Glass Scaffolds Research Articles

Three-dimensional polymer coated 45S5-type bioactive glass scaffolds seeded with human mesenchymal stem cells show bone formation in vivo.

45S5-type bioactive glasses are a promising alternative to established substitutes for the treatment of bone defects. Because the three-dimensional (3D) structure of bone substitutes is crucial for bone ingrowth and formation, we evaluated the osteoinductive properties of different polymer coated 3D-45S5 bioactive glass (BG) scaffolds seeded with human mesenchymal stem cells (hMSC) in vivo. BG scaffolds coated with gelatin, cross-linked gelatin, and poly(3-hydroxybutyrate-co-3-hydroxyvalerate) were seeded with hMSC prior to implantation into severe combined immunodeficiency mice. Newly formed bone was evaluated with histomorphometry and micro-computed tomography. Bone formation was detectable in all groups, whereas the gelatin-coated BG scaffolds showed the best results and should be considered in further studies.

Creation of bioactive glass (13–93) scaffolds for structural bone repair using a combined finite element modeling and rapid prototyping approach

There is a clinical need for synthetic bioactive materials that can reliably repair intercalary skeletal tissue loss in load-bearing bones. Bioactive glasses have been investigated as one such material but their mechanical response has been a concern. Previously, we created bioactive silicate glass (13–93) scaffolds with a uniform grid-like microstructure which showed a compressive strength comparable to human cortical bone but a much lower flexural strength. In the present study, finite element modeling (FEM) was used to re-design the scaffold microstructure to improve its flexural strength without significantly lowering its compressive strength and ability to support bone infiltration in vivo. Then scaffolds with the requisite microstructures were created by a robotic deposition method and tested in four-point bending and compression to validate the FEM simulations. In general, the data validated the predictions of the FEM simulations. Scaffolds with a porosity gradient, composed of a less porous outer region and a more porous inner region, showed a flexural strength (34±5MPa) that was more than twice the value for the uniform grid-like microstructure (15±5MPa) and a higher compressive strength (88±20MPa) than the grid-like microstructure (72±10MPa). Upon implantation of the scaffolds for 12weeks in rat calvarial defects in vivo, the amount of new bone that infiltrated the pore space of the scaffolds with the porosity gradient (37±16%) was similar to that for the grid-like scaffolds (35±6%). These scaffolds with a porosity gradient that better mimics the microstructure of human long bone could provide more reliable implants for structural bone repair.

Fabrication and characterization of strontium incorporated 3-D bioactive glass scaffolds for bone tissue from biosilica

Bioactive glass scaffolds that contain silica are high viable biomaterials as bone supporters for bone tissue engineering due to their bioactive behaviour in simulated body fluid (SBF). In the human body, these materials help inorganic bone structure formation due to a combination of the particular ratio of elements such as silicon (Si), calcium (Ca), sodium (Na) and phosphorus (P), and the doping of strontium (Sr) into the scaffold structure increases their bioactive behaviour. In this study, bioactive glass scaffolds were produced by using rice hull ash (RHA) silica and commercial silica based bioactive glasses. The structural properties of scaffolds such as pore size, porosity and also the bioactive behaviour were investigated. The results showed that undoped and Sr-doped RHA silica-based bioactive glass scaffolds have better bioactivity than that of commercial silica based bioactive glass scaffolds. Moreover, undoped and Sr-doped RHA silica-based bioactive glass scaffolds will be able to be used instead of undoped and Sr-doped commercial silica based bioactive glass scaffolds for bone regeneration applications. Scaffolds that are produced from undoped or Sr-doped RHA silica have high potential to form new bone for bone defects in tissue engineering.

Physico-chemical and biological studies on three-dimensional porous silk/spray-dried mesoporous bioactive glass scaffolds

The incorporation of a bioactive inorganic phase in polymeric scaffolds is a good strategy for the improvement of the bioactivity and the mechanical properties, which represent crucial features in the field of bone tissue engineering. In this study, spray-dried mesoporous bioactive glass particles (SD-MBG), belonging to the binary system of SiO2-CaO (80:20mol%), were used to prepare composite scaffolds by freeze-drying technique, using a silk fibroin matrix. The physico-chemical and biological properties of the scaffolds were extensively studied. The scaffolds showed a highly interconnected porosity with a mean pore size in the range of 150µm for both pure silk and silk/SD-MBG scaffolds. The elastic moduli of the silk and silk/SD-MBG scaffolds were 1.1±0.2MPa and 6.9±1.0MPa and compressive strength were 0.5±0.05MPa and 0.9±0.2MPa, respectively, showing a noticeable increase of the mechanical properties of the composite scaffolds compared to the silk ones. The contact angle value decreased from 105.3° to 71.2° with the incorporation of SD-MBG particles. Moreover, the SD-MBG incorporation countered the lack of bioactivity of the silk scaffolds inducing the precipitation of hydroxyapatite layer on their surface already after 1 day of incubation in simulated body fluid. The composite scaffolds showed good biocompatibility and a good alkaline phosphatase activity toward human mesenchymal stromal cells, showing the ability for their use as three-dimensional constructs for bone tissue engineering.

