Scaffolds For Bone Tissue Regeneration Research Articles

A Biomimetic Platelet-Rich Plasma-Based Interpenetrating Network Printable Hydrogel for Bone Regeneration.

Repair of bone defects caused by trauma or diseases is the primary focus of prosthodontics. Hydrogels are among the most promising candidates for bone tissue regeneration due to their unique features such as excellent biocompatibility, similarities to biological tissues, and plasticity. Herein, we developed a type of novel biomimetic interpenetrating polymeric network (IPN) hydrogel by combining methacrylated alginate and 4-arm poly (ethylene glycol)-acrylate (4A-PEGAcr) through photo-crosslinking. Platelet-rich plasma (PRP), a patient-specific source of autologous growth factors, was incorporated into the hydrogel, and thereafter the hydrogels were biological mineralized by simulated body fluid (SBF). Physical properties of hydrogels were comprehensively characterized. In vitro studies demonstrated that the incorporation of PRP and biomineralization promoted the biocompatibility of hydrogel. Strikingly, the osteogenic bioactivities, including ALP activity, mineralized nodule formation, and expression of osteogenic markers were found substantially enhanced by this biomineralized PRP-hydrogel. Finally, a rabbit model of bone defect was employed to assess in vivo bone regeneration, micro-CT analysis showed that the biomineralized PRP-hydrogels could significantly accelerate bone generation. We believed that this novel biomineralized PRP-incorporated IPN hydrogel could be promising scaffolds for bone tissue regeneration.

Green synthesis of strontium-reduced graphene oxide biocomposite using gamma radiation

This study presents an environmentally benign approach for synthesizing of strontium nanoparticles-decorated reduced graphene oxide (rGO-Sr) nanosheets using a simple method. Reduced graphene oxide sheets decorated with strontium nanoparticles (rGO-Sr) were used in previous studies in polymer matrices to prepare 3D scaffolds for bone tissue regeneration. Graphene oxide is reduced and strontium nanoparticles have been successfully deposited on it using gamma radiation at room temperature. High-resolution transmission electron microscopy (HR-TEM) analysis assured the formation of strontium nanoparticles (Sr NPs) of 50 nm in size on reduced graphene oxide (rGO) nanosheets. The formed Sr NPs were homogeneously and uniformly distributed on rGO nanosheets forming rGO-Sr nanocomposite. The prepared materials' blood biocompatibility and antibacterial activities against Staphylococcus aureus were studied. The results revealed that the decoration of rGO sheets with strontium nanoparticles offered a significant increase in its antibacterial activity and exhibited good blood biocompatibility. This study shows that graphene-based composite prepared using Sr NPs seems to be a promising antibacterial coating material for biomedical applications.

Additive Manufacturing of Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/Poly(D,L-lactide-co-glycolide) Biphasic Scaffolds for Bone Tissue Regeneration.

Polyhydroxyalkanoates are biopolyesters whose biocompatibility, biodegradability, environmental sustainability, processing versatility, and mechanical properties make them unique scaffolding polymer candidates for tissue engineering. The development of innovative biomaterials suitable for advanced Additive Manufacturing (AM) offers new opportunities for the fabrication of customizable tissue engineering scaffolds. In particular, the blending of polymers represents a useful strategy to develop AM scaffolding materials tailored to bone tissue engineering. In this study, scaffolds from polymeric blends consisting of poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) and poly(D,L-lactide-co-glycolide) (PLGA) were fabricated employing a solution-extrusion AM technique, referred to as Computer-Aided Wet-Spinning (CAWS). The scaffold fibers were constituted by a biphasic system composed of a continuous PHBV matrix and a dispersed PLGA phase which established a microfibrillar morphology. The influence of the blend composition on the scaffold morphological, physicochemical, and biological properties was demonstrated by means of different characterization techniques. In particular, increasing the content of PLGA in the starting solution resulted in an increase in the pore size, the wettability, and the thermal stability of the scaffolds. Overall, in vitro biological experiments indicated the suitability of the scaffolds to support murine preosteoblast cell colonization and differentiation towards an osteoblastic phenotype, highlighting higher proliferation for scaffolds richer in PLGA.

Bioactive Cellulose Acetate Electrospun Mats as Scaffolds for Bone Tissue Regeneration.

