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The study aimed at preparing Ag-doped bioactive glass (BG) nanoparticles containing 5 wt% Ag2O using a new modified Stober method (Ag-BGm) and the conventional sol-gel method (Ag-BGsg). The aim of employing the new Ag-doping mechanism is to implement a relatively short process to incorporate higher concentration of silver (Ag+) ions in an attempt to combine the antibacterial activity of silver with the bioactivity of BG. SEM and TEM micrographs showed that Ag-BGm nanoparticles were mondispersed, and spherical, while Ag-BGsg nanoparticles were formed of highly porous irregular agglomerated particles. A significantly higher silicon, calcium and silver ions release from the Ag-BGsg was evident, as compared to Ag-BGm, in deionized water (DIW). In vitro bioactivity test showed rapid bioactive properties of Ag-BGsg in simulated body fluid (SBF), as compared to Ag-BGm. Both BGs showed antibacterial effect against E. coli O157: H7 wild type strain 93111 and S. aureus ATCC 25923 as evident by the disc diffusion assay, but Ag-BGsg showed significantly higher mean inhibition zone compared to Ag-BGm. It may be concluded that both Ag-BGsg and Ag-BGm has the potential to be used as bone substitute materials with the Ag-BGsg being more promising due to its high bioactivity and antibacterial effect.

Boron is considered to influence the performance of several metabolic enzymes and boron deficiency is associated with impaired growth and abnormal bone development. As such, boron is a beneficial bioactive element for animals and humans. It is also well known that boron stimulates wound healing and improves bone health. The addition of boron in different proportions to bioactive glasses has significant effects on glass structure, glass processing parameters, biodegradability, biocompatibility, bioactivity and cytotoxicity. Different compositions of bioactive glasses (BGs) containing boron, including boron-doped, borosilicate and borate glasses, are being investigated for bone and soft tissue engineering under the premise that these BGs are suitable carriers of boron, indicating controlled release of B species in the biological environment. This paper reviews up to date research and applications of borate, borosilicate, and boron doped silicate and phosphate BGs focussing on their physical, structural, degradation and biological properties for hard and soft tissue regeneration.

Three dimensional TiO2 scaffolds are receiving renewed attention for bone tissue engineering (TE) due to their biocompatibility and attractive mechanical properties. However the bioactivity of these scaffolds is comparatively lower than that of bioactive glass or hydroxyapatite (HA) scaffolds. One strategy to improve bioactivity is to functionalize the surface of the scaffolds using biomolecules. Alkaline phosphatase (ALP) was chosen in this study due to its important role in the bone mineralization process. The current study investigated the ALP functionalization of 3D titanium dioxide scaffolds using self-polymerization of dopamine. Robust titanium scaffolds (compressive strength∼2.7 ± 0.3 MPa) were produced via foam replica method. Enzyme grafting was performed by dip-coating in polydopamine/ALP solution. The presence of ALP was indirectly confirmed by contact angle measurements and enzymatic activity study. The influence of the enzyme on the bioactivity, e.g. hydroxyapatite formation on the scaffold surface, was measured in simulated body fluid (SBF). After 28 days in SBF, 5 mg ALP coated titania scaffolds exhibited increased hydroxyapatite formation. It was thus confirmed that ALP enhances the bioactivity of titania scaffolds, converting an inert bioceramic in an attractive bioactive system for bone TE., Graphical abstract Image 1, Highlights • TiO2 scaffolds of competent mechanical properties fabricated by foam replica method. • Bioactivity enhanced by functionalization with alkaline phosphatase (ALP). • ALP functionalization achieved by self-polymerization of dopamine.

