Uncoated Scaffolds Research Articles

Magnesium oxide nanoparticle reinforced pumpkin-derived nanostructured cellulose scaffold for enhanced bone regeneration

Considering global surge in bone fracture prevalence, limitation in use of traditional healing approaches like bone grafts highlights the need for innovative regenerative strategies. Here, a novel green fabrication approach has reported for reinforcement of physicochemical performances of sustainable bioinspired extracellular matrix (ECM) based on decellularized pumpkin tissue coated with Magnesium oxide nanoparticles (hereafter called DM-Pumpkin) for enhanced bone regeneration. Compared to uncoated scaffold, DM-Pumpkin exhibited significantly improved surface roughness, mechanical stiffness, porosity, hydrophilicity, swelling, and biodegradation rate. Obtained nanoporous structure provides an ideal three-dimensional microenvironment for the attachment, migration and osteo-induction in human adipose-derived mesenchymal stem cells (h- AdMSCs). Calcium deposition and mineralization, alkaline phosphatase activity, and SEM imaging of the cells as well as increased expression of bone-related genes after 21 days incubation confirmed capability of DM-Pumpkin in mimicking the biological properties of bone tissue. The presence of MgONPs had a silencing effect on inflammatory factors and improved wound closure, verified by in vivo studies. Increased expression of collagen type I and osteocalcin in the h- AdMSCs cultured on DM-Pumpkin compared to control further corroborated gained results. Altogether, boosting physicochemical and biological properties of DM-Pumpkin due to surface modification is a promising approach for guided bone regeneration.

Investigating the Influence of Additive Manufacturing and Ultrasonic Coating Parameters on Biopolymeric Scaffold Performance Using Response Surface Methodology.

Triply periodic minimal surface (TPMS) scaffolds have gained attention in additive manufacturing due to their unique porous structures, which are useful in biomedical applications. Unlike metallic implants that can cause stress shielding, polymeric scaffolds offer a safer alternative. This study is focused on enhancing the compressive strength of additive-manufactured polylactic acid (PLA) scaffolds with a diamond structure. The response surface methodology (RSM)-based experimental design was developed to study the influence of printing parameters. The fused deposition modeling (FDM) process parameters were optimized, achieving a compressive strength of 56.2 MPa. Subsequently, the scaffolds were fabricated at optimized parameters and underwent ultrasonic-assisted polydopamine coating. With the utilization of the RSM approach, the study examined the effects of ultrasonic vibration power, coating solution concentration, and submersion time on compressive strength. The optimal coating conditions led to a maximum compressive strength of 92.77 MPa-a 65.1% improvement over the uncoated scaffold. This enhancement is attributed to the scaffold's porous structure, which enables uniform coating deposition. Energy-dispersive x-ray spectroscopy confirmed the successful polydopamine coating, with 10.64 wt% nitrogen content. These findings demonstrate the potential of ultrasonic-assisted coating in improving the mechanical properties of PLA scaffolds, making them suitable for biomedical applications.

3D Printing and Surface Engineering of Ti6Al4V Scaffolds for Enhanced Osseointegration in an In Vitro Study.

Ti6Al4V superalloy is recognized as a good candidate for bone implants owing to its biocompatibility, corrosion resistance, and high strength-to-weight ratio. While dense metal implants are associated with stress shielding issues due to the difference in densities, stiffness, and modulus of elasticity compared to bone tissues, the surface of the implant/scaffold should mimic the properties of the bone of interest to assure a good integration with a strong interface. In this study, we investigated the additive manufacturing of porous Ti6Al4V scaffolds and coating modification for enhanced osteoconduction using osteoblast cells. The results showed the successful fabrication of porous Ti6Al4V scaffolds with adequate strength. Additionally, the surface treatment with NaOH and Dopamine Hydrochloride (DOPA) promoted the formation of Dopamine Hydrochloride (DOPA) coating with an optimized coating process, providing an environment that supports higher cell viability and growth compared to the uncoated Ti6Al4V scaffolds, as demonstrated by the higher proliferation ratios observed from day 1 to day 29. These findings bring valuable insights into the surface modification of 3D-printed scaffolds for improved osteoconduction through the coating process in solutions.

Enhancing electrical conductivity and mechanical properties of decellularized umbilical cord arteries using graphene coatings.