In the last decades, cell-based approaches for bone tissue engineering (BTE) have relied on using models that cannot replicate the complexity of the bone microenvironment. There is an ongoing amount of research on scaffold development responding to the need for feasible materials that can mimic the bone extracellular matrix (ECM) and aid bone tissue regeneration (BTR). In this work, a porous cellulose acetate (CA) fiber mat was developed using the electrospinning technique and the mats were chemically modified to bioactivate their surface and promote osteoconduction and osteoinduction. The mats were characterized using FTIR and SEM/EDS to validate the chemical modifications and assess their structural integrity. By coupling adhesive peptides KRSR, RGD, and growth factor BMP-2, the fiber mats were bioactivated, and their induced biological responses were evaluated by employing immunocytochemical (ICC) techniques to study the adhesion, proliferation, and differentiation of premature osteoblast cells (hFOB 1.19). The biological assessment revealed that at short culturing periods of 48 hours and 7 days, the presence of the peptides was significant for proliferation and adhesion, whereas at longer culture times of 14 days, it had no significant effect on differentiation and maturation of the osteogenic progenitor cells. Based on the obtained results, it is thus concluded that the CA porous fiber mats provide a promising surface morphology that is both biocompatible and can be rendered bioactive upon the addition of osteogenic peptides to favor osteoconduction leading to new tissue formation.

Novel 3D Bioglass Scaffolds for Bone Tissue Regeneration.

The design of scaffolds with optimal biomechanical properties for load-bearing applications is an important topic of research. Most studies have addressed this problem by focusing on the material composition and not on the coupled effect between the material composition and the scaffold architecture. Polymer–bioglass scaffolds have been investigated due to the excellent bioactivity properties of bioglass, which release ions that activate osteogenesis. However, material preparation methods usually require the use of organic solvents that induce surface modifications on the bioglass particles, compromising the adhesion with the polymeric material thus compromising mechanical properties. In this paper, we used a simple melt blending approach to produce polycaprolactone/bioglass pellets to construct scaffolds with pore size gradient. The results show that the addition of bioglass particles improved the mechanical properties of the scaffolds and, due to the selected architecture, all scaffolds presented mechanical properties in the cortical bone region. Moreover, the addition of bioglass indicated a positive long-term effect on the biological performance of the scaffolds. The pore size gradient also induced a cell spreading gradient.

Methods of producing three dimensional electrospun scaffolds for bone tissue engineering: A review.

Bone is a dynamic, living tissue that exists and renews itself continuously in a 3D manner. Nevertheless, complex clinical conditions require a bone substitute to replace the defective bone and/or accelerate bone healing. Bone tissue engineering aims to treat bone defects that fail to heal on their own. Electrospinning provides an opportunity to create nano- to micro-fibrous scaffolds that mimic the architecture of the natural extracellular matrix (ECM) with high porosity and large specific surface area. Despite these advantages, traditional electrospun meshes can only provide a 2D architecture for cell attachment and proliferation rather than the 3D attachment in native tissue. Fabrication of 3D electrospun scaffolds for bone tissue regeneration is a challenging task, which has attracted significant attention over the past couple of decades. This review highlights recent strategies used to produce 3D electrospun/co-electrospun scaffolds for bone tissue applications describing the materials and procedures. It also considers combining conventional and coaxial electrospinning with other scaffold manufacturing techniques to produce 3D structures which have the potential to engineer missing bone in the human body.Graphical abstract[Formula: see text].

Engineering biomaterials to 3D-print scaffolds for bone regeneration: practical and theoretical consideration.

There are more than 2 million bone grafting procedures performed annually in the US alone. Despite significant efforts, the repair of large segmental bone defects is a substantial clinical challenge which requires bone substitute materials or a bone graft. The available biomaterials lack the adequate mechanical strength to withstand the static and dynamic loads while maintaining sufficient porosity to facilitate cell in-growth and vascularization during bone tissue regeneration. A wide range of advanced biomaterials are being currently designed to mimic the physical as well as the chemical composition of a bone by forming polymer blends, polymer-ceramic and polymer-degradable metal composites. Transforming these novel biomaterials into porous and load-bearing structures via three-dimensional printing (3DP) has emerged as a popular manufacturing technique to develop engineered bone grafts. 3DP has been adopted as a versatile tool to design and develop bone grafts that satisfy porosity and mechanical requirements while having the ability to form grafts of varied shapes and sizes to meet the physiological requirements. In addition to providing surfaces for cell attachment and eventual bone formation, these bone grafts also have to provide physical support during the repair process. Hence, the mechanical competence of the 3D-printed scaffold plays a key role in the success of the implant. In this review, we present various recent strategies that have been utilized to design and develop robust biomaterials that can be deployed for 3D-printing bone substitutes. The article also reviews some of the practical, theoretical and biological considerations adopted in the 3D-structure design and development for bone tissue engineering.

