Printing Of Scaffolds Research Articles

3D štampa i karakterizacija nosača za dostavu ibuprofena u koštanom tkivu

In this work, a blend of gelatin A (GA) and polyvinylpyrrolidone (PVP K30) was used for semi-solid 3D printing of bone scaffold for ibuprofen (IBU) delivery. The cross-linking of the obtained scaffold was performed with a 1% glutaraldehyde (GTA) solution, followed by lyophilization. The thermal and mechanical properties, as well as drug release profiles, and drug kinetics of prepared scaffolds were investigated. The cross-linked and lyophilized scaffold has shown good thermal stability, mechanical properties, and prolonged release of IBU following the Fickian diffusion process.

The mechanical reliability of vat photopolymerization 3D printing of isosorbide-derived polyester porous tissue engineering scaffolds.

Photo-crosslinkable polymers are being studied as a potential 3D printable solution to the well-established need for biocompatible, highly elastic, and resorbable materials. Among the emerging materials that meet this need is a sugar-based polymer, an isosorbide-derived polyester, which represents a candidate for use in tissue engineered medical devices. Isosorbide polyesters are known to exhibit time-certain resorption profiles, offering not just biocompatibility and biodegradability, but can also be 3D printed by photocrosslinking. The 3D printing of medical devices requires accuracy, minimally, in the 10’s of microns range. Preliminary data showing isosorbide-derived polyester 3D printing of scaffolds with an internal porosity is reported here. The pore geometry we used is Schoen’s gyroid. Using an EnvisionTEC 3D printer (Dearborn, MI) we designed cylinders with 81% porosity using the gyroid pore geometry with a pore size of 800 µm and a strut size of 1000 µm.

Exploring Properties of Edible Hydrolyzed Collagen for 3D Food Printing of Scaffold for Biomanufacturing Cultivated Meat

Cultivated meat is being explored as one of the sustainable solutions, complementing traditional meat manufacturing to meet global demand. This paper presents the novel results of a 3D food printing process for scaffolds produced from edible hydrolyzed collagen intended for biomanufacturing cultivated meat. The hydrolyzed collagen ink is designed with combinatorial chemistries and post-printing freeze-dried to create scaffold constructs. Rheological properties of the ink for 3D food printing are studied. Variation in average pore size and pore morphology of the scaffold caused by changing collagen ink composition and freeze-drying conditions is analyzed. This novel study focuses on using commercially available food-grade ingredients for cultivated meat scaffolds. Results of this study are applied to explore the viability of edible hydrolyzed collagen scaffold biomanufacturing with appropriate pore morphology using 3D food printing and freeze-drying technique.

Novel design for an additively manufactured nozzle to produce tubular scaffolds via fused filament fabrication

Additive Manufacturing of scaffolds with controlled porosity has demonstrated its value in many fields such as tissue regeneration and filtration applications. However, there is a scarcity of reports investigating the manufacturing of scaffolds with hollow fibers. Mainly, this was due to the lack of proper tools (extrusion nozzles) that enable the production of such structures. In this study, a methodology for designing and manufacturing a nozzle that can be fitted onto a fused filament fabrication 3D printer is proposed. Titanium laser powder bed fusion technology, coupled with chemical polishing, was used to produce the complex design of the nozzle with minimal post processing steps. Through this approach, we were able to produce a nozzle with the required internal structure. Numerical simulations and experimental analyses were conducted to better understand the melt flow behavior within the nozzle and the extrudate swell. The designed nozzle was capable of extruding tubular fibers with an outer and inner diameter of 1.3 mm and 0.5 mm, respectively. This, for example, enables the fabrication of tissue regeneration scaffolds with hollow fibers. This proposed method for designing and manufacturing can be used to produce nozzles capable of 3D printing scaffolds that best suit the intended application.

Electroactive 3D printable poly(3,4-ethylenedioxythiophene)-graft-poly(ε-caprolactone) copolymers as scaffolds for muscle cell alignment

Graft copolymers between conducting PEDOT and biodegradable PCL were synthesized and investigated for 3D printing scaffolds for patterning of muscle cells.

Preparation of 3D Printing PLGA Scaffold with BMP-9 and P-15 Peptide Hydrogel and Its Application in the Treatment of Bone Defects in Rabbits.