Traditional decellularized bioscaffolds possessing intact vascular networks and unique architecture have been extensively studied as conduits for repairing nerve damage. However, they are limited by the absence of electrical conductivity, which is crucial for proper functioning of nervous tissue. This study focuses on investigating decellularized umbilical cord arteries by applying coatings of graphene oxide (GO) and reduced graphene oxide (RGO) to their inner surfaces. This resulted in a homogeneous GO coating that fully covered the internal lumen of the arteries. The results of electrical measurements demonstrated that the conductivity of the scaffolds could be significantly enhanced by incorporating RGO and GO conductive sheets. At a low frequency of 0.1 Hz, the electrical resistance level of the coated scaffolds decreased by 99.8% with RGO and 98.21% with GO, compared with uncoated scaffolds. Additionally, the mechanical properties of the arteries improved by 24.69% with GO and 32.9% with RGO after the decellularization process. The GO and RGO coatings did not compromise the adhesion of endothelial cells and promoted cell growth. The cytotoxicity tests revealed that cell survival rate increased over time with RGO, while it decreased with GO, indicating the time-dependent effect on the cytotoxicity of GO and RGO. Blood compatibility evaluations showed that graphene nanomaterials did not induce hemolysis but exhibited some tendency toward blood coagulation.

Additive manufacturing of polylactic acid scaffolds dip-coated with polycaprolactone for bone tissue engineering

Bone tissue engineering aims to create scaffolds that support bone regeneration, addressing the needs of approximately 1.71 billion people with bone structure problems worldwide. This study explores the fabrication and characterization of 3D-printed polylactic acid (PLA) scaffolds dip-coated with polycaprolactone (PCL), producing complex geometries with interconnected pores, specifically RoundBar Sphere and RoundBar Cube. The scaffolds were then coated with PCL solutions of 0.5 % and 1 % concentrations, applying up to three layers. Surface topology analysis indicated that PCL coating slightly reduced pore size (1150 µm to 900) while improving coverage and integrity. After coating, Fourier Transform Infrared Spectroscopy (FTIR) confirmed the presence of PCL on scaffold surfaces (characteristic bands at 1726, 1175 and 728 cm−1), whose a better coverage was obtained with more layers and higher concentrations of PCL. Coated scaffolds showed not significant change in compressive strengths (2–12 MPa), remaining suitable for trabecular bone applications. Hemolysis assays of the 3D scaffolds promoted non-hemolytic properties (0 % hemolysis), ensuring their blood compatibility. Metabolic activity (>70 %) and live/dead cell assays in human dermal fibroblasts (HDF) exhibited biocompatibilities for all samples, with coated scaffolds promoting enhanced cell proliferation compared to uncoated ones. Additionally, osteoblast metabolic activity (>90 %) and osteoblasts scratch assay demonstrated coated scaffolds promoted an area reduction of 1.36 and 1.53-fold higher than the control group and uncoated scaffold, respectively. In short, these coated scaffolds are promising candidates for bone tissue engineering and bone repair applications.

Sputtered zirconium based metallic glassy thin films onto electrospun PCL nanofibrous scaffolds for enriching bioactivity

Surface modification of electrospun Polycaprolactone (PCL) nanoscaffold is to enhance surface properties, particularly bioactivity. In this paper, electrospinning was employed to produce PCL nanoscaffolds and enhancing the bioactivity of the electrospun PCL scaffolds by sputtering of Zirconium based thin film metallic glasses (Zr -TFMGs). The Energy Dispersive Spectroscopy (EDS) analysis exhibited the presence of Zr, Ti and Si and surface topography by Atomic Force Microscopy (AFM) revealed the smooth surface of metallic glasses with nanofibrous structures. The sputtered samples were subjected to immersion test in Simulated Body Fluid (SBF) to analyze the apatite forming ability of Zr–Ti–Si metallic glasses. After 21days of incubation, SEM clearly showed the spherical structures of apatite formed on the surface of modified electrospun PCL. Cell viability studies using L929 fibroblast cells indicates the higher proliferation rate for the Zr based TFMG sputtered PCL scaffold specimen than the uncoated neat PCL scaffold and indicating the bioactive nature of Zr based TFMG. Contact angle of TFMG sputtered sample exhibited the hydrophobic surface which is helpful in preventing the biomedical devices from blood coagulation.