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.

Ion Release, Hydroxyapatite Conversion, and Cytotoxicity of Boron‐Containing Bioactive Glass Scaffolds

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.

Europium-Containing Mesoporous Bioactive Glass Scaffolds for Stimulating in Vitro and in Vivo Osteogenesis.

Bone tissue engineering offers a possible strategy for regenerating large bone defects, in which how to design beneficial scaffolds for accelerating bone formation remains significantly challenging. Europium, as an important rare earth element, has been used as a solid-state lighting material. However, there are few reports on whether Eu can be used for labeling bone tissue engineering scaffolds, and its biological effect on bone cells and bone tissue regeneration is unknown. In this study, we incorporated Eu into mesoporous bioactive glass (Eu-MBG) scaffolds by an in situ cotemplate method to achieve a bifunctional biomaterial with biolabeling and bone regeneration. The prepared Eu-MBG scaffolds have highly interconnective large pores (300-500 μm), a high specific surface area (140-290 m(2)/g), and well-ordered mesopores (5 nm) as well as uniformly distributed Eu. The incorporation of 2-5 mol % Eu into MBG scaffolds gives them a luminescent property. The in vitro degradation of Eu-MBG scaffolds has a functional effect on the change of the luminescence intensity. In addition, Eu-MBG can be used for labeling bone marrow stromal cells (BMSCs) in vitro and still presents a distinct luminescence signal in deep bone tissues in vivo to label new bone tissue via release of Eu ions. Furthermore, the incorporation of different contents of Eu (1, 2, and 5 mol %) into MBG scaffolds significantly enhances the osteogenic gene expression of BMSCs in the scaffolds. The Eu- and Si-containing ionic products released from Eu-MBG scaffolds distinctly promote the osteogenic differentiation of BMSCs. Critically sized femur defects in ovariectomized (OVX) rats are created to simulate an osteoporotic phenotype. The results show that Eu-MBG scaffolds significantly stimulate new bone formation in osteoporotic bone defects when compared to MBG scaffolds alone and Eu may be involved in the acceleration of bone regeneration in OVX rats. Our study for the first time reports that the incorporation of the rare earth element Eu into bioscaffolds has the ability to accelerate bone regeneration in vivo, and thus, the prepared Eu-MBG scaffolds possess bifunctional properties with biolabeling and bone regeneration.

In vivo evaluation of cerium, gallium and vanadium-doped borate-based bioactive glass scaffolds using rat subcutaneous implantation model

The main objective of this study was to evaluate the cerium, gallium and vanadium-containing bioactive borate glass scaffolds for soft tissue applications and determine the potential toxicity of these scaffolds on the adjacent tissues. The effects of the cerium, gallium and vanadium substitution on the soft tissue ingrowth and angiogenesis in porous borate based bioactive glass scaffolds were investigated using rat subcutaneous implantation model. For this purpose, bioactive borate glass powders containing therapeutic ions were prepared by melt-cast method and subsequently scaffolds were fabricated using polymer foam replication technique. The scaffolds were implanted subcutaneously for 4 weeks in Sprague Dawley rats. Bare borate glass scaffolds with the same microstructure were used as the control. Histology was used to evaluate tissue ingrowth and blood vessel formation in the implants. Additionally, the antibacterial activities of cerium, gallium and vanadium containing porous bioactive glass scaffolds were investigated in vitro by a zone inhibition method. Results revealed that addition of cerium ions to the borate glass network caused an increase in blood vessel formation. On the other hand, a decrease was obtained in angiogenesis in gallium and vanadium-containing glasses. All of the scaffolds prepared in the study did not show any antibacterial activity towards Escherichia coli and Staphylococcusaureus.

