Silicate Bioactive Glass Research Articles

Titania effect on the bioactivity of silicate bioactive glasses

This study reports about the influence of titania on the structure and bioactivity of 60SiO2 ⋅ (32 − x)CaO · 8P2O5 · xTiO2 glasses with 0 ≤ x ≤ 12 mol%. In order to analyse the evolution of the apatite structure self‐assembled on the glass surface after immersion in simulated body fluid, a complementary approach of different techniques was applied such as X‐ray diffraction, Fourier transform infrared spectroscopy (FT‐IR), scanning electron microscopy and Raman spectroscopy. It was evidenced that the crystalline hydroxyapatite amount and the size of the nanostructured apatite phase, i.e. crystalline and amorphous one, decrease with the rise of TiO2 content. FT‐IR spectra recorded in reflection mode showed the increase of the apatite‐like structure amount as the titania content became higher. On the other hand, the behaviour of the full width at half maximum of the most intense Raman signal originating from the apatite‐like structure confirms the size decrease of the nanostructured apatite phase with the progressive addition of TiO2 and shows the existence of a less ordered apatite‐like structure. The herein presented investigation demonstrates that the FWHM of the Raman signal combined with the FT‐IR data recorded in reflection mode can be used as key spectral indicators for elucidating the evolution of apatite‐like structures developed on the bioactive material surface. Copyright © 2016 John Wiley & Sons, Ltd.

Effect of copper-doped silicate 13–93 bioactive glass scaffolds on the response of MC3T3-E1 cells in vitro and on bone regeneration and angiogenesis in rat calvarial defects in vivo

The release of inorganic ions from biomaterials could provide an alternative approach to the use of growth factors for improving tissue healing. In the present study, the release of copper (Cu) ions from bioactive silicate (13–93) glass scaffolds on the response of cells in vitro and on bone regeneration and angiogenesis in vivo was studied. Scaffolds doped with varying concentrations of Cu (0–2.0wt.% CuO) were created with a grid-like microstructure by robotic deposition. When immersed in simulated body fluid in vitro, the Cu-doped scaffolds released Cu ions into the medium in a dose-dependent manner and converted partially to hydroxyapatite. The proliferation and alkaline phosphatase activity of pre-osteoblastic MC3T3-E1 cells cultured on the scaffolds were not affected by 0.4 and 0.8wt.% CuO in the glass but they were significantly reduced by 2.0wt.% CuO. The percent new bone that infiltrated the scaffolds implanted for 6weeks in rat calvarial defects (46±8%) was not significantly affected by 0.4 or 0.8wt.% CuO in the glass whereas it was significantly inhibited (0.8±0.7%) in the scaffolds doped with 2.0wt.% CuO. The area of new blood vessels in the fibrous tissue that infiltrated the scaffolds increased with CuO content of the glass and was significantly higher for the scaffolds doped with 2.0wt.% CuO. Loading the scaffolds with bone morphogenetic protein-2 (1μg/defect) significantly enhanced bone infiltration and reduced fibrous tissue in the scaffolds. These results showed that doping the 13–93 glass scaffolds with up to 0.8wt.% CuO did not affect their biocompatibility whereas 2.0wt.% CuO was toxic to cells and detrimental to bone regeneration.

Modification of resin modified glass ionomer cement by addition of bioactive glass nanoparticles.

In the present study, sol-gel derived nanoparticle calcium silicate bioactive glass was added to the resin-modified light cure glass-ionomer cement to assess the influence of additional bioactive glass nanoparticles on the mechanical and biological properties of resin-modified glass-ionomer cement. The fabricated bioactive glass nanoparticles added resin-modified glass-ionomer cements (GICs) were immersed in the phosphate buffer solution for 28 days to mimic real condition for the mechanical properties. Resin-modified GICs containing 3, 5 and 10 % bioactive glass nanoparticles improved the flexural strength compared to the resin-modified glass-ionomer cement and the samples containing 15 and 20 % bioactive glass nanoparticles before and after immersing in the phosphate buffer solution. Characterization of the samples successfully expressed the cause of the critical condition for mechanical properties. Cell study clarified that resin-modified glass-ionomer cement with high concentrations of bioactive glass nanoparticles has higher cell viability and better cell morphology compare to control groups. The results for mechanical properties and toxicity approved that the considering in selection of an optimum condition would have been a more satisfying conclusion for this study.