Electrospun polycaprolactone/graphene oxide scaffolds with secondary surface porosity and gelatin-coating

Polycaprolactone (PCL) is a versatile and biodegradable synthetic polymer widely used in tissue regeneration applications owing to its versatility and mechanical properties. In this study, we employed a three-level strategy to develop innovative PCL-based scaffold biomaterials using electrospinning. First, we incorporated graphene oxide (GO); second, we introduced secondary surface porosity (SSP) through non-solvent induced phase separation (NIPS) with a diameter of approximately 2 μm; and third, we applied a gelatin coating (Gt). The inclusion of GO resulted in both a reduction in fiber size and a decrease in the size of the secondary surface pores formed on the fibers. Additionally, the incorporation of GO led to a noteworthy 20-fold increase in gelatin adhesion compared to pure SSP-PCL scaffolds. However, the mechanical properties of the gelatin-coated scaffolds exhibited a decrease compared to the uncoated scaffolds. This reduction is primarily attributed to the decrease in crystallinity in coating gelatin scaffold. Furthermore, GO and gelatin played critical roles in enhancing biodegradation and bioactivity, promoting hydroxyapatite formation on the surface of SSP-PCL scaffolds. In vitro cell viability tests demonstrated the cytocompatibility of PCL, PCL/Gt, and PCL/Gt/GO electrospun SSP scaffolds, facilitating the adhesion of human mesenchymal stem cells. Our study introduces an innovative strategy for fabricating PCL scaffolds through electrospinning, incorporating SSP for improved gelatin adsorption, and holds great promise for tissue engineering applications.

Additive Manufacturing of Iron Carbide Incorporated Bioactive Glass Scaffolds for Bone Tissue Engineering and Drug Delivery Applications.

In this study, we have synthesized a bioactive glass with composition 45SiO2-20Na2O-23CaO-6P2O5-2.5B2O3-1ZnO-2MgO-0.5CaF2 (wt %). Further, it has been incorporated with 0.4 wt % iron carbide nanoparticles to prepare magnetic bioactive glass (MBG) with good heat generation capability for potential applications in magnetic field-assisted hyperthermia. The MBG scaffolds have been fabricated using extrusion-based additive manufacturing by mixing MBG powder with 25% Pluronic F-127 solution as the binder. The saturation magnetization of iron carbide nanoparticles in the bioactive glass matrix has been found to be 80 emu/g. The morphological analysis (pore size distribution, porosity, open pore network modeling, tortuosity, and pore interconnectivity) was done using an in-house developed methodology that revealed the suitability of the scaffolds for bone tissue engineering. The compressive strength (14.3 ± 1.6 MPa) of the MBG scaffold was within the range of trabecular bone. The in vitro test using simulated body fluid (SBF) showed the formation of apatite indicating the bioactive nature of scaffolds. Further, the drug delivery behaviors of uncoated and polycaprolactone (PCL) coated MBG scaffolds have been evaluated by loading an anticancer drug (Mitomycin C) onto the scaffolds. While the uncoated scaffold demonstrated the drug's burst release for the initial 80 h, the PCL-coated scaffold showed the gradual release of the drug. These results demonstrate the potential of the proposed MBG for bone tissue engineering and drug delivery applications.

Biological and Mechanical Response of Graphene Oxide Surface‐Treated Polylactic Acid 3D‐Printed Bone Scaffolds: Experimental and Numerical Approaches

Employing 3D printing bone scaffolds with various polymers is growing due to their biocompatibility, biodegradability, and good mechanical properties. However, their biological properties need modification to have fewer difficulties in clinical experiments. Herein, the fused‐deposition modeling technique is used to design triply‐periodic‐minimal‐surfaces polylactic‐acid scaffolds and evaluate their biological response under static and dynamic cell culture conditions. To enhance the biological response of 3D‐printed bone scaffolds, graphene‐oxide (GO) is coated on the surface of the scaffolds. Fourier‐transform infrared spectroscopy, X‐ray diffraction, and energy‐dispersion X‐ray analysis are conducted to check the GO presence and its effects. Also, computational fluid dynamics analysis is implemented to investigate the shear stress on the scaffold, which is a critical parameter for cell proliferation under dynamic cell culture conditions. Compression tests and contact‐angle measurements are performed to assess the GO effect on mechanical properties and wettability, respectively. Also, it was shown that surface‐treated scaffolds have lower mechanical properties and higher wettability than uncoated scaffolds. A perfusion bioreactor is used to study cell culture. Also, field‐emission‐scanning‐electron‐microscope and 3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5 diphenyl‐tetrazolium‐bromide (MTT) assay analyses are conducted to observe cell viability and cell attachment. An increase of up to 220% in viability was achieved with GO and dynamic cell culture.