Constructing a highly bioactive 3D nanofibrous bioglass scaffold via bacterial cellulose-templated sol-gel approach

A novel three-dimensional (3D) nanofibrous bioactive glass (BG) scaffold was prepared via a template assisted sol-gel route using a 3D bacterial cellulose aerogel as the template followed by calcination. SEM and TEM results revealed that the as-prepared BG nanofibers had a diameter as small as 16 nm and the BG scaffold had a 3D interconnected porous structure. The in vitro bioactivity test confirmed that the BG nanofibrous scaffold was highly bioactive. The strategy presented in this work may open a new avenue for the development of tissue engineering scaffolds with fine inorganic nanofibers.

Bioactivity and Mechanical Stability of 45S5 Bioactive Glass Scaffolds Based on Natural Marine Sponges.

Bioactive glass (BG) based scaffolds (45S5 BG composition) were developed by the replica technique using natural marine sponges as sacrificial templates. The resulting scaffolds were characterized by superior mechanical properties (compression strength up to 4MPa) compared to conventional BG scaffolds prepared using polyurethane (PU) packaging foam as a template. This result was ascribed to a reduction of the total scaffold porosity without affecting the pore interconnectivity (>99%). It was demonstrated that the reduction of total porosity did not affect the bioactivity of the BG-based scaffolds, tested by immersion of scaffolds in simulated body fluid (SBF). After 1day of immersion in SBF, a homogeneous CaP deposit on the surface of the scaffolds was formed, which evolved over time into carbonate hydroxyapatite(HCA). Moreover, the enhanced mechanical properties of these scaffolds were constant over time in SBF; after an initial reduction of the maximum compressive strength upon 7days of immersion in SBF (to 1.2±0.2MPa), the strength values remained almost constant and higher than those of BG-based scaffolds prepared using PU foam (<0.05MPa). Preliminary cell culture tests with Saos-2 osteoblast cell line, namely direct and indirect tests, demonstrated that no toxic residues remained from the natural marine sponge templates and that cells were able to proliferate on the scaffold surfaces.

Indirect rapid prototyping of sol-gel hybrid glass scaffolds for bone regeneration – Effects of organic crosslinker valence, content and molecular weight on mechanical properties

We present a series of organic/inorganic hybrid sol-gel derived glasses, made from a tetraethoxysilane-derived silica sol (100% SiO2) and oligovalent organic crosslinkers functionalized with 3-isocyanatopropyltriethoxysilane. The material was susceptible to heat sterilization. The hybrids were processed into pore-interconnected scaffolds by an indirect rapid prototyping method, described here for the first time for sol-gel glass materials. A large panel of polyethylene oxide-derived 2- to 4-armed crosslinkers of molecular weights ranging between 170 and 8000Da were incorporated and their effect on scaffold mechanical properties was investigated. By multiple linear regression, ‘organic content’ and the ‘content of ethylene oxide units in the hybrid’ were identified as the main factors that determined compressive strength and modulus, respectively. In general, 3- and 4-armed crosslinkers performed better than linear molecules. Compression tests and cell culture experiments with osteoblast-like SaOS-2 cells showed that macroporous scaffolds can be produced with compressive strengths of up to 33±2MPa and with a pore structure that allows cells to grow deep into the scaffolds and form mineral deposits. Compressive moduli between 27±7MPa and 568±98MPa were obtained depending on the hybrid composition and problems associated with the inherent brittleness of sol-gel glass materials could be overcome. SaOS-2 cells showed cytocompatibility on hybrid glass scaffolds and mineral accumulation started as early as day 7. On day 14, we also found mineral accumulation on control hybrid glass scaffolds without cells, indicating a positive effect of the hybrid glass on mineral accumulation. Statement of SignificanceWe produced a hybrid sol-gel glass material with significantly improved mechanical properties towards an application in bone regeneration and processed the material into macroporous scaffolds of controlled architecture by indirect rapid prototyping. We were able to produce macroporous materials of relevant porosity and pore size with compressive moduli, covering the range reported for cancellous bone while an even higher compressive strength was maintained. By multiple linear regression, we identified crosslinker parameters, namely organic content and the content of ethylene oxide units in the hybrids that predominantly determined the mechanics of the hybrid materials. The scaffolds proved to be cytocompatible and induced mineralization in SaOS-2 cells. This provides new insight on the critical parameters for the design of the organic components of covalent hybrid sol-gel glasses.