Hybrid scaffolds with a 3D-printed polymer lattice core and a bioactive hydrogel shell for bone regeneration

Recent research in the field of tissue engineering is focusing on the realization of hybrid scaffolds as multi-material systems which allow to successfully combine the advantages of different biomaterials. In addition, additive manufacturing technologies are currently explored for their production, as means to control and personalize the scaffold structure. In this paper, composite scaffolds with a core–shell structure are studied, the core consisting of a rigid poly-l-lactic acid lattice realized by fused deposition modeling, and the shell consisting of a bioactive hydrogel, grafted upon the core and freeze-dried to develop porous microstructure. Different lattice structures are designed and realized as repetition of unit cells having different size and strut arrangement. Compression tests reveal the suitability of the mechanical properties of the scaffolds for bone tissue regeneration, and the possibility to modulate their stiffness and strength upon the lattice parameters. Moreover, the interconnected porous structure of the shell, assessed by morphological analysis at the microscope, may promote cell colonization and proliferation, while its composition may support osteogenic differentiation.

An investigation into the viscoelastic response of chemically and physically crosslinked minimally invasive hydrogel scaffolds

We report development of injectable hydrogels as scaffolds for bone tissue regeneration. An integrated approach has been used to develop the bone scaffolds using nanocellulose (NC), synthesized from agricultural biomass, and poly(vinyl alcohol) (PVA). PVA based hydrogel was formed using physical crosslinking process involving multiple freeze–thaw cycles, while, NC based hydrogel was developed using chemical crosslinking mechanism in which epichlorohydrin was used as a crosslinker. Investigation of micro-structural surface topology was carried out using scanning electron microscopy which indicated favourable environment for cell adhesion. The viscoelastic response characterized using frequency, amplitude and temperature sweeps, demonstrated that within the experimental range, dynamic storage modulus (G’) was considerably higher than dynamic loss modulus (G’’) for all the hydrogel samples, indicating the formation of well-developed network and in turn structural integrity and dynamic stability of the injectable hydrogel scaffolds. Further, the injectable hydrogels demonstrated excellent injectability and self-standing behavior.

3D Printed SiOC(N) Ceramic Scaffolds for Bone Tissue Regeneration: Improved Osteogenic Differentiation of Human Bone Marrow-Derived Mesenchymal Stem Cells.

Bone tissue engineering has developed significantly in recent years as there has been increasing demand for bone substitutes due to trauma, cancer, arthritis, and infections. The scaffolds for bone regeneration need to be mechanically stable and have a 3D architecture with interconnected pores. With the advances in additive manufacturing technology, these requirements can be fulfilled by 3D printing scaffolds with controlled geometry and porosity using a low-cost multistep process. The scaffolds, however, must also be bioactive to promote the environment for the cells to regenerate into bone tissue. To determine if a low-cost 3D printing method for bespoke SiOC(N) porous structures can regenerate bone, these structures were tested for osteointegration potential by using human mesenchymal stem cells (hMSCs). This includes checking the general biocompatibilities under the osteogenic differentiation environment (cell proliferation and metabolism). Moreover, cell morphology was observed by confocal microscopy, and gene expressions on typical osteogenic markers at different stages for bone formation were determined by real-time PCR. The results of the study showed the pore size of the scaffolds had a significant impact on differentiation. A certain range of pore size could stimulate osteogenic differentiation, thus promoting bone regrowth and regeneration.

Surface Decoration of Redox-Modulating Nanoceria on 3D-Printed Tissue Scaffolds Promotes Stem Cell Osteogenesis and Attenuates Bacterial Colonization.