Different bioactive glasses (BGs), bioceramics, and their composites were extensively analyzed in terms of biological responsiveness and angiogenic potential. In particular several inorganic materials were considered, namely the widely used 45S5 BG, an experimental BG with low tendency to crystallize, other three experimental BGs doped with strontium and/or magnesium, a commercial hydroxyapatite (HA), and two BG-HA composites (with varying percentages of BG and HA). All these materials were ad hoc prepared and in vitro tested by means of an extensive biological analysis, such as MC3T3-E1 cell viability and proliferation by direct contact assay, alkaline phosphatase activity, mineralized matrix deposition analysis by alizarin red staining, as well as evaluation of angiogenic potential and vascular endothelial growth factor release using ST2 cells. Thus, this investigation allows gaining a deeper insight into the biological performance of different inorganic material categories, and to critically compare the different possible solutions, as bone/tissue substitutes for enhanced healing and repair, in terms of bioactivity and regenerative potential.

Boron-containing bioactive glasses (BGs) are being extensively researched for the treatment and regeneration of bone defects because of their osteostimulatory and neovascularization potential. In this study, we report the effects of the ionic dissolution products (IDPs) of different boron-doped, borosilicate, and borate BG scaffolds on mouse bone marrow stromal cells in vitro, using an angiogenesis assay. Five different BG scaffolds of the system SiO2–Na2O–K2O–MgO–CaO–P2O5–B2O3 (with varying amounts of SiO2 and B2O3) were fabricated by the foam replication technique. Bone marrow stromal cells were cultivated in contact with the IDPs of the boron-containing BG scaffolds at different concentrations for 48 h. The expression and secretion of vascular endothelial growth factor (VEGF) from the cultured cells was measured quantitatively using the VEGF ELISA Kit. Cell viability and cell morphology were determined using WST-8 assay and H&E staining, respectively. The cellular response was found to be dependent on boron content and the B release profile from the glasses corresponded to the positive or negative biological activity of the BGs.

We report the development and characterization of boron-releasing highly porous three-dimensional bioactive glass (BG) scaffolds fabricated by the foam replica technique. Three types of bioactive glasses with (wt%) 0.2%, 12.5%, 25% B2O3, and related varying SiO2 contents (wt%): 50%, 37.5%, and 25%, were investigated. The well-known 13-93 (silicate) and 13-93B3 (borate) (in wt% – 56.6% B2O3, 5.5% Na2O, 11.1% K2O, 4.6% MgO, 18.5% CaO, 3.7% P2O5) BGs were used as controls to study the influence of the presence of boron on the mechanical properties, surface reactivity, and cytotoxicity of scaffolds. Surface morphology and surface properties of the BG scaffolds were measured. X-ray diffraction (XRD) analyses showed that the scaffolds of all five compositions were amorphous. The scaffolds with 12.5 wt% B2O3 exhibited satisfactory compressive strength in the range of 1–2 MPa. A dissolution study in cell culture medium was carried out, and ion release profiles, and apatite formation of the scaffolds were assessed. The cytotoxicity of the scaffolds was evaluated using a stromal cell line (ST2). Cells were found to attach and spread well on the scaffolds' surfaces. We conclude that borosilicate scaffolds containing 12.5 wt% B2O3 provide the best combination of properties, including relatively high mechanical strength, apatite formation, and cytocompatibility, and thus, they are promising candidates for bone tissue engineering.

Mesoporous bioactive glass nanoparticles (MBG) are multifunctional building blocks for tissue regeneration and nanomedicine applications. Incorporation of biologically active ions can endow MBG with additional functionalities toward promoted therapeutic effects. Here, boron is incorporated into MBG by using a sol–gel approach. The concentration of boron incorporated is controllable by tuning the amount of boron precursor. Two types of boron‐doped MBG, namely 10B‐ and 15B‐MBG (5.8 and 6.5 mol% of B2O3, respectively) are synthesized. Boron incorporation does not significantly influence the particle morphology. All synthesized particles exhibit a sphere‐like shape with a size ranging from 100 to 300 nm. 10B‐ and 15B‐MBG show large specific surface area (346 and 320 m² g−1, respectively) and pore volume. Both boron‐doped MBG exhibit remarkable in vitro bioactivity and noncytotoxicity. Boron incorporation is shown to reduce the inflammatory response linked to macrophages as indicated by downregulated expression of pro‐inflammatory genes. However, boron incorporation delays the osteogenic differentiation in osteoblasts as indicated by the downregulated expression of pro‐osteogenic genes. The results demonstrate the promising potential of using boron‐doped MBG to modulate inflammatory response for bone regeneration under inflammatory conditions, as shown in this study for the first time.