Structure optimisation and biological evaluation of bone scaffolds prepared by co-sintering of silicate and phosphate glasses

A degradable phosphate glass (ICEL) and a bioactive silicate glass (CEL2) were mixed in different ratios (wt-%: 100%ICEL, 70%ICEL–30%CEL2, 30%ICEL–70%CEL2, 100%CEL2; codes 100-0, 70-30, 30-70, 0-100) and then co-sintered to obtain three-dimensional porous scaffolds by gel casting foaming. Thermal analyses were carried out on the glass mixtures and were used as a starting point for the optimisation of the scaffold sintering treatment. The microcomputed tomography and field emission scanning electron microscope analyses allowed the selection of the optimal sintering temperature to obtain an adequate structure in terms of total and open porosity. The scaffolds showed an increasing solubility with increasing ICEL glass content, and for 30-70 and 0-100, the precipitation of hydroxyapatite in simulated body fluid was observed. In vitro tests indicated that all the scaffolds showed no cytotoxic effect. The co-sintering of silicate and phosphate glasses showed to be a promising strategy to tailor the scaffold osteoconductivity, degradation and bioactivity.

Sol–gel hybrid coatings with strontium-doped 45S5 glass particles for enhancing the performance of stainless steel implants: Electrochemical, bioactive and in vivo response

The protection of stainless-steel implants by applying a hybrid organic–inorganic coating generates a barrier for ion migration and a potential holder for functional particles. Chemical composition of bioactive silicate-glasses (BG) can be varied to tailor their rate of dissolution in the biological environment. The substitution of calcium by strontium (Sr) generates a locally-controlled release of Sr-ions to the media. Strontium is known to reduce bone resorption and stimulate bone formation.This work presents coatings made by sol–gel method containing tetraethoxysilane, methyl-triethoxysilane and silica nanoparticles as precursors, and functionalized either with BG or Sr-substituted BG particles onto surgical grade stainless steel. The coated implants were tested in vitro for corrosion resistance and bioactivity, and in vivo to analyze bone formation.The applied coating system provided an excellent protection to aggressive fluids, even after 30days of immersion. The presence of hydroxyapatite is shown as a first evidence of bioactivity. The evaluation of in vivo tests in Wistar–Hokkaido rat femur 4 or 8weeks after the implantation showed slight differences in the thickness of newly formed bone measured by ESEM, and remarkable changes in bone quality characterized with Raman microscopy. The in vivo response of the coatings containing Sr-substituted bioglass is better at early times of implantation as regards the bone morphology and quality making this functionalized coatings a very promising option for implant protection and bone regeneration.

Development and characterization of lithium-releasing silicate bioactive glasses and their scaffolds for bone repair

Incorporation of therapeutic ions into the structure of bioactive glasses for direct stimulation of cells is a very attractive approach for tissue engineering strategies. Lithium has recently been identified as a biologically active ion which can stimulate osteoblast cell activity. In this study, lithium-containing bioactive glasses (Li-BGs) where Li2O substitutes Na2O in different amounts (2.5, 5 and 10wt.% Li2O) in 45S5 bioactive glass (BG) were produced and made into 3D scaffolds by the foam replica method. The structural changes that occur after heat treatment, the effect of lithium-content on the bioactivity of the glasses and their lithium ion release profiles were investigated. The results show that the novel Li-BG formulations exhibit the formation of an apatite-like layer on their surface after immersion in SBF for 1day thus confirming their high surface reactivity, similar to undoped 45S5 BG. XRD results showed that the Li-doped BGs crystallize mainly to combeite (Na2Ca2Si3O9) and silicorhenanite (SiO4(PO4)2Ca5) but also Li6P6O18 and Li3PO4 phases were detected. In terms of lithium ion release, the formulations at 2.5wt.% and 5wt.% Li2O content were the only ones to be within the therapeutic range (<8.3ppm).