A 45S5 Bioactive Glass Scaffold Reinforced with ZnO and MgO

A 45S5 Bioactive Glass Scaffold Reinforced with ZnO and MgO

Design and Fabrication of 3D printed Scaffolds with a Mechanical Strength Comparable to Cortical Bone to Repair Large Bone Defects.

A challenge in regenerating large bone defects under load is to create scaffolds with large and interconnected pores while providing a compressive strength comparable to cortical bone (100–150 MPa). Here we design a novel hexagonal architecture for a glass-ceramic scaffold to fabricate an anisotropic, highly porous three dimensional scaffolds with a compressive strength of 110 MPa. Scaffolds with hexagonal design demonstrated a high fatigue resistance (1,000,000 cycles at 1–10 MPa compressive cyclic load), failure reliability and flexural strength (30 MPa) compared with those for conventional architecture. The obtained strength is 150 times greater than values reported for polymeric and composite scaffolds and 5 times greater than reported values for ceramic and glass scaffolds at similar porosity. These scaffolds open avenues for treatment of load bearing bone defects in orthopaedic, dental and maxillofacial applications.

Bone healing in rabbit calvarial critical-sized defects filled with stem cells and growth factors combined with granular or solid scaffolds.

In pediatric neurosurgery, decompressive craniectomy and correction of congenital cranial anomalies can result in major cranial defects. Corrective cranioplasty for the repair of these critical-sized defects is not only a cosmetic issue. The limited availability of suitable autogenous bone and the morbidity of donor site harvesting have driven the search for new approaches with biodegradable and bioactive materials. This study aimed to assess the healing of rabbit calvarial critical-sized defects filled with osteogenic material, either with bioactive glass scaffolds or tricalcium phosphate granules in various combinations with adipose stem cells or bone marrow stem cells, BMP-2, BMP-7, or VEGF to enhance osteogenesis. Eighty-two bicortical full thickness critical-sized calvarial defects were operated. Five defects were left empty as negative control defects. The remaining 77 defects were filled with solid bioactive glass scaffolds or tricalcium phosphate granules seeded with adipose or bone marrow derived stem cells in combination with BMP-2, BMP-7, or VEGF. The defects were allowed to heal for 6 weeks before histologic and micro-CT analyses. Micro-CT examination at the 6-week post-operative time point revealed that defects filled with stem cell-seeded tricalcium phosphate granules resulted in new bone formation of 6.0 %, whereas defects with bioactive glass scaffolds with stem cells showed new bone formation of 0.5 to 1.7 %, depending on the growth factor used. This study suggests that tricalcium phosphate granules combined with stem cells have osteogenic potential superior to solid bioactive glass scaffolds with stem cells and growth factors.

Functionalized mesoporous bioactive glass scaffolds for enhanced bone tissue regeneration.

Mesoporous bioactive glass (MBG), which possesses excellent bioactivity, biocompatibility and osteoconductivity, has played an important role in bone tissue regeneration. However, it is difficult to prepare MBG scaffolds with high compressive strength for applications in bone regeneration; this difficulty has greatly hindered its development and use. To solve this problem, a simple powder processing technique has been successfully developed to fabricate a novel type of MBG scaffold (MBGS). Furthermore, amino or carboxylic groups could be successfully grafted onto MBGSs (denoted as N-MBGS and C-MBGS, respectively) through a post-grafting process. It was revealed that both MBGS and the functionalized MBGSs could significantly promote the proliferation and osteogenic differentiation of bMSCs. Due to its positively charged surface, N-MBGS presented the highest in vitro osteogenic capability of the three samples. Moreover, in vivo testing results demonstrated that N-MBGS could promote higher levels of bone regeneration compared with MBGS and C-MBGS. In addition to its surface characteristics, it is believed that the decreased degradation rate of N-MBGS plays a vital role in promoting bone regeneration. These findings indicate that MBGSs are promising materials with potential practical applications in bone regeneration, which can be successfully fabricated by combining a powder processing technique and post-grafting process.

Evaluation of in vivo angiogenetic effects of copper doped bioactive glass scaffolds in the AV loop model

Abstracteffects of 3D scaffolds made from 45S5 bioactive glass (BG) doped with 1 wt. % copper ions in the arteriovenous loop model of the rat.Materials and Methods: An arteriovenous loop was built in the groin of 10 rats and inserted in 1% copper doped 45S5 BG scaffolds and fibrin. The scaffold and the AV loop were inserted in Teflon isolation chambers and explanted 3 weeks after implantation. Afterwards the scaffolds were analyzed by Micro-CT and histology regarding vascularization. Results were compared to plain 45S5 BG-based scaffolds from a previous study.Results: Micro-CT and histological evaluation showed consistent vascularization of the constructs. A tendency towards an increased vascularization in the copper doped BG group compared to plain BG constructs could be observed. However, therewas no significant difference in statistical analysis between both groups.Conclusions: This study shows results that support an increased angiogenetic effect of 1% copper doped 45S5 BG compared to regular 45S5 BG scaffolds in the rat arteriovenous loop model although these tendencies are not backed by statistical evidence. Maybe higher copper doses could lead to a statistically significant angiogenetic effect.