Low cost structured photocatalysts from stereolithography of colorless pharmaceutical glass

The present study is dedicated to the manufacturing of highly porous triply periodic minimal surface (TPMS) constructs, fabricated from recycled end of life borosilicate pharmaceutical glass employing masked stereolithography. The structures were prepared from a simple blend of photocurable resin with glass powder (<38 µm). The gyroid model was selected with the porosity varying from 75 to 90%. Hot stage microscopy was applied to examine the glass sintering behaviour to improve the translucency of the 3D scaffolds. The obtained 3D scaffolds were dip-coated with TiO2 and further utilized for the photocatalytic degradation of dyes. The photocatalytic efficiency of the 3D scaffolds was evaluated by the degradation of methylene blue in water. It was found that 3D scaffolds coated with TiO2 showed a 40% higher degradation rate in comparison to bare 3D scaffolds under UV irradiation, which determines the significant role of TiO2 in the organic dye degradation. The better efficiency of 3D scaffolds coated with TiO2, compared with uncoated BSG 3D scaffolds is attributed to a better recombination rate, and the migration of electrons to the surface of the scaffold, where the charges participate in the photodecomposition of MB dye. The efficiency of the scaffolds was assessed for five consecutive cycles. The degradation efficiency after the fifth cycle was 75%, confirming the stability of the system.

Influence of polylactide coating stereochemistry on mechanical and in vitro degradation properties of porous bioactive glass scaffolds for bone regeneration.

The mechanical properties of polylactide stereocomplexes (PLA SC) have been primarily studied through tensile testing, with inconsistent results, and the compressive properties of PLA SC compared to homocrystalline or amorphous PLA remain poorly understood. In this study, we coated porous bioactive glass 13-93 scaffolds with amorphous, homocrystalline, or stereocomplex PLA to investigate their mechanical and degradation properties before and after immersion in simulated body fluid. The glass scaffolds had interconnected pores and an average porosity of 76%. The PLA coatings, which were 10-100 μm thick and approximately 3% of the glass scaffold mass, covered the glass to a large extent. The compressive strength and toughness of all PLA-coated scaffolds were significantly higher than those of uncoated scaffolds, with approximately a fourfold increase before immersion and a twofold increase after immersion. The compressive strength and toughness of PLA SC-coated scaffolds were similar to those of scaffolds with homocrystalline PLA coating, and significantly higher than for scaffolds with amorphous PLA coating. All PLA coatings moderated the initial pH increase caused by the glass, which could benefit surrounding cells and bone tissue in vivo after implantation.

Mechanical and Functional Improvement of β-TCP Scaffolds for Use in Bone Tissue Engineering.

Autologous bone transplantation is still considered as the gold standard therapeutic option for bone defect repair. The alternative tissue engineering approaches have to combine good hardiness of biomaterials whilst allowing good stem cell functionality. To become more useful for load-bearing applications, mechanical properties of calcium phosphate materials have to be improved. In the present study, we aimed to reduce the brittleness of β-tricalcium phosphate (β-TCP). For this purpose, we used three polymers (PDL-02, -02a, -04) for coatings and compared resulting mechanical and degradation properties as well as their impact on seeded periosteal stem cells. Mechanical properties of coated and uncoated β-TCP scaffolds were analyzed. In addition, degradation kinetics analyses of the polymers employed and of the polymer-coated scaffolds were performed. For bioactivity assessment, the scaffolds were seeded with jaw periosteal cells (JPCs) and cultured under untreated and osteogenic conditions. JPC adhesion/proliferation, gene and protein expression by immunofluorescent staining of embedded scaffolds were analyzed. Raman spectroscopy measurements gave an insight into material properties and cell mineralization. PDL-coated β-TCP scaffolds showed a significantly higher flexural strength in comparison to that of uncoated scaffolds. Degradation kinetics showed considerable differences in pH and electrical conductivity of the three different polymer types, while the core material β-TCP was able to stabilize pH and conductivity. Material differences seemed to have an impact on JPC proliferation and differentiation potential, as reflected by the expression of osteogenic marker genes. A homogenous cell colonialization of coated and uncoated scaffolds was detected. Most interesting from a bone engineer's point of view, the PDL-04 coating enabled detection of cell matrix mineralization by Raman spectroscopy. This was not feasible with uncoated scaffolds, due to intercalating effects of the β-TCP material and the JPC-formed calcium phosphate. In conclusion, the use of PDL-04 coating improved the mechanical properties of the β-TCP scaffold and promoted cell adhesion and osteogenic differentiation, whilst allowing detection of cell mineralization within the ceramic core material.