Certain biomaterials are capable of inducing the secretion of Vascular Endothelial Growth Factor (VEGF) from cells exposed to their biochemical influence, which plays a vital role in stimulating angiogenesis. Looking for this capacity, in this study three porous glasses were synthesized and characterized. The objective of this study was to determine the concentration of the glass particles that, being out of the cytotoxic range, could increase VEGF secretion. The viability of cultivated bone marrow stromal cells (ST-2) was assessed. The samples were examined with light microscopy (LM) after the histochemical staining for haematoxylin and eosin (HE). The biological activity of glasses was evaluated in terms of the influence of the Cu2+ and Sr2+ ions on the cells. The dissolution products of CuSr-1 and CuSr-2.5 produced the highest secretion of VEGF from ST-2 cells after 48 h of incubation. The combination of Cu2+ and Sr2+ lays the foundation for engineering a bioactive glass than can lead to vascularized, functional bone tissue when used in bone regeneration applications., Comment: 21 pages, 7 figures

We report for the first time on the combination of polymer replication method and flock technology to produce 45S5 bioactive glass (45S5 BG) scaffolds with a fibrous surface morphology suitable for tissue engineering (TE). In order to develop a fibrous morphology on the surface of the scaffolds, electroflocking was used with BG scaffolds serving as the substrate. Gelatin was used as the adhesive and short polyamide (PA) fibers were electroflocked on the top surface to produce scaffolds with anisotropic properties. In order to improve the stability of the adhesive (gelatin) and to create a better bonding between the fibers and the adhesive, a crosslinking step was carried out. The porosity on the surface could be tailored by varying the flocking time which, in turn, was shown to influence the packing density of the fibers. In vitro bioactivity study in simulated body fluid (SBF) was carried out and complete mineralization of the scaffold, including on the PA fibers, was detected and characterized using various techniques.

A simple yet promising approach to construct bi-layered scaffolds using bioactive ceramics and biodegradable polymers is presented. This method involves two versatile fabrication techniques used in the field of TE: foam replication process and electrospinning. By the foam replication method, three-dimensional 45S5 bioactive glass (BG)-based scaffolds with high porosity, in the range of 95.8 ± 0.9 %, were produced. To improve the mechanical properties of the BG scaffolds, dip-coating using polycaprolactone (PCL) was performed, which led to a significant increase in the compressive strength of the scaffolds. In order to develop a bi-layered construct, bead-less submicrometric fibers of collagen-PCL were electrospun over the PCL-coated BG scaffolds. Surface morphology, surface properties and mechanical strength of the bi-layered construct were evaluated using scanning electron microscopy analysis, contact angle measurements and compressive strength testing, respectively. In vitro degradation of the collagen-PCL fibers in phosphate buffered saline and in vitro bioactivity of the bi-layered constructs in simulated body fluid were investigated. Formation of hydroxyapatite on the PCL-coated BG and along the morphology of the collagen-PCL fibers was ascertained using different characterization techniques. The bi-layered construct is intended for interface tissue engineering applications where the PCL-coated BG scaffold, which is highly bioactive, can serve as a support for the bone side and the composite collagen-PCL submicrometric fibers are intended for the cartilage side.

This study evaluated the influence of ionic dissolution products of a novel Ca-enriched silicate bioactive glass compared to commercial available hydroxyapaptite samples (Endobonr) on cell activity and vascular endothelial growth factor (VEGF) release in vitro. Bone marrow stromal cells (ST-2) were cultivated with the supernatant of granules of different sizes and at different concentrations (0-1 wt/vol % of granules) for 48 h. In addition to in vitro studies, Ca-ion release from all as cell morphology observation revealed no cytotoxic effect of the released products from all tested materials. It was found that supernatants from granules in concentrations of 1 wt/vol %enhanced the VEGF release from ST2 cells, which is important as a marker of the vascularisation ability of the glass during the bone healing process.