Functionalized mesoporous bioactive glass scaffolds for enhanced bone tissue regeneration

Event Abstract Back to Event Functionalized mesoporous bioactive glass scaffolds for enhanced bone tissue regeneration Deliang Zeng1 and Xinquan Jiang1 1 The Ninth People’s Hospital affiliated to Shanghai Jiao Tong University, School of Mediceine, Department of Prosthodontics, China Introduction: Mesoporous bioactive glass (MBG), which possesses excellent bioactivity and biocompatibility, has played an important role in bone tissue regeneration. However, it is difficult to prepare MBG scaffolds with sufficient compressive strength for bone regeneration, which greatly hinder its development and applications. Materials and Methods: a simple powder processing technique has been successfully developed to fabricate a novel kind of MBG scaffolds (MBGS). The resultant MBGS not only possesses higher compressive strength up to 0.3 MPa and interconnected macro- structure with pore diameter of 100-300 μm, but also inherits the highly ordered mesoporous structure from MBG. Furthermore, amino or carboxylic groups could be successfully grafted (donated as N-MBGS and C-MBGS, respectively) through a post-grafting process. Results and Discussion: It is revealed that both MBGS and functionalized MBGSs could significantly promote the proliferation and osteogenic differentiation of bone marrow stromal cells (bMSCs) by improving their bone-related gene expression (runt-related transcription factor 2 (runx2), alkaline phosphatase (ALP), bone sialoprotein (BSP) and osteocalcin (OCN)). Due to the positively charged surface, N-MBGS presented the highest in vitro osteogenic capability among three samples. Moreover, the in vivo testing results in a rabbit femur defect model demonstrated that N-MBGS could result in more bone regeneration, in comparison with MBGS and C-MBGS. In addition to the surface characteristics, it is believed that the decreased degradation rate of N-MBGS plays a vital role in the bone regeneration. Conclusions: MBGS modified with amino groups not only provided suitable surface for cell to proliferate and differentiate, but also decreased the degradation rate to adapt new bone formation. And the novel surface characteristics of N-MBGS combined with bMSCs exhibited the largest newly formed bone area in the rabbit femur defects model. These indicate that the N-MBGS scaffold facilely fabricated by combining the powder processing technique has practical application potentials for bone regeneration. Figure 1: Effective scaffold system for enhanced bone regeneration. Figure 2: (A) Digital microscopic photograph, (B) Reverse color photograph, (C) SEM image and (D) SEM image in high magnification of MBGS, E) The compressive strength and porosity of MBGS and the contrast. (*MBG scaffolds prepared by the polyurethane foam template method) Figure 3: The color images represent sequential fluorescent labeling of AL, CA and the cross sections of rabbit femurs implanted (Histological observation of new bone formation in three kinds of scaffolds after 12 weeks). We thank Pro. Yongsheng Li and PhD. Xingdi Zhang for their involvement in the present study. And this work was financially supported by the 973 Program (Grant No. 2012CB933600); the National Natural Science Foundation of China (Grant Nos. 81300853)

O-Acrylamidomethyl-2-hydroxypropyltrimethyl ammonium chloride chitosan and silk modified mesoporous bioactive glass scaffolds with excellent mechanical properties, bioactivity and long-lasting antibacterial activity