Development and Characterization of Non-coated and PLGA-Coated S53P4 and S59 Bioactive Glass Scaffolds for Treatment of Load-Bearing Defects

Abstract We studied how in vitro reactions affect long-term biochemical and mechanical properties of porous tissue engineering scaffolds based on two bioactive glasses and accordingly their potential suitability for treating critical-size load-bearing bone defects. Granules of bioactive glass S53P4 and S59 were used to sinter the porous scaffolds. The sintering variables for mechanically durable scaffolds were initially selected according to the thermal behaviour of the glasses during heating. The S53P4 and S59 scaffolds were further divided into the following three groups: uncoated scaffolds, poly(dl-lactide-co-glycolide) (PLGA) coated scaffolds, and scaffolds coated with a mixture of PLGA and powdered S53P4. The purpose of the coating is to enhance mechanical abilities and to induce a membrane rich in growth factors surrounding the BAG implant. Characterization of the scaffolds included water absorption, pH, ion release, reaction layer formation, and compressive strength. Polymer coatings with powdered S53P4 absorbed more water than pure polymer coatings. The pH of the immersion solution increased more upon immersion of the uncoated scaffolds. No marked differences were seen between the coated scaffolds. During the 28-day in vitro immersion, the Ca-ion concentration initially increased for non-coated S53P4 scaffolds, followed by a slight increase starting at 14 days for all S53P4-based scaffolds and S59-PLGA scaffolds. The lowest P species concentration was observed for uncoated S53P4 scaffolds. The polymer coatings hindered the dissolution of Si-species from the scaffolds. Thicker calcium phosphate layers were identified at the uncoated scaffolds, suggesting a higher bioactivity. In contrast, the polymer coatings enhanced the compressive strength of the scaffolds. The results reflect the impact of glass composition and polymer coating on the chemical and physical properties of scaffolds, emphasizing the requirements in clinical applications for critical load-bearing bone defects. Graphical Abstract

3D-printed biodegradable magnesium alloy scaffolds with zoledronic acid-loaded ceramic composite coating promote osteoporotic bone defect repair.

Osteoporotic fracture is one of the most serious complications of osteoporosis. Most fracture sites have bone defects, and restoring the balance between local osteogenesis and bone destruction is difficult during the repair of osteoporotic bone defects. In this study, we successfully fabricated three-dimensional (3D)-printed biodegradable magnesium alloy (Mg-Nd-Zn-Zr) scaffolds and prepared a zoledronic acid-loaded ceramic composite coating on the surface of the scaffolds. The osteogenic effect of Mg and the osteoclast inhibition effect of zoledronic acid were combined to promote osteoporotic bone defect repair. In vitro degradation and drug release experiments showed that the coating significantly reduced the degradation rate of 3D-printed Mg alloy scaffolds and achieved a slow release of loaded drugs. The degradation products of drug-loaded coating scaffolds can promote osteogenic differentiation of bone marrow mesenchymal stem cells as well as inhibit the formation of osteoclasts and the bone resorption by regulating the expression of related genes. Compared with the uncoated scaffolds, the drug-coated scaffolds degraded at a slower rate, and more new bone grew into these scaffolds. The healing rate and quality of the osteoporotic bone defects significantly improved in the drug-coated scaffold group. This study provides a new method for theoretical research and clinical treatment using functional materials for repairing osteoporotic bone defects.

