printed HA/CMCS/PDA scaffold for repairing lacunar bone defect.

Three-dimensional (3D) printing technology has attracted considerable focus for preparing porous bone repair scaffolds to promote bone regeneration. Inspired by organic-inorganic components and the porous structure of natural bone, novel porous degradable scaffolds have been printed using hydroxyapatite (HA), carboxymethyl chitosan (CMCS), and polydopamine (PDA). The well-designed HA/CMCS/PDA scaffolds exhibited a porous structure with 60.5±4.6% porosity and 415±87μm in mode pore diameter. The weight loss percentage (WL%) of the HA/CMCS/PDA scaffolds reached about 17% during a 10-week degradation in vitro. The degradation process between the CMCS and HA induced the release of calcium ions. Using commercial product as the contrast material, the osteogenic properties of the scaffolds were assessed in vivo. The implantation and degradation of HA/CMCS/PDA scaffolds had no adverse effects on the kidney and liver of rabbits with no inflammatory response in the implantation sites. The micro-CT and histology data suggested that the HA/CMCS/PDA scaffolds could effectively stimulate new bone formation within the femoral lacuna defect region of rabbits versus blank control at 12weeks after implantation. Surface cortical bone was generated in the defect area in the HA/CMCS/PDA group; the defect in the blank group remained obvious. HA/CMCS/PDA scaffolds had excellent biodegradability matching the formation of new bone during implantation. In conclusion, 3D-printed HA/CMCS/PDA scaffolds have remarkable potential as a new material for repairing bone defects.

Citrate‐Based Tannin‐Bridged Bone Composites for Lumbar Fusion

AbstractConventional bone composites consistently fail to mimic the chemical composition and integrated organic/inorganic structure of natural bone, lacking sufficient mechanics as well as inherent osteoconductivity and osteoinductivity. Through a facile surface coating process, the strong adhesive, tannic acid (TA), is adhered to the surface of the natural bone component, hydroxyapatite (HA), with and without the immobilization of in situ formed silver nanoparticles. Residual functional groups available on the immobilized TA substituents are subsequently covalently linked to the citrate‐based biodegradable polymer, poly(octamethylene citrate) (POC), effectively bridging the organic and inorganic phases. Due to the synergistic effects of the tannin and citrate components, the obtained citrate‐based tannin‐bridged bone composites (CTBCs) exhibit vastly improved compression strengths up to 323.0 ± 21.3 MPa compared to 229.9 ± 15.6 MPa for POC‐HA, and possess tunable degradation profiles, enhanced biomineralization performance, favorable biocompatibility, increased cell adhesion and proliferation, as well as considerable antimicrobial activity. In vivo study of porous CTBCs using a lumbar fusion model further confirms CTBCs' osteoconductivity and osteoinductivity, promoting bone regeneration. CTBCs possess great potential for bone regeneration applications while the immobilized TA additionally preserves surface bioconjugation sites to further tailor the bioactivity of CTBCs.

Cellulose nanocrystals reinforced gelatin/bioactive glass nanocomposite scaffolds for potential application in bone regeneration

Simulating components, precise porous three-dimensional structure and physico-mechanical properties of natural bone have become a vital direction in the development of bone tissue regeneration. This work focused on enhancing mechanical strength of scaffold materials for bone regeneration, a subject of serious attention in its fabrication. Hence, cellulose nanocrystals (CNC), possessing favorable biocompatibility and impressive mechanical properties, was selected to reinforce the nanocomposite scaffolds of gelatin/bioactive glass (BG-Gel) system. The porous composite BG-Gel-CNC was simultaneously constructed by in-situ composite method and freeze-drying technique. The results manifested that the scaffolds incorporated with CNC showed a desirable compressive strength compared to the control, better wettability, which is conducive to better adhesion, growth and proliferation of cells. In addition, appropriate porosity, pore connectivity and biocompatibility were also demonstrated. These findings therefore suggested their potential application to function as effective scaffold materials in bone tissue regeneration.

Osteo-Compatibility of 3D Titanium Porous Coating Applied by Direct Energy Deposition (DED) for a Cementless Total Knee Arthroplasty Implant: in Vitro and in Vivo Study.