Three-dimensional 45S5 bioactive glass (BG)-based scaffolds are being investigated for bone regeneration. Besides structural properties, controlled time-dependent alteration of scaffold morphology is crucial to achieve optimal scaffold characteristics for successful bone repair. There is no in vitro evidence concerning the dependence between structural characteristics and dissolution behavior of 45S5 BG-based scaffolds of different morphology. In this study, the dissolution behavior of scaffolds fabricated by the foam replica method using polyurethane foam (Group A) and maritime sponge Spongia Agaricina (Group B) as sacrificial templates was analyzed by micro-computed-tomography (µCT). The scaffolds were immersed in Dulbecco’s Modified Eagle Medium for 56 days under static cell culture conditions and underwent µCT-analysis initially, and after 7, 14, and 56 days. Group A showed high porosity (91%) and trabecular structure formed by macro-pores (average diameter 692 µm ± 72 µm). Group-B-scaffolds were less porous (51%), revealing an optimal pore size distribution within the window of 110–500 µm pore size diameter, combined with superior mechanical stability. Both groups showed similar structural alteration upon immersion. Surface area and scaffold volume increased whilst density decreased, reflecting initial dissolution followed by hydroxycarbonate-apatite-layer-formation on the scaffold surfaces. In vitro- and/or in vivo-testing of cell-seeded BG-scaffolds used in this study should be performed to evaluate the BG-scaffolds’ time-dependent osteogenic properties in relation to the measured in vitro structural changes.

Bioactive glasses (BG) are versatile materials for various biomedical applications, including bone regeneration and wound healing, due to their bone bonding, antibacterial, osteogenic, and angiogenic properties. In this study, we aimed to enhance the antibacterial activity of SiO2-CaO mesoporous bioactive glass nanoparticles (MBGN) by incorporating silver (Ag) through a surface modification approach. The modified Ag-containing nanoparticles (Ag-MBGN) maintained spherical shape, mesoporous structure, high dispersity, and apatite-forming ability after the surface functionalization. The antibacterial activity of Ag-MBGN was assessed firstly using a planktonic bacteria model. Moreover, a 3D tissue-engineered infected skin model was used for the first time to evaluate the antibacterial activity of Ag-MBGN at the usage dose of 1 mg/mL. In the planktonic bacteria model, Ag-MBGN exhibited a significant antibacterial effect against both Pseudomonas aeruginosa and Staphylococcus aureus in comparison to non-engineered (Ag-free) MBGN and the blank control. Moreover, Ag-MBGN did not show cytotoxicity towards fibroblasts at the usage dose. However, in the 3D infected skin model, Ag-MBGN only demonstrated antibacterial activity against S. aureus whereas their antibacterial action against P. aeruginosa was inhibited. In conclusion, surface modification by Ag incorporation is a feasible approach to enhance the antibacterial activity of MBGN without significantly impacting their morphology, polydispersity, and apatite-forming ability. The prepared Ag-MBGN are attractive building blocks for the development of 3D antibacterial scaffolds for tissue engineering.

Regeneration of bone and cartilage tissues has been an important issue for biological repair in the field of regenerative medicine. The rapidly emerging field of tissue engineering holds great promise for repair and generation of functional bone and cartilage substitutes with a combination of biomaterials, cells, drugs and growth factors. Scaffolds play a pivotal role in tissue engineering as they mimic the natural extracellular matrix (ECM) and play an important role in guiding cell adhesion and proliferation, and maintaining the normal phenotype of the tissues. The use of tissue-engineered grafts based on scaffolds has found to be a more effective method than conventional implantations of autograft, allograft, xenograft. In recent years much attention has been given to electrospinning as a feasible and versatile technique for fabrication of nanofibrous scaffolds, with large surface area to volume ratio, high porosity, mechanical properties and physical dimension similar to the ECM of natural tissues. Extensive research has been carried out for fabrication polymeric nanofibrous substrates with incorporation of hydroxyapatite nanoparticles or bone morphogenetic protein molecules for efficient tissue repair. Here we review on the literature of electrospun nanofibrous scaffolds, their modifications, and advances aimed towards the rapid regeneration of bone and cartilage.