Objective To prepare a three-dimensional (3D) printing polylactic acid glycolic acid (PLGA) scaffold with bone morphogenetic protein-9 (BMP-9) and P-15 peptide hydrogel and evaluate its application in treating bone defects in rabbits. Methods 3D printing PLGA scaffolds were formed and scanned by electron microscopy. Their X-ray diffraction (XRD), in vitro degradation, and compressive strength were characterized. BMP-9 and P-15 hydrogels were prepared. Flow cytometry was used to detect apoptosis, and an electron microscope was used to evaluate cell adhesion to scaffolds. Alkaline phosphatase (ALP), type 1 collagen (Col-I), osteocalcin (OCN), runt-related transcription factor 2 (RUNX2), and osterix (SP7) were detected by western blotting. MicroCT was used to detect new bone formation, and bone tissue-related protein expressions were determined in the rabbit model with bone defects. Results The 3D printing scaffolds were cylindrical, and the inner diameter of the scaffolds was about 1 mm. The bread peak with wide distribution showed that the 3D printing only involved a physical change, which did not change the properties of the materials. The degradation rate of scaffolds was 9.38%, which met the requirements of properties of biological scaffolds. The water absorption of the support was about 9.09%, and the compressive strength was 15.83 N/mm2. In the coculture of bone marrow mesenchymal stem cells (BMSCs) with scaffolds, the 2% polypeptide hydrogel showed the most obvious activity in promoting the differentiation of BMSCs. Flow cytometry showed that the 0% and 2% groups did not cause obvious apoptosis compared with the control group. Scaffolds with 2% and 4% polypeptide promoted the expression of ALP, COL-1, OCN, RUNX2, and Sp7 in BMSCs. In vivo experiments showed that the expression of ALP, COL-1, OCN, RUNX2, and Sp7 protein in the 2% polypeptide scaffold group increased significantly compared with the model group. MicroCT detection demonstrated that the 2% polypeptide scaffold had good bone repair ability. Conclusion The PLGA scaffolds combined with BMP-9 and P-15 peptide hydrogels had good biological and mechanical properties and could repair bone defects in rabbits.

Photopolymerized 3D Printing Scaffolds with Pt(IV) Prodrug Initiator for Postsurgical Tumor Treatment.

Biomedical scaffolds have shown great success in postsurgical tumor treatment; their current efforts are focusing on eradicating residual tumor cells and circulating tumor cells and simultaneously repairing postoperative tissue defects. Herein, we report a novel photopolymerized 3D scaffold with Pt(IV) prodrug initiator to achieve the desired features for tumor comprehensive therapy. The Pt-GelMA scaffold was fabricated from the microfluidic 3D printing of methacrylate gelatin (GelMA) bioinks through a Pt(IV)-induced photocrosslinked process without any other additional photoinitiator and chemotherapeutic drug. Thus, the resultant scaffold displayed efficient cell killing ability against breast cancer cells in vitro and significantly inhibited the local tumor growth and distant metastases on an orthotopic postoperative breast cancer model in vivo. Besides, benefiting from their ordered porous structures and favorable biocompatibility, the scaffolds supported the cell attachment, spreading, and proliferation of normal cells in vitro; could facilitate the nutrient transportation; and induced new tissue ingrowth for repairing tissue defects caused by surgery. These properties indicate that such 3D printing scaffold is a promising candidate for efficient postoperative tumor treatment in the practical application.

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.

Tricomposite gelatin-carboxymethylcellulose-alginate bioink for direct and indirect 3D printing of human knee meniscal scaffold

The development of technologies that could ease the production of customizable patient-specific tissue engineering constructs having required biomechanical properties and restoring function in damaged tissue is the need of the hour. In this study, we report the optimization of composite, bioactive and biocompatible tripolymeric hydrogel bioink, suitable for both direct and indirect printing of customizable scaffolds for cartilage tissue engineering applications. A customized hierarchical meniscal scaffold was designed using solid works software and developed using a negative mould made of polylactic acid (PLA) filament and by a direct 3D printing process. A composite tripolymeric bioink made of gelatin, carboxymethyl cellulose (CMC) and alginate was optimized and characterized for its printability, structural, bio-mechanical and bio-functional properties. The optimized composite hydrogel bioink was extruded into the negative mould with and without live cells, cross-linked and the replica of meniscus structure was retrieved aseptically. The cellular proliferation, apatite formation, and extracellular matrix secretion from negative printed meniscal scaffold were determined using MTT, live/dead and collagen estimation assays. A significant increase in collagen secretion, cellular proliferation and changes in biomechanical properties was observed in the 3D scaffolds with MG63-osteosarcoma cells indicating its suitability for cartilage tissue engineering.

Processing and properties of PLA/Mg filaments for 3D printing of scaffolds for biomedical applications

PurposeThis paper aims to develop a novel strategy to manufacture poly-lactic acid (PLA) filaments reinforced with Mg particles for fused filament fabrication of porous scaffolds for biomedical applications.Design/methodology/approachThe mixture of PLA pellets and Mg particles was extruded twice, the second time using a precision extruder that produces a filament with zero porosity, constant diameter and homogeneous dispersion of Mg particles. The physico-chemical properties of the extruded filaments were carefully analysed to determine the influence of Mg particles on the depolymerisation of PLA during high temperature extrusion and the optimum melt flow index to ensure printability.FindingsIt was found that the addition of a polyethylene glycol (PEG) plasticizer was necessary to allow printing when the weight fraction of Mg was above 4%. It was possible to print porous face-centre cubic scaffolds with good geometrical accuracy and minimum porosity with composite filaments containing PEG.Originality/valueThe new strategy is easily scalable and seems to be very promising to manufacture biodegradable thermoplastic/metal composite filaments for 3D printing that can take advantage of the different properties of both components from the viewpoint of tissue engineering.