Oxidative stress at the bone defect site delays the bone regeneration process. Increased level of reactive oxygen species (ROS) is the primary cause of oxidative stress at the damaged site. Bone tissue scaffolds that scavenge ROS offer a potential and yet unexplored route for faster bone healing. Cerium oxide (ceria) is known for its redox-modulating behavior. Three-dimensional (3D)-printed porous scaffolds fabricated from degradable polymers provide a physical microenvironment but lack the bioactivity for tissue regeneration. In this work, porous poly(lactic acid) (PLA) scaffolds were prepared by 3D printing and modified with poly(ethylene imine) and citric acid to decorate with ceria nanoparticles. Scanning electron micrographs revealed a macroporous architecture decorated with ceria particles. The compressive modulus of 27 MPa makes them suitable for trabecular bone. The scaffolds supported human mesenchymal stem cell growth, confirming cytocompatibility. The ability to scavenge ROS confirmed that surface functionalization with ceria could reduce oxidative stress levels in the cells. Stem cell osteogenesis was enhanced after ceria decoration of the PLA scaffolds. Transcriptional profiling studied by sequencing revealed changes in the expression of genes associated with inflammation and cell-material interactions. The ceria-functionalized scaffolds show enhanced antibacterial activity against both Gram-negative and Gram-positive bacterial strains. These results demonstrate that surface decoration with nanoceria offers a viable route for enhancing the bioactivity of 3D-printed PLA scaffolds for bone tissue regeneration with ROS scavenging and antibacterial capability.

Comparative Study of Crystallization, Mechanical Properties, and In Vitro Cytotoxicity of Nanocomposites at Low Filler Loadings of Hydroxyapatite for Bone-Tissue Engineering Based on Poly(l-lactic acid)/Cyclo Olefin Copolymer.

A poly(l-lactic acid)/nanohydroxyapatite (PLLA/nHA) scaffold works as a bioactive, osteoconductive scaffold for bone-tissue engineering, but its low degradation rate limits embedded HA in PLLA to efficiently interact with body fluids. In this work, nano-hydroxyapatite (nHA) was added in lower filler loadings (1, 5, 10, and 20 wt%) in a poly(l-lactic acid)/cyclo olefin copolymer10 wt% (PLLA/COC10) blend to obtain novel poly(l-lactic acid)/cyclo olefin copolymer/nanohydroxyapatite (PLLA/COC10-nHA) scaffolds for bone-tissue regeneration and repair. Furthermore, the structure-activity relationship of PLLA/COC10-nHA (ternary system) nanocomposites in comparison with PLLA/nHA (binary system) nanocomposites was systematically studied. Nanocomposites were evaluated for structural (morphology, crystallization), thermomechanical properties, antibacterial potential, and cytocompatibility for bone-tissue engineering applications. Scanning electron microscope images revealed that PLLA/COC10-nHA had uniform morphology and dispersion of nanoparticles up to 10% of HA, and the overall nHA dispersion in matrix was better in PLLA/COC10-nHA as compared to PLLA/nHA. Fourier transformation infrared spectroscopy (FTIR), powder X-ray diffraction (XRD), and differential scanning calorimetry (DSC) studies confirmed miscibility and transformation of the α-crystal form of PLLA to the ά-crystal form by the addition of nHA in all nanocomposites. The degree of crystallinity (%) in the case of PLLA/COC10-nHA 10 wt% was 114% higher than pure PLLA/COC10 and 128% higher than pristine PLLA, indicating COC and nHA are acting as nucleating agents in the PLLA/COC10-nHA nanocomposites, causing an increase in the degree of crystallinity (%). Moreover, PLLA/COC10-nHA exhibited 140 to 240% (1–20 wt% HA) enhanced mechanical properties in terms of ductility as compared to PLLA/nHA. Antibacterial activity results showed that 10 wt% HA in PLLA/COC10-nHA showed substantial activity against P. aeruginosa, S. aureus, and L. monocytogenes. In vitro cytocompatibility of PLLA/COC10 and PLLA nanocomposites with nHA osteoprogenitor cells (MC3T3-E1) and bone mesenchymal stem cells (BMSC) was evaluated. Both cell lines showed two- to three-fold enhancement in cell viability and 10- to 30-fold in proliferation upon culture on PLLA/COC10-nHA as compared to PLLA/nHA composites. It was observed that the ternary system PLLA/COC10-nHA had good dispersion and interfacial interaction resulting in improved thermomechanical and enhanced osteoconductive properties as compared to PLLA/nHA.

New Bone Formation in the Whole Decellularized Cortical Bone Scaffold Using the Model of Revitalizing a Haversian System.