The use of bioceramic scaffolds for hard tissue repair, augmentation, and substitution is continuously increasing in many dental and medical applications. It is well established that the in vivo biodegradation and bioresorption of ceramic scaffolds at rates appropriate to tissue regeneration play a vital role in enabling new tissue formation. Furthermore, the various ionic by-products of biodegradation of scaffolding materials result in the enrichment of the microenvironment, which can affect, positively or negatively, the proliferation and activity of cells. Therefore, the factors affecting degradation or the extent of dissolution of the scaffolding materials are important. The aim of this chapter is to discuss the processes of biodegradation or bioresorption of bioceramic scaffolds in terms of the physical, chemical, and biocompatibility that occur when in contact with simulated body fluids, cells, or living tissue, focusing on the applied characterization techniques.

Aim This study aims to compare visual outcomes and complications of iris-fixated (claw) intraocular lens (IFIOL) implantation with those of posterior chamber intraocular lens (PCIOL) implantation in children with traumatic cataract. Settings and design Retrospective observational clinical audit. Materials and methods A total of 50 pediatric traumatic cataract cases that underwent lens removal and IOL implantation (IFIOL or PCIOL) with or without corneal or corneoscleral tear repair between January 2009 and December 2013 were analyzed. After meeting the eligibility criteria, their pre- and postoperative visual outcomes and complication rates were recorded. Data were analyzed descriptively. Results Out of 50 children, IFIOL and PCIOL implantations were performed in one eye of each of 25 children. Their mean age was 11 ± 4 years (range 4–18 years). Primary (cataract removal with lens implantation) and secondary (corneal tear repair followed by cataract removal with lens implantation) procedures were performed in 19 (76%) and six (24%) children in the IFIOL group and in 21 (84%) and four (16%) children in the PCIOL group, respectively. There was an improvement in best corrected visual acuity postimplantation in both the IFIOL and the PCIOL group, and no significant difference in the logarithm of the minimum angle of resolution of best corrected visual acuity was observed between the two groups over 36 months. Only three eyes in the IFIOL group developed complications: one eye developed secondary glaucoma, one disenclavation of IOL haptic, and one cystoid macular edema. Conclusion Both IFIOL and PCIOL implantations have good visual outcomes and minimal postoperative complications; therefore, IFIOL can be used as an alternative to PCIOL in children with traumatic cataract with inadequate capsular support.

Zinc is a vital and beneficial trace element found in the human body. Though found in small proportions, zinc performs a variety of functions in relation to the immune system, cell division, fertility and the body growth and maintenance. In particular, zinc is proven to be a necessary element for the formation, mineralization, development and maintenance of healthy bones. Considering this attractive attributes of zinc, recent research has widely focused on using zinc along with silicate-based bioactive glasses for bone tissue engineering applications. This paper reviews relevant literature discussing the significance of zinc in the human body, along with its ability to enhance antibacterial effects, bioactivity and distinct physical, structural and mechanical properties of bioactive glasses. In this context, even if the present analysis is not meant to be exhaustive and only representative studies are discussed, literature results confirm that it is essential to understand the properties of zinc-containing bioactive glasses with respect to their in vitro biological behavior, possible cytotoxic effects and degradation characteristics to be able to effectively apply these glasses in bone regeneration strategies. Topics attracting increasing research efforts in this field are elaborated in detail in this review, including a summary of the structural, physical, biological and mechanical properties of zinc-containing bioactive glasses. This paper also presents an overview of the various applications in which zinc-containing bioactive glasses are considered for use as bone tissue scaffolds, bone filling granules, bioactive coatings and bone cements, and advances and remaining challenges are highlighted.