Mesoporous bioactive glass (MBG) is a promising scaffold in bone tissue engineering because its large specific surface area facilitates bioactive behavior and allows mesopores to be loaded with osteogenic agents for promoting the formation of new bone. In the present study, a biocompatible MBG-based scaffold for bone regeneration applications with long-lasting antibacterial activity were fabricated via surface modification with O-acrylamidomethyl-2-hydroxypropyltrimethyl ammonium chloride chitosan (NMA-HACC) and silk. The NMA-HACC–silk (NHS) modified MBG scaffolds were prepared by evaporation-induced self-assembly using polyurethane sponges and the P123 surfactant as co-templates. The microstructure of the scaffold was characterized using scanning electron microscopy (SEM) and synchrotron radiation microcomputer tomography (SRμCT). Fourier transform infrared spectroscopy (FTIR), SEM, X-ray diffraction (XRD), and mechanical experiments were used to analyze the product's composition, inner microstructure, morphology, and mechanical strength before and after its surface modification. These methods were also used to assess the degree to which minerals became deposited on the scaffold after soaking in simulated body fluid (SBF). Confocal laser scanning microscopy (CLSM) was used to evaluate the antibacterial properties and biocompatibility of the scaffolds at various time intervals. Finally, biocompatibility was demonstrated by studying the in vitro proliferation and viability of human mesenchymal stem cells (hMSCs). The results showed that the fabricated scaffolds possessed well-ordered, three-dimensional structures and the NMA-HACC–silk modification rendered the pore network more uniform and continuous, leading to the significant improvement in bioactivity and in hMSC attachment, cell spreading and cell proliferation. Furthermore, the NMA-HACC–silk modification significantly prolonged the antibacterial activity of the MBG scaffold.

Facile production of porous bioactive glass scaffolds by the foam replica technique combined with sol–gel/electrophoretic deposition

3D porous bioactive glass (BG) scaffolds were fabricated by the foam replication technique combining sol–gel and electrophoretic deposition (EPD) processes. A special EPD set-up was built to optimize the scaffolds fabrication, which results in the rapid production of BG-based scaffolds in comparison to the traditional time-consuming foam replication technique normally used for the same kind of BG scaffolds. The influences of parameters related to the BG sol (aging time) as well as to the electrically driven process (deposition voltage) were studied and discussed in terms of the final scaffolds microstructure. Bioactivity of the samples, in terms of hydroxycarbonate apatite (HCA) formation in simulated body fluid (SBF), was determined after 1 day of immersion in SBF, confirming the suitability of the new scaffolds for bone regeneration applications.

Bioinspired trimodal macro/micro/nano-porous scaffolds loading rhBMP-2 for complete regeneration of critical size bone defect

Critical size bone defects raise great demands for efficient bone substitutes. Mimicking the hierarchical porous architecture and specific biological cues of natural bone has been considered as an effective strategy to facilitate bone regeneration. Herein, a trimodal macro/micro/nano-porous scaffold loaded with recombinant human bone morphogenetic protein-2 (rhBMP-2) was developed. With mesoporous bioactive glass (MBG) as matrix, a trimodal MBG scaffold (TMS) with enhanced compressive strength (4.28MPa, porosity of 80%) was prepared by a “viscosity controlling” and “homogeneous particle reinforcing” multi-template process. A 7.5nm, 3D cubic (Im3m) mesoporous structure was tailored for a “size-matched entrapment” of rhBMP-2 to achieve sustained release and preserved bioactivity. RhBMP-2-loaded TMS (TMS/rhBMP-2) induced excellent cell attachment, ingrowth and osteogenesis in vitro. Further in vivo ectopic bone formation and orthotopic rabbit radius critical size defect results indicated that compared to the rhBMP-2-loaded bimodal macro/micro- and macro/nano-porous scaffolds, TMS/rhBMP-2 exhibited appealing bone regeneration capacity. Particularly, in critical size defect, complete bone reconstruction with rapid medullary cavity reunion and sclerotin maturity was observed on TMS/rhBMP-2. On the basis of these results, TMS/rhBMP-2 developed here represents a promising bone substitute for clinical application and the concepts proposed in this study might provide new thoughts on development of future orthopedic biomaterials. Statement of SignificanceLimited self-regenerating capacity of human body makes the reconstruction of critical size bone defect a significant challenge. Current bone substitutes often exhibit undesirable therapeutic efficacy due to poor osteoconductivity or low osteoinductivity. Herein, TMS/rhBMP-2, an advanced mesoporous bioactive glass (MBG) scaffold with osteoconductive trimodal macro/micro/nano-porosity and osteoinductive rhBMP-2 delivery was developed. The preparative and mechanical problems of hierarchical MBG scaffold were solved without affecting its excellent biocompatibilities, and rhBMP-2 immobilization in sizematched mesopores was first explored. Combining structural and biological cues, TMS/rhBMP-2 achieved a complete regeneration with rapid medullary cavity reunion and sclerotin maturity in rabbit radius critical size defects. The design conceptions proposed in this study might provide new thoughts on development of future orthopedic biomaterials.