Direct energy deposition (DED) technology has gained increasing attention as a new implant surface technology that replicates the porous structure of natural bones facilitating osteoblast colonization and bone ingrowth. However, concerns have arisen over osteolysis or chronic inflammation that could be caused by Cobalt-chrome (CoCr) alloy and Titanium (Ti) nanoparticles produced during the fabrication process. Here, we evaluated whether a DED Ti-coated on CoCr alloy could improve osteoblast colonization and osseointegration in vitro and in vivo without causing any significant side effects. Three types of implant CoCr surfaces (smooth, sand-blasted and DED Ti-coated) were tested and compared. Three cell proliferation markers and six inflammatory cytokine markers were measured using SaOS2 osteoblast cells. Subsequently, X-ray and bone histomorphometric analyses were performed after implantation into rabbit femur. There were no differences between the DED group and positive control in cytokine assays. However, in the 5-bromo-2′-deoxyuridine (BrdU) assay the DED group exhibited even higher values than the positive control. For bone histomorphometry, DED was significantly superior within the 1000 µm bone area. The results suggest that DED Ti-coated metal printing does not affect the osteoblast viability or impair osseointegration in vitro and in vivo. Thus, this technology is biocompatible for coating the surfaces of cementless total knee arthroplasty (TKA) implants.

Bone regeneration with hydroxyapatite-based biomaterials

Degeneration, trauma, and tumor resection are the main causes of bone loss (Owen et al., J. Biomed. Mater. Res. B Appl. Biomater. 106(6), 2493-2512 (2018), Korkusuz et al., (2014), Kondo et al., Biomaterials. 26, 5600-5608 (2005), Matsumine et al., J. Bone Joint Surg. [Br]. 86-B, 5 (2004), Christensen et al., Knee Surg. Sports Traumatol. Arthrosc. 24, 2380-2387 (2016), Calabrese et al. Scientific Reports. 7(1), 1-11 (2017); Korkusuz et al. (2017), Morimoto et al. Spine J. 15, 1379-1390 (2015); Tang et al. Biomaterials 83, 363-382 (2016)). Autografts are still considered as the golden standard for bone regeneration. Donor site shortage, prolonged surgery time, blood loss, and donor site morbidity are the main drawbacks. Allografts are osteoconductive and to an extent osteoinductive. But they have low osteogenicity, possible immunologic reactions, and low mechanical strength and are associated with ethical or religious concerns. In order to overcome these disadvantages, studies on composites with ideal ranges of porosity, biodegradation rate, bioactivity, osteoinductivity, osteoconductivity, and mechanical properties are a popular research area.Calcium phosphate ceramics (CPCs) are biodegradable, biocompatible, and bioactive materials. Their resemblance to the inorganic part of bone makes them good alternatives to autografts and allografts (Korkusuz et al. (2014), Jeong et al. Biomaterials Research 23, 4 (2019), Rouahi et al., Colloids Surf. B: Biointerf. 47(1), 10-19 (2006)). Throughout CPCs, β-tricalcium phosphate (β-TCP), biphasic calcium phosphates (BCPs), and hydroxyapatite (HA) are frequently used in regeneration studies. Hydroxyapatite [Ca10(PO4)6(OH)2] is the main inorganic component of bones (~ 70% of bone tissue). HA is combined with many different natural or synthetic polymers and/or growth factors/cells to imitate the natural structure of bone in order to achieve bone formation and regeneration by either enhancing its osteoconductivity, osteoinductivity, or both. Nanohydroxyapatite (nHA) has a smaller grain size, and therefore, the increased surface area allows more cells and proteins to adhere on the surface. This therefore increases the ideal properties of a bone substitute. Here in this review, the use of HA in bone regeneration is briefly summarized.

Polysaccharide-Based Systems for Targeted Stem Cell Differentiation and Bone Regeneration.

Bone tissue engineering is an ever-changing, rapidly evolving, and highly interdisciplinary field of study, where scientists try to mimic natural bone structure as closely as possible in order to facilitate bone healing. New insights from cell biology, specifically from mesenchymal stem cell differentiation and signaling, lead to new approaches in bone regeneration. Novel scaffold and drug release materials based on polysaccharides gain increasing attention due to their wide availability and good biocompatibility to be used as hydrogels and/or hybrid components for drug release and tissue engineering. This article reviews the current state of the art, recent developments, and future perspectives in polysaccharide-based systems used for bone regeneration.