Sol–gel synthesis and in vitro bioactivity of copper and zinc-doped silicate bioactive glasses and glass-ceramics

Metal doping of bioactive glasses based on ternary 60SiO2–36CaO–4P2O5 (58S) and quaternary 60SiO2–25CaO–11Na2O–4P2O5 (NaBG) mol% compositions synthesized using a sol–gel process was analyzed. In particular, the effect of incorporating 1, 5 and 10 mol% of CuO and ZnO (replacing equivalent quantities of CaO) on the texture, in vitro bioactivity, and cytocompatibility of these materials was evaluated. Our results showed that the addition of metal ions can modulate the textural property of the matrix and its crystal structure. Regarding the bioactivity, after soaking in simulated body fluid (SBF) undoped 58S and NaBG glasses developed an apatite surface layer that was reduced in the doped glasses depending on the type of metal and its concentration with Zn displaying the largest inhibitions. Both the ion release from samples and the ion adsorption from the medium depended on the type of matrix with 58S glasses showing the highest values. Pure NaBG glass was more cytocompatible to osteoblast-like cells (SaOS-2) than pure 58S glass as tested by 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. The incorporation of metal ions decreased the cytocompatibility of the glasses depending on their concentration and on the glass matrix doped. Our results show that by changing the glass composition and by adding Cu or Zn, bioactive materials with different textures, bioactivity and cytocompatibility can be synthesized.

Novel Highly Degradable Chloride Containing Bioactive Glasses

AbstractAddition of CaF2 to a silicate bioactive glass favours formation of fluorapatite, which is less soluble in acidic environment than hydroxyapatite. However, excess CaF2 in the glass is problematic, owing to the formation of crystalline calcium fluoride rather than fluorapatite on immersion. In this paper we investigate chloride as an alternative to fluoride in bioactive silicate glasses and in particular their bioactivity for the first time. Meltderived bioactive glasses based on SiO2-P2O5-CaO-CaCl2 with varying CaCl2 contents were synthesised and characterised by DSC. Chemical analysis of the chloride content was performed by using an ion selective electrode. Glass density was determined using Helium Pycnometry. The glass bioactivity was investigated in Tris buffer. Ion release measurements were carried out by using ICP-OES. The chemical analysis results indicated that the majority of the chloride is retained in the Q2 type silicate glasses during synthesis. Tg and glass density reduced with increasing CaCl2 content. Apatite-like phase formation was confirmed by FITR, XRD and 31P MAS-NMR. The results of the in vitro studies demonstrated that the chloride containing bioactive glasses are highly degradable and form apatite-like phase within three hours in Tris buffer and, therefore, are certainly suitable for use in remineralising toothpastes. The dissolution rate of the glass was found to increase with CaCl2 content. Faster dissolving bioactive glasses may be attractive for more resorbable bone grafts and scaffolds.

Molecular level-based bioactive glass-poly (caprolactone) hybrids monoliths with porous structure for bone tissue repair

Molecular level-based silicate bioactive glass (BG)-polymer hybrid materials have attracted much attention in bone tissue regeneration, due to their biomimetic structure and bioactivity. However, few successes have been achieved for preparing synthetic biopolymers-based bioactive glass hybrid materials, because of their non-miscible characteristic. Here, the molecular level scale bioactive glass-poly (ε-caprolactone) (MBG-PCL) hybrid monoliths with porous surface structure were successfully fabricated by a polydimethylsiloxane modified sol-gel technique. The as-prepared hybrid monolith presented a porous structure and crack-free morphology. The in vitro bioactivity test showed that the novel MBG-PCL hybrid structure exhibited high apatite-forming ability in simulated body fluid (SBF). The composition, porous structure, as well as high bioactivity of the hybrid monoliths make them a promising candidate as bioactive implants for bone tissue regeneration.

Tailoring of Bone Scaffold Properties Using Silicate/Phosphate Glass Mixtures

Different ratios of a resorbable phosphate glass (ICEL) and a bioactive silicate glass (CEL2) were co-sintered to obtain 3D porous scaffolds by gel-cast foaming method. The scaffold morphology, crystalline phases and compressive strength were studied. All the scaffolds showed a 3D structure with highly interconnected pores. The ICEL/CEL2 co-sintering resulted in a lower shrinkage leading to higher scaffold porosity (more than 70 vol%) compared to pure ICEL and CEL2 (about 65 vol%). Tuning ICEL/CEL2 ratio allowed the modulation of the scaffold resorption rate, with weight loss ranging from 20% to 75% after soaking for 3 months in simulated body fluid. Scaffolds containing higher amount of CEL2 silicate glass, resulted in a very high bioactivity.In vitrobiological test showed no toxic effect of the scaffolds on human osteoblast-like cells.