Myocardial infarction is the major cause of death in many industrialized nations as it leads to end-stage heart failure. Tissue engineering (TE) approaches for treatment of the infarcted tissue have gained huge attention over the recent years and research in this direction mainly aims for the optimization of a biomaterial scaffold with suitable cell source for tissue regeneration. In this regard, we fabricated completely natural polymeric scaffolds using fibrinogen and gelatin in two different weight ratios and performed cross-linking [Fib/Gel(1:4)-CL; Fib/Gel(2:3)-CL] while cross-linked fibrinogen scaffolds were used as the control. The fiber diameters of the fabricated scaffolds were obtained in the range of 150-300 nm. Chemical characterization of the scaffolds confirmed the presence of both the proteins and showed the absence of any chemical reactions between them. The tensile strength and the stiffness values of Fib/Gel(1:4)-CL matrices were found to be 0.0125 and 0.46 MPa, respectively, which were much similar to the innate properties of the native myocardium. Cell culture studies using human cardiomyocytes revealed higher cell proliferation on Fib/Gel(1:4)-CL scaffolds compared to cell proliferation on Fib/Gel(2:3)-CL scaffolds, which was even higher than the cell proliferation on cross-linked fibrinogen scaffolds. Moreover, the cardiomyocytes seeded on composite substrates expressed the typical functional cardiac proteins such as alpha-actinin, troponin I, connexin-43, and myosin heavy chain, and could be potential for application in cardiac TE.

Purpose: To evaluate the postoperative visual outcomes and complications of posterior iris fixated intraocular lens (IFIOL) implantation for pediatric traumatic cataract. Materials and Methods: A retrospective clinical audit was performed of all the pediatric traumatic cataract patients who underwent lens removal and iris fixated lens implantation due to inadequate capsular support with or without corneal tear repair between January 2009 and December 2013. Data were collected and analyzed on the preoperative and postoperative visual outcomes and complications. Results: Twenty-five children (25 eyes; 21 males and 4 females) were enrolled with the mean age of 11 ± 4.0 years. There were 72% of eyes that underwent primary cataract removal with IFIOL implantation. Twenty-eight percent of eyes underwent corneal tear repair prior to intraocular lens (IOL) implantation. Preoperative best corrected visual acuity (BCVA) was hand motion in 32% eyes, counting fingers in 24%, and perception of light in 44%. Postoperative BCVA of 0-0.2 logarithm of minimum angle of resolution was reported in the 64% of eyes. One eye developed secondary glaucoma, one eye underwent re-enclavation, and none developed retinal complications. Conclusion: Posterior IFIOL implantation resulted in an improved visual outcome, low incidence of postoperative complications, and is a good alternative to other IOL, in the cases of pediatric traumatic cataract without adequate capsular support.

The extracellular matrix is a complex biological structure encoded with various proteins, among which the collagen family is the most significant and abundant of all, contributing 30–35% of the whole-body protein. “Collagen” is a generic term for proteins that forms a triple-helical structure with three polypeptide chains, and around 29 types of collagen have been identified up to now. Although most of the members of the collagen family form such supramolecular structures, extensive diversity exists between each type of collagen. The diversity is not only based on the molecular assembly and supramolecular structures of collagen types but is also observed within its tissue distribution, function, and pathology. Collagens possess complex hierarchical structures and are present in various forms such as collagen fibrils (1.5–3.5 nm wide), collagen fibers (50–70 nm wide), and collagen bundles (150–250 nm wide), with distinct properties characteristic of each tissue providing elasticity to skin, softness of the cartilage, stiffness of the bone and tendon, transparency of the cornea, opaqueness of the sclera, etc. There exists an exclusive relation between the structural features of collagen in human tissues (such as the collagen composition, collagen fibril length and diameter, collagen distribution, and collagen fiber orientation) and its tissue-specific mechanical properties. In bone, a transverse collagen fiber orientation prevails in regions of higher compressive stress whereas longitudinally oriented collagen fibers correlate to higher tensile stress. The immense versatility of collagen compels a thorough understanding of the collagen types and this review discusses the major types of collagen found in different human tissues, highlighting their tissue-specific uniqueness based on their structure and mechanical function. The changes in collagen during a specific tissue damage or injury are discussed further, focusing on the many tissue engineering applications for which collagen scaffolds are currently being applied.