Electrophoretic deposition of collagen-reinforced HA/CTS biocomposite coatings

In this study, the biomimetic approach described as reverse engineering by trying to copy the excellent concepts of nature and taking nature as a model has been used. In order to mimic the structure of natural bone, hydroxyapatite (HA), chitosan (CTS) and collagen have been combined as a novel type of biocomposite coating. HA/CTS/collagen biocomposite coatings have been successfully electrophoretically deposited on Ti6Al4V biomedical implants. A novel type of a polyelectrolyte consisting of ethanol, water and isopropyl alcohol has been used for the electrophoretic deposition process. The effect of collagen concentration on the structural and corrosion protection performance of the biocomposite coatings has been investigated by X-ray diffraction, field-emission scanning electron microscopy, Fourier transform infrared spectroscopy, potentiodynamic polarization (Tafel extrapolation) and electrochemical impedance spectroscopy techniques. The electrophoretically deposited HA/CTS/collagen biocomposite coatings have exhibited corrosion protection against simulated physiological body fluid up to five times better than that of bare Ti6Al4V alloy.

Retraction Note to: Mechanical and Bioactivity Assessment of Wollastonite/PVA Composite Synthesized from Bentonite Clay

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Bone-Inspired Mineralization with Highly Aligned Cellulose Nanofibers as Template.

Bioinspired by the aligned structure and building blocks of bone, this work mineralized the aligned bacterial cellulose (BC) through in situ mineralization using CaCl2 and K2HPO4 solutions. The cellulose nanofibers were aligned by a scalable stretching process. The aligned and mineralized bacterial cellulose (AMBC) homogeneously incorporated hydroxyapatite (HAP) with a high mineral content and exhibited excellent mechanical strength. The ordered 3D structure allowed the AMBC composite to achieve a high elastic modulus and hardness and the development of a nanostructure inspired by natural bone. The AMBC composite exhibited an elastic modulus of 10.91 ± 3.26 GPa and hardness of 0.37 ± 0.18 GPa. Compared with the nonaligned mineralized bacterial cellulose (NMBC) composite with mineralized crystals of HAP randomly distributed into the BC scaffolds, the AMBC composite possessed a 210% higher elastic modulus and 95% higher hardness. The obtained AMBC composite had excellent mechanical properties by mimicking the natural structure of bone, which indicated that the organic BC aerogel with aligned nanofibers was a promising template for biomimetic mineralization.

Applications of Carbon Nanotubes in Bone Tissue Regeneration and Engineering: Superiority, Concerns, Current Advancements, and Prospects.

With advances in bone tissue regeneration and engineering technology, various biomaterials as artificial bone substitutes have been widely developed and innovated for the treatment of bone defects or diseases. However, there are no available natural and synthetic biomaterials replicating the natural bone structure and properties under physiological conditions. The characteristic properties of carbon nanotubes (CNTs) make them an ideal candidate for developing innovative biomimetic materials in the bone biomedical field. Indeed, CNT-based materials and their composites possess the promising potential to revolutionize the design and integration of bone scaffolds or implants, as well as drug therapeutic systems. This review summarizes the unique physicochemical and biomedical properties of CNTs as structural biomaterials and reinforcing agents for bone repair as well as provides coverage of recent concerns and advancements in CNT-based materials and composites for bone tissue regeneration and engineering. Moreover, this review discusses the research progress in the design and development of novel CNT-based delivery systems in the field of bone tissue engineering.

Lamellar structure/processing relationships and compressive properties of porous Ti6Al4V alloys fabricated by freeze casting

Lamellar pores have superior biocompatibility due to their similarity to the lamellar structure of natural bones. In the present work, porous Ti6Al4V alloys with lamellar pores were successfully fabricated by directionally freeze casting. The lamellar structure/processing relationships were systematically studied through analyzing the interaction between ice front and alloy powders. The structural feature of translamella bridges is observed in the lamellar structure. The volume shrinkage of porous Ti6Al4V alloys is in the range of 44-60%. This is much higher compared with that of the porous ceramics. The solid content in the slurry exerts a strong influence on the porosity, while the freezing ice front velocity affects the structural wavelength and pore width. With the increase in ice front velocity, the structural wavelength decreases by an exponential function. The lamella formation mechanism and porosity gradient along the freezing direction were discussed. Young's modulus and yield stress of porous Ti6Al4V alloys fall in the range of 2-12 GPa and 40-300 MPa, respectively. The dominant compressive deformation mode is lamella buckling and splitting. The fabricated porous Ti6Al4V alloys possess higher relative yield stress.