Development and effect of different bioactive silicate glass scaffolds: In vitro evaluation for use as a bone drug delivery system

Local drug delivery systems to bone have attracted appreciable attention due to their efficacy to improve drug delivery, healing and regeneration. In this paper, development and characterization of new formulations of bioactive glass into a porous scaffold has been reported for its suitability to act as a drug delivery system in the management of bone infections, in vitro. Two new glass compositions based on SiO2–Na2O–ZnO–CaO–MgO–P2O5 system (BGZ and MBG) have been developed which after thorough chemical and phase evaluation, studied for acellular static in vitro bioactivity in SBF. Porous scaffolds made of these glasses have been fabricated and characterized thoroughly for bioactivity study, SEM, XRD, in vitro cytotoxicity, MTT assay and wound healing assay using human osteocarcoma cells. Finally, gatifloxacin was loaded into the porous scaffold by vacuum infiltration method and in vitro drug release kinetics have been studied with varying parameters including dissolution medium (PBS and SBF) and with/without impregnation chitosan. Suitable model has also been proposed for the kinetics. 63–66% porous and 5–50μm almost unimodal porous MBG and BGZ bioactive glass scaffolds were capable of releasing drugs successfully for 43 days at concentrations to treat orthopedic infections. In addition, it was also observed that the release of drug followed Peppas–Korsmeyer release pattern based on Fickian diffusion, while 0.5–1% chitosan coating on the scaffolds decreased the burst release and overall release of drug. The results also indicated that MBG based scaffolds were bioactive, biocompatible, noncytotoxic and exhibited excellent wound healing potential while BGZ was mildly cytotoxic with moderate wound healing potential. These results strongly suggest that MBG scaffolds appear to be a suitable bone drug delivery system in orthopedic infections treatment and as bone void fillers, but BGZ should be handled with caution or studied elaborately in detail further to ascertain and confirm the cytotoxic nature and wound healing potential of this glass.

Towards the synthesis of an Mg-containing silicate glass–ceramic to be used as a scaffold for cementum/alveolar bone regeneration

The gradual destruction of periodontal tissue and in particular the reduction of alveolar bone height which can ultimately lead to tooth loss is a common problem in patients suffering from periodontal disease. The aim of the present work was to investigate the sol–gel synthesis and characterization of a family of new Mg-containing bioactive silicate glasses for applications in cementum/alveolar bone regeneration. Their microstructural, biological and mechanical characteristics were optimized for the fabrication of functional bioceramic scaffolds using the foam replica technique. The optimal glass composition for periodontal tissue replacement was found to contain 60mol% SiO2, 30mol% CaO and 10mol% MgO. After sintering, this composition had enhanced mechanical properties combined with the desired apatite-forming ability, which was tested in simulated body fluid (SBF) for up to 5 days. In vitro analysis revealed positive effects of these scaffolds on bone marrow stromal cells.

Evaluation of antibacterial and cytotoxic effects of nano-sized bioactive glass/collagen composites releasing tetracycline hydrochloride

To evaluate the antibacterial efficacy of silicate bioactive glass nanoparticles/collagen composites functionalized with tetracycline hydrochloride (TCH). Different concentrations of tetracycline hydrochloride (TCH) were incorporated on silicate bioactive glass nanoparticles/collagen composites by dipping these biomaterials for 48 h at 37°C in a solution of simulated body fluid (SBF) plus 0·05, 0·20 or 0·35 mg ml(-1) of the antibiotic. TCH release was assessed in double-distilled water at 37°C up to 72 h. The antibacterial activity of the samples has been evaluated in two ways: inhibition zone test and plate count method. The experiments were performed in vitro up to 48 h on four staphylococci strains (Staphylococcus aureus ATCC29213, ATCC25923, ATCC6538P and Staphylococcus epidermidis ATCC12228). The new composites were also tested for cytotoxicity on MG-63 human osteosarcoma cells. The results showed that the incorporation and release of TCH was dependent on the initial concentration of TCH in SBF. The biomaterials also inhibited the Staph. aureus cell growth even though the efficacy was similar for all concentration. On the other hand, no cytotoxic effects were found on osteoblast-like cells, even at the highest concentration. Considering all results, it can be concluded that the new composite acts as a suitable bioactive carrier of TCH and could have potential in the prevention of biomaterial related infections. The results suggest a potential application as wound dressing.