Physical, mechanical, and biological performance of chitosan-based nanocomposite coating deposited on the polycaprolactone-based 3D printed scaffold: Potential application in bone tissue engineering

Recently, coating on composite scaffolds has attracted many researchers' attention to improve scaffolds' properties. In this research, a 3D printed scaffold was fabricated from polycaprolactone (PCL)/magnetic mesoporous bioactive glass (MMBG)/alumina nanowire (Al2O3, Optimal percentage 5 %) (PMA) and then coated with chitosan (Cs)/multi-walled carbon nanotubes (MWCNTs) by an immersion coating method. Structural analyses such as XRD and ATR-FTIR confirmed the presence of Cs and MWCNTs in the coated scaffolds. The SEM results of the coated scaffolds showed homogeneous three-dimensional structures with interconnected pores compared to the uncoated scaffolds. The coated scaffolds exhibited an increase in compression strength (up to 16.1 MPa) and compressive modulus (up to 40.83 MPa), improved surface hydrophilicity (up to 32.69°), and decrease in degradation rate (68 % remaining weight) compared to the uncoated scaffolds. The increase in apatite formation in the scaffold coated with Cs/MWCNTs was confirmed by SEM, EDAX, and XRD tests. Coating the PMA scaffold with Cs/MWCNTs leads to the viability and proliferation of MG-63 cells and more secretion of alkaline phosphatase and Ca activity, which can be introduced as a suitable candidate for use in bone tissue engineering.

Primary Human Ligament Fibroblast Adhesion and Growth on 3D-Printed Scaffolds for Tissue Engineering Applications

The current gold standard technique for the treatment of anterior cruciate ligament (ACL) injury is reconstruction with a tendon autograft. These treatments have a relatively high failure and re-rupture rate and are associated with early-onset osteoarthritis, developing within two decades of injury. Furthermore, both autografting and allografting come with several drawbacks. Tissue engineering and additive manufacturing present exciting new opportunities to explore 3D scaffolds as graft substitutes. We previously showed that 3D-printed scaffolds using low-cost equipment are suitable for tissue engineering approaches to regenerative medicine. Here, we hypothesize that Lay-Fomm 60, a commercially available nanoporous elastomer, may be a viable tissue engineering candidate for an ACL graft substitute. We first printed nanoporous thermoplastic elastomer scaffolds using low-cost desktop 3D printers and determined the mechanical and morphological properties. We then tested the impact of different surface coatings on primary human ACL fibroblast adhesion, growth, and ligamentous matrix deposition in vitro. Our data suggest that poly-L-lysine-coated Lay-Fomm 60 scaffolds increased ligament fibroblast activity and matrix formation when compared to uncoated scaffolds but did not have a significant effect on cell attachment and proliferation. Therefore, uncoated 3D printed Lay-Fomm 60 scaffolds may be viable standalone scaffolds and warrant further research as ligament tissue engineering and reconstruction grafts.

BMP-2 incorporated into a biomimetic coating on 3D-printed titanium scaffold promotes mandibular bicortical bone formation in a beagle dog model

Biocompatibility and osteoconductivity of porous scaffolds can be improved through coating technique by creating micro- and nanostructures on the surfaces. In this study, a biomimetic approach was used to construct a bone morphogenetic protein-2 (BMP-2) integrated calcium phosphate (CaP) coating on the surface of porous titanium scaffolds. In vitro characterizations showed that the scaffolds had mechanical properties comparable to those of the human cortical bone. The biomimetic coating has a nano-scaled surface structure, which releases BMP-2 in a stable and effective manner. Bicortical bone defects were prepared in the bilateral mandibles of beagle dogs, and the coated and uncoated scaffolds were fixed in the bone defects for 8 weeks. Based on micro-CT and histological analysis results, the biomimetic coating significantly promoted bone formation in the titanium scaffold. The coated scaffold group had significantly higher bone volume fraction, bone area fraction, and bone-to-implant contact results than the uncoated scaffold group. Besides, hematological indexes and histopathology results of the visceral organs confirmed the scaffold and coating's biocompatibility. Accordingly, the current study demonstrates that BMP-2 integrated biomimetic CaP coating can significantly promote bone formation in porous titanium scaffolds and benefit the healing process of the bicortical mandibular defect in beagle dogs.

Towards resorbable 3D-printed scaffolds for craniofacial bone regeneration.