Decellularized allogeneic bone chips act as scaffolds for bone tissue regeneration. Owing to their lack of osteogenic potentials compared to autologous bone graft, decellularized bone scaffolds (DBSs) have applied only to small partial bone defects in clinical settings. Furthermore, only decellularized cancellous bone chips have been limitedly used for the purpose of bone regeneration. The cortical bone has less porosity and less osteogenic materials such as bone morphogenetic proteins in comparison with cancellous bone. In this study, we tried to accelerate new bone formation within the decellularized cortical bone scaffold using a vascular pedicle as an in vivo bioreactor.Forty DBSs were divided into 4 groups with different conditionings (DBS+ demineralized bone matrix [DBM], DBS+DBM+me+mesenchymal stem cells, DBS+DBM+vascular pedicle, and DBS+DBM+vascular pedicle+mesenchymal stem cells) and implanted into the back of 5 rabbits. Half of the DBSs were examined at 8 weeks and the other half at 16 weeks to determine vascularization level and osteogenesis within each group. New bone formation and bone-forming cells related to osteogenesis were observed via histological staining. Inclusion of the vascular pedicle resulted in larger areas of bone regeneration. With time, osteon structures became more prominent in groups containing the vascular pedicle.In summary, vascularized DBSs combined with a vascular pedicle have shown promising results for bone regeneration, thereby representing potential therapeutic alternatives for autologous bone grafts or bone tissue free transfer in large or segmental bone defects. In addition, demineralized whole cortical bone matrix along with vascular pedicle and various bone inductive materials, such as DBM and recombinant human bone morphogenetic protein-2, may be an additional new option of an ideal osteoinductive system.

Silver Decorated βTCP-Poly(3hydroxybutyrate) Scaffolds for Bone Tissue Engineering.

Implantations in orthopedics are associated with a high risk of bacterial infections in the surgery area. Therefore, biomaterials containing antibacterial agents, such as antibiotics, bactericidal ions or nanoparticles have been intensively investigated. In this work, silver decorated β tricalcium phosphate (βTCP)-based porous scaffolds were obtained and coated with a biopolymer—poly(3-hydroxybutyrate)-P(3HB). To the best of our knowledge, studies using silver-doped βTCP and P(3HB), as a component in ceramic-polymer scaffolds for bone tissue regeneration, have not yet been reported. Obtained materials were investigated by high-temperature X-ray diffraction, X-ray fluorescence, scanning electron microscopy with energy dispersive spectroscopy, hydrostatic weighing, compression tests and ultrahigh-pressure liquid chromatography with mass spectrometry (UHPLC-MS) measurements. The influence of sintering temperature (1150, 1200 °C) on the scaffolds’ physicochemical properties (phase and chemical composition, microstructure, porosity, compressive strength) was evaluated. Materials covered with P(3HB) possessed higher compressive strength (3.8 ± 0.6 MPa) and surgical maneuverability, sufficient to withstand the implantation procedures. Furthermore, during the hydrolytic degradation of the composite material not only pure (R)-3-hydroxybutyric acid but also its oligomers were released which may nourish surrounding tissues. Thus, obtained scaffolds were found to be promising bone substitutes for use in non-load bearing applications

Size Effects in Finite Element Modelling of 3D Printed Bone Scaffolds Using Hydroxyapatite PEOT/PBT Composites

Additive manufacturing (AM) of scaffolds enables the fabrication of customized patient-specific implants for tissue regeneration. Scaffold customization does not involve only the macroscale shape of the final implant, but also their microscopic pore geometry and material properties, which are dependent on optimizable topology. A good match between the experimental data of AM scaffolds and the models is obtained when there is just a few millimetres at least in one direction. Here, we describe a methodology to perform finite element modelling on AM scaffolds for bone tissue regeneration with clinically relevant dimensions (i.e., volume > 1 cm3). The simulation used an equivalent cubic eight node finite elements mesh, and the materials properties were derived both empirically and numerically, from bulk material direct testing and simulated tests on scaffolds. The experimental validation was performed using poly(ethylene oxide terephthalate)-poly(butylene terephthalate) (PEOT/PBT) copolymers and 45 wt% nano hydroxyapatite fillers composites. By applying this methodology on three separate scaffold architectures with volumes larger than 1 cm3, the simulations overestimated the scaffold performance, resulting in 150–290% stiffer than average values obtained in the validation tests. The results mismatch highlighted the relevance of the lack of printing accuracy that is characteristic of the additive manufacturing process. Accordingly, a sensitivity analysis was performed on nine detected uncertainty sources, studying their influence. After the definition of acceptable execution tolerances and reliability levels, a design factor was defined to calibrate the methodology under expectable and conservative scenarios.