Cobalt-Releasing 1393 Bioactive Glass-Derived Scaffolds for Bone Tissue Engineering Applications

Loading biomaterials with angiogenic therapeutics has emerged as a promising approach for developing superior biomaterials for engineering bone constructs. In this context, cobalt-releasing materials are of interest as Co is a known angiogenic agent. In this study, we report on cobalt-releasing three-dimensional (3D) scaffolds based on a silicate bioactive glass. Novel melt-derived "1393" glass (53 wt % SiO2, 6 wt % Na2O, 12 wt % K2O, 5 wt % MgO, 20 wt % CaO, and 4 wt % P2O5) with CoO substituted for CaO was fabricated and was used to produce a 3D porous scaffold by the foam replica technique. Glass structural and thermal properties as well as scaffold macrostructure, compressive strength, acellular bioactivity, and Co release in simulated body fluid (SBF) were investigated. In particular, detailed insights into the physicochemical reactions occurring at the scaffold-fluid interface were derived from advanced micro-particle-induced X-ray emission/Rutherford backscattering spectrometry analysis. CoO is shown to act in a concentration-dependent manner as both a network former and a network modifier. At a concentration of 5 wt % CoO, the glass transition point (Tg) of the glass was reduced because of the replacement of stronger Si-O bonds with Co-O bonds in the glass network. Compressive strengths of >2 MPa were measured for Co-containing 1393-derived scaffolds, which are comparable to values of human spongy bone. SBF studies showed that all glass scaffolds form a calcium phosphate (CaP) layer, and for 1393-1Co and 1393-5Co, CaP layers with incorporated traces of Co were observed. The highest Co concentrations of ∼12 ppm were released in SBF after reaction for 21 days, which are known to be within therapeutic ranges reported for Co(2+) ions.

Bioceramic 3D Implants Produced by Laser Assisted Additive Manufacturing

Cranial defect restoration requires a suitable implant capable to fulfill protective and aesthetic functions, such as polymeric and metallic implants. Nevertheless, the former materials cannot provide osteointegration of the implant within the host bone nor implant resorption, which is also required in pediatricorthopedics for normal patient growth. Resorbable and osteoconductivebioceramics are employed, such as silicate bioactive glasses. Nevertheless, manufacturing based on conventional casting in graphite moulds is not effective for warped shape implants suitable for patient tailored treatments. In this work, we analyze the application of rapid prototyping based on laser cladding to manufacture bioactive glass implants for low load bearing bone restoration. This laser-assisted additive technique is capable to produce three-dimensional geometries tailored to patient, with reduced fabrication time and implant composition modification. The obtained samples were characterized; the relationships between the processing conditions and the measured features were studied, in addition to the biological behavior analysis.

Nanoscale Bioactive Glasses in Medical Applications

This review focuses on recent advances in the development and use of nanoscale silicate bioactive glasses for medical applications. In the context of materials for bone substitution, dental applications, and bone tissue engineering, nanoscale bioactive glasses have been gaining attention due to their expected superior osteoconductivity when compared with conventional (micrometer‐sized) bioactive glass materials. A detailed overview of recent developments in the field of nanoscale bioactive glasses will be given, including a summary of common fabrication methods and diverse application areas which include tissue engineering scaffolds and coatings, drug delivery devices, and dentistry. The nanofeatures characteristic of this type of bioactive glasses and the possibilities to expand their use in biomedical applications (nanomedicine) are highlighted.

Size-dependent degradation and bioactivity of borate bioactive glass

Abstract Borate bioactive glass has been shown to convert faster and more completely to hydroxyapatite and enhances new bone formation in vivo when compared to silicate bioactive glass. In this work, bioactive borate glass scaffolds, with a grid-like microstructure having different filament diameters (130±10 µm to 300±20 µm), were prepared by a robotic deposition technique. In vitro degradation and hydroxyapatite formation on borate bioactive glass scaffolds were investigated in a simulated body fluid (SBF) at 37 °C under static conditions. Mineralization of borate and silicate bioactive glass powders was also tested under the same conditions. When immersed in SBF, degradation rate of the scaffolds and conversion to a hydroxyapatite-like material showed dependence on filament diameter. Similarly, conversion of bioactive glass particles to calcium phosphate phase strongly depends on the particle size and the sample/SBF ratio of the system. Large particles and scaffolds composed of thick struts formed less apatite and degraded less completely compared with smaller particles and thinner struts. Results showed that it is possible to tailor the degradation rate and bioactivity by changing the filament diameter of the borate bioactive glass scaffolds produced by robocasting.