This review will briefly examine the development of 3D-printed scaffolds for craniofacial bone regeneration. We will, in particular, highlight our work using Poly(L-lactic acid) (PLLA) and collagen-based bio-inks. This paper is a narrative review of the materials used for scaffold fabrication by 3D printing. We have also reviewed two types of scaffolds that we designed and fabricated. Poly(L-lactic acid) (PLLA) scaffolds were printed using fused deposition modelling technology. Collagen-based scaffolds were printed using a bioprinting technique. These scaffolds were tested for their physical properties and biocompatibility. Work in the emerging field of 3D-printed scaffolds for bone repair is briefly reviewed. Our work provides an example of PLLA scaffolds that were successfully 3D-printed with optimal porosity, pore size and fibre thickness. The compressive modulus was similar to, or better than, the trabecular bone of the mandible. PLLA scaffolds generated an electric potential upon cyclic/repeated loading. The crystallinity was reduced during the 3D printing. The hydrolytic degradation was relatively slow. Osteoblast-like cells did not attach to uncoated scaffolds but attached well and proliferated after coating the scaffold with fibrinogen. Collagen-based bio-ink scaffolds were also printed successfully. Osteoclast-like cells adhered, differentiated, and survived well on the scaffold. Efforts are underway to identify means to improve the structural stability of the collagen-based scaffolds, perhaps through mineralization by the polymer-induced liquid precursor process. 3D-printing technology is promising for constructing next-generation bone regeneration scaffolds. We describe our efforts to test PLLA and collagen scaffolds produced by 3D printing. The 3D-printed PLLA scaffolds showed promising properties akin to natural bone. Collagen scaffolds need further work to improve structural integrity. Ideally, such biological scaffolds will be mineralized to produce true bone biomimetics. These scaffolds warrant further investigation for bone regeneration.

Characterization of 3D printed biodegradable piezoelectric scaffolds for bone regeneration.

The primary objective of this research was to develop a poly(l-lactic acid)(PLLA) scaffold and evaluate critical characteristics essential for its biologic use as a craniofacial implant. PLLAscaffolds were designed and fabricated using fused deposition modeling technology. The surface morphology and microarchitecture were analyzed using scanning electron microscopy (SEM) and microCT, respectively. Crystallography, compressive modulus, and the piezoelectric potential generated upon mechanical distortion were characterized. Hydrolytic degradation was studied. MG63 osteoblast-like cell proliferation and morphology were assessed. The porosity of the scaffolds was 73%, with an average pore size of 450 µm and an average scaffold fiber thickness of 130 µm. The average compressive modulus was 244 MPa, and the scaffolds generated an electric potential of 25 mV upon cyclic/repeated loading. The crystallinity reduced from 27.5% to 13.9% during the 3D printing process. The hydrolytic degradation was minimal during a 12-week period. Osteoblast-like cells did not attach to the uncoated scaffold but attached well after coating the scaffold with fibrinogen. They then proliferated to cover the complete scaffold by Day 14. The PLLA scaffolds were designed and printed, proving the feasibility of 3D printing as a method of fabricating PLLA scaffolds. The elastic modulus was comparable to that of trabecular bone, and the piezoelectric properties of the PLLA were retained after 3D printing. The scaffolds were cytocompatible. These 3D-printed PLLA scaffolds showed promising properties akin to the natural bone, and they warrant further investigation for bone regeneration.

Processing of gelatine coated composite scaffolds based on magnesium and strontium doped hydroxyapatite and yttria-stabilized zirconium oxide

Limited bone bank capacity and risk of infection are some of the main drawbacks of autologous and allogenic grafts, giving rise to synthetic materials for bone tissue implants. The aim of this study was to process and evaluate the mechanical properties and bioactivity of magnesium and strontium doped hydroxyapatite (HAp) scaffolds and investigate the effect of adding zirconium oxide and gelatine coating the scaffolds. Doped nanosized hydroxyapatite powder was synthesized by the hydrothermal method and the scaffolds were made by the foam replica technique and sintered at different temperatures. Yttria-stabilized zirconium oxide (YSZ), synthesized by plasma technology, was used as reinforcement of calcium phosphate scaffolds. Element analysis, phase composition, morphology of the powders and microstructure of the scaffolds were investigated, as well as the compressive strength of the coated and uncoated scaffolds and bioactivity in simulated body fluid (SBF). A microporous structure was achieved with interconnected pores and bioactivity in SBF was confirmed in all cases. The best mechanical properties were given by the coated composite HAp/YSZ scaffolds, withstanding average stresses of over 1019 kPa. These results encourage the idea of use of these scaffolds in bone regenerative therapy and bone tissue engineering.