Biomechanical performances of PCL/HA micro- and macro-porous lattice scaffolds fabricated via laser powder bed fusion for bone tissue engineering

The present experimental study aims to extend know-how on resorbable polycaprolactone/hydroxyapatite (PCL/HA, 70/30 wt%) scaffolds, produced by Laser Powder Bed Fusion (LPBF) technology, to geometrically complex lattice structures and micro porous struts. Using optimized LPBF printing parameters, micro- and macro-porous scaffolds for bone tissue regeneration were produced by regularly repeating in space Diamond (DO) and Rhombic Dodecahedron (RD) elementary unit cells. After production, scaffolds were submitted to structural, mechanical, and biological characterization. The interaction of scaffolds with human Mesenchymal Stem Cells (hMSCs) allowed studying the degradative processes of the PCL matrix. Biomechanical performances and biodegradation of scaffolds were compared to literature results and bone tissue data. Mechanical compression test, biological viability up to 4 days of incubation and degradation rate evidenced strong dependence of scaffold behavior on unit cell geometry as well as on global geometrical features.

Biodegradable Microparticles for Bone Tissue Regeneration Based on Polylactide and Hydroxyapatite Nanoparticles

The process of forming hybrid microparticles from a biodegradable polyester, that is, polylactide, and hydroxyapatite nanoparticles, which can be promising as cellular microcarriers or starting materials for obtaining three-dimensional scaffolds for bone tissue regeneration, has been investigated. A method has been developed for fabricating hybrid microparticles by evaporation of solvents from oil/water emulsions without the use of additional emulsifiers in a dispersion phase. It is shown that hydroxyapatite nanoparticles can effectively stabilize the interface during the preparation of microparticles. The effect of the concentration of hydroxyapatite nanoparticles and their preliminary dispersion using ultrasonic treatment on the yield of microparticles, their size distribution and morphology was evaluated.

Composite Scaffolds for Bone Tissue Regeneration Based on PCL and Mg-Containing Bioactive Glasses.

Simple SummaryPolycaprolactone (PCL) is a bioresorbable and biocompatible polymer that has been widely used in long-term implants. However, when it comes to regenerative medicine, PCL suffers from some shortcomings such as a slow degradation rate, poor mechanical properties, and low cell adhesion. The incorporation of ceramics such as bioactive glasses into the PCL matrix has yielded a class of hybrid biomaterials with remarkably improved mechanical properties, controllable degradation rates, and enhanced bioactivity, which are suitable for bone tissue engineering. The use of conventional approaches (such as solvent casting and particulate leaching, phase separation, electrospinning, freeze drying, etc.) in realizing these composite scaffolds strongly affects the control of both the internal and the external architecture of scaffolds, including pore size, pore morphology, and overall structure porosity. Accordingly, 3D printing was used in this study because of the benefits offered over conventional methods, such as high flexibility in shape and size, high reproducibility, capabilities of precise control over internal architecture down to the microscale level, and a customized design that can be tailored to specific patient needs. The optimization of the scaffold structure was previously investigated in terms of architecture through the combination of the Taguchi method and CAD drawing, and, in this study, it was investigated by varying the composition of the composite material.Polycaprolactone (PCL) is widely used in additive manufacturing for the construction of scaffolds for tissue engineering because of its good bioresorbability, biocompatibility, and processability. Nevertheless, its use is limited by its inadequate mechanical support, slow degradation rate and the lack of bioactivity and ability to induce cell adhesion and, thus, bone tissue regeneration. In this study, we fabricated 3D PCL scaffolds reinforced with a novel Mg-doped bioactive glass (Mg-BG) characterized by good mechanical properties and biological reactivity. An optimization of the printing parameters and scaffold fabrication was performed; furthermore, an extensive microtopography characterization by scanning electron microscopy and atomic force microscopy was carried out. Nano-indentation tests accounted for the mechanical properties of the scaffolds, whereas SBF tests and cytotoxicity tests using human bone-marrow-derived mesenchymal stem cells (BM-MSCs) were performed to evaluate the bioactivity and in vitro viability. Our results showed that a 50/50 wt% of the polymer-to-glass ratio provides scaffolds with a dense and homogeneous distribution of Mg-BG particles at the surface and roughness twice that of pure PCL scaffolds. Compared to pure PCL (hardness H = 35 ± 2 MPa and Young’s elastic modulus E = 0.80 ± 0.05 GPa), the 50/50 wt% formulation showed H = 52 ± 11 MPa and E = 2.0 ± 0.2 GPa, hence, it was close to those of trabecular bone. The high level of biocompatibility, bioactivity, and cell adhesion encourages the use of the composite PCL/Mg-BG scaffolds in promoting cell viability and supporting mechanical loading in the host trabecular bone.