Direct Probing of the Phosphate-Ion Distribution in Bioactive Silicate Glasses by Solid-State NMR: Evidence for Transitions between Random/Clustered Scenarios

By employing 31P multiple-quantum coherence-based solid-state nuclear magnetic resonance spectroscopy, we present the first comprehensive experimental assessment of the nature of the orthophosphate-ion distributions in silicate-based bioactive glasses (BGs). Results are provided both from melt-prepared BG and evaporation-induced self-assembly-derived mesoporous bioactive glass (MBG) structures of distinct compositions. The phosphate species are randomly dispersed in melt-derived BGs (comprising 44–55 mol % SiO2) of the Na2O–CaO–SiO2–P2O5 system, whereas a Si-rich (86 mol % SiO2) and Ca-poor ordered MBG structure exhibits nanometer-sized amorphous calcium phosphate clusters, conservatively estimated to comprise at least nine orthophosphate groups. A Ca-richer MBG (58 mol % SiO2) reveals a less pronounced phosphate clustering. We rationalize the variable structural role of P in these amorphous biomaterials.

Conversion of melt-derived microfibrous borate (13-93B3) and silicate (45S5) bioactive glass in a simulated body fluid

Microfibrous bioactive glasses are showing a considerable capacity to heal soft tissue wounds, but little information is available on the mechanism of healing. In the present study, the conversion of microfibrous borate bioactive glass (diameter=0.2-5μm) with the composition designated 13-93B3 (5.5 Na2O, 11.1 K2O, 4.6 MgO, 18.5 CaO, 3.7 P2O5, 56.6 B2O3 wt%) was evaluated in vitro as a function of immersion time in a simulated body fluid (SBF) at 37°C using structural and chemical techniques. Silicate 45S5glass microfibers (45 SiO2, 24.5 Na2O, 24.5 CaO, 6 P2O5 wt%) were also studied for comparison. Microfibrous 13-93B3 glass degraded almost completely and converted to a calcium phosphate material within 7-14days in SBF, whereas>85% of the silica remained in the 45S5 microfibers, forming a silica gel phase. An amorphous calcium phosphate (ACP) product that formed on the 13-93B3 microfibers crystallized at a slower rate to hydroxyapatite (HA) when compared to the ACP that formed on the 45S5 fibers. For immersion times>3days, the 13-93B3 fibers released a higher concentration of Ca into the SBF than the 45S5 fibers. The fast and more complete degradation, slow crystallization of the ACP product, and higher concentration of dissolved Ca in SBF could contribute to the capacity of the microfibrous borate 13-93B3 glass to heal soft tissue wounds.

Magnesium‐Containing Bioactive Glasses for Biomedical Applications

The importance ofMgin the human body, its key role in bone tissue development, in addition to its application to improve and modify physical, thermal, and mechanical properties of bioactive silicate glasses, makeMga very interesting element as a component of bioactive glasses for medical applications. AlthoughMgis a typical element in the composition of numerous developed bioactive glasses, the analysis of the literature reveals that further research is required to gain comprehensive understanding about the effects ofMgOon bioactive glass structure and properties. This article presents a comprehensive overview of the field ofMg‐containing bioactive glasses discussing available compositions and summarizing existing knowledge on effects ofMgOon glass properties. The biomedical applications of several developed glasses are discussed highlighting the distinct effects ofMgin relevant areas, such as bioactivity and cell response, and focusing on the most common applications for these glasses, such as bone cements, bioactive coatings, and scaffolds for bone tissue engineering. The effect ofMgon bone development is discussed and avenues for future research in the field are proposed, emphasizing the need to investigate unstudied properties of (already developed)Mg‐containing glass compositions, such as angiogenesis‐stimulating action and the effect on osteoclast functions, to develop newMg‐containing bioactive glasses as well as to make products of different shape designs such as nanoparticles, fibers, and complex porous structures.