Preparation of a PLGA-coated porous bioactive glass scaffold with improved mechanical properties for bone tissue engineering approaches

The study aimed to improve the mechanical properties of a sol-gel-derived bioactive glass (BG) foam scaffold by poly-lactic co-glycolic acid (PLGA) coating as a potential scaffold for bone tissue regeneration. Polyurethane (PU) foam as the initial frame was submerged into a sol-gel-derived BG solution. The heat treatment process was carried out at 450°C to remove the PU foam and 860°C to consolidate the glass and remove the nitrate groups. The prepared BG scaffolds then were submerged into 10 and 15 wt% of PLGA solution. The uncoated BG scaffold was characterized by DTA/TGA, XRD, SEM, and TEM. The PLGA-coated scaffolds were characterized using SEM, and the mean compressive strength of the samples was measured. The DTA/TGA and XRD pattern indicated the removal of all nitrate groups at the temperatures above 700°C and also crystallization of BG after 800°C. The mean compressive strength of 10% and 15% PLGA-coated scaffolds were obtained 1.36±0.39 and 1.95±0.70 MPa, respectively, while the uncoated samples were crushed before the test. The SEM images exhibited that in the coated samples, the BG struts were covered with a PLGA layer and the coated layer was thicker in 15% PLGA samples. The SEM images also revealed that the PLGA coating maintained the structure of the broken struts and prevented them from coming apart. Thus, based on the obtained results, the PLGA coating was successfully toughened the BG scaffold and improved its elasticity. The study aimed to improve the mechanical properties of a sol-gel derived bioactive glass (BG) foam scaffold by Poly-lactic co-glycolic acid (PLGA) coating as a potential scaffold for bone tissue regeneration. Based on the results of this study, the PLGA coating can improve the elasticity and relieve the brittleness of sol-gel derived BG scaffold by supporting the fractured struts and prevent the scaffold from coming apart during a compressive strength test. Consequently, based on the obtained results a 15% PLGA-coated sol-gel derived BG scaffold can be considered as a potential scaffold for bone tissue regeneration.

An Elastic Mineralized 3D Electrospun PCL Nanofibrous Scaffold for Drug Release and Bone Tissue Engineering.

Complex shaped and critical-sized bone defects have been a clinical challenge for many years. Scaffold-based strategies such as hydrogels provide localized drug release while filling complex defect shapes, but ultimately possess weaknesses in low mechanical strength alongside a lack of macroporous and collagen-mimicking nanofibrous structures. Thus, there is a demand for mechanically strong, extracellular matrix (ECM) mimicking scaffolds that can robustly fit complex shaped critical sized defects and simultaneously provide localized, sustained, multiple growth factor release. We therefore developed a composite, bi-phasic PCL/hydroxyapatite (HA) 3D nanofibrous (NF) scaffold for bone tissue regeneration by using our innovative electrospun-based thermally induced self-agglomeration (TISA) technique. One intriguing feature of our ECM-mimicking TISA scaffolds is that they are highly elastic and porous even after evenly coated with minerals and can easily be pressed to fit different defect shapes. Furthermore, the bio-mimetic mineral deposition technique allowed us to simultaneously encapsulate different type of drugs, e.g., proteins and small molecules, on TISA scaffolds under physiologically mild conditions. Compared to scaffolds with physically surface-adsorbed phenamil, a BMP2 signaling agonist, incorporated phenamil composite scaffolds indicated less burst release and longer lasting sustained release of phenamil with subsequently improved osteogenic differentiation of cells in vitro. Overall, our study indicated that the innovative press-fit 3D NF composite scaffold may be a robust tool for multiple-drug delivery and bone tissue engineering.