Precision 3D printed meniscus scaffolds to facilitate hMSCs proliferation and chondrogenic differentiation for tissue regeneration

BackgroundThe poor regenerative capability and structural complexity make the reconstruction of meniscus particularly challenging in clinic. 3D printing of polymer scaffolds holds the promise of precisely constructing complex tissue architecture, however the resultant scaffolds usually lack of sufficient bioactivity to effectively generate new tissue.ResultsHerein, 3D printing-based strategy via the cryo-printing technology was employed to fabricate customized polyurethane (PU) porous scaffolds that mimic native meniscus. In order to enhance scaffold bioactivity for human mesenchymal stem cells (hMSCs) culture, scaffold surface modification through the physical absorption of collagen I and fibronectin (FN) were investigated by cell live/dead staining and cell viability assays. The results indicated that coating with fibronectin outperformed coating with collagen I in promoting multiple-aspect stem cell functions, and fibronectin favors long-term culture required for chondrogenesis on scaffolds. In situ chondrogenic differentiation of hMSCs resulted in a time-dependent upregulation of SOX9 and extracellular matrix (ECM) assessed by qRT-PCR analysis, and enhanced deposition of collagen II and aggrecan confirmed by immunostaining and western blot analysis. Gene expression data also revealed 3D porous scaffolds coupled with surface functionalization greatly facilitated chondrogenesis of hMSCs. In addition, the subcutaneous implantation of 3D porous PU scaffolds on SD rats did not induce local inflammation and integrated well with surrounding tissues, suggesting good in vivo biocompatibility.ConclusionsOverall, this study presents an approach to fabricate biocompatible meniscus constructs that not only recapitulate the architecture and mechanical property of native meniscus, but also have desired bioactivity for hMSCs culture and cartilage regeneration. The generated 3D meniscus-mimicking scaffolds incorporated with hMSCs offer great promise in tissue engineering strategies for meniscus regeneration.Graphical

Projection printing of scaffolds with shape recovery capacity and simultaneously improved stiffness and toughness using an ultra-fast-curing poly(propylene fumarate)/hyperbranched additive resin

Projection micro-stereolithography (PμSL) is an effective technique to rapidly fabricate porous scaffolds with complex structures of photo-crosslinkable polymer resins, which normally contain a reactive diluent and a photo-initiator. In previous reports on 3D printing of poly(propylene fumarate) (PPF) scaffolds, diethyl fumarate (DEF) was unavoidably used as a reactive diluent in the PPF resin. Here we present a photo-crosslinkable resin composed of PPF and hyperbranched polyester acrylate (HPA), which has multiple carbon-carbon double bonds to participate in photo-crosslinking as a reactive diluent, and PμSL 3D fabrication of tissue-engineering scaffolds using this resin. The structure and viscoelastic behavior of uncrosslinked PPF/HPA, and the gel fraction, thermal and mechanical properties of photo-crosslinked PPF/HPA samples have been investigated, in comparison with those of PPF/DEF. Blending HPA with PPF was found to decrease the viscosity of PPF and to expedite the photo-crosslinking process, both of which are important in formation of PPF networks. In addition, HPA can effectively enhance the stiffness and toughness of the fabricated network simultaneously. In PμSL 3D fabrication, the cure depth (C d ) experiments proved that the PPF/HPA resin had an extremely low critical energy (E c ) of 2.1 mJ/cm 2 , leading to ultra-fast curing when exposed to ultraviolet (UV) light. Our rapid prototyping characteristics are evident under the premise of ensuring high precision. For the PPF/HPA resin, the exposure time per layer was only 0.1–2 s, which at least doubled the printing speed compared with the other 3D fabrication techniques. At high printing resolution of 50 µm, an ultra-fast printing speed of 18 cm/h was achieved by using the PPF/HPA resin, while the value for the PPF/DEF resin was only 3.6 cm/h. Benefited from the better crosslinked networks, the fabricated PPF/HPA scaffolds exhibited a lower shrinkage, higher stiffness and toughness, and better recovery capacity than their PPF/DEF counterparts, indicating their 4D printing characteristics.

Fabrication and characterization of 3D printing scaffold technology by extract oils from plant and its applications in the cardiovascular blood

Extract oils from plants used in 3D polysaccharides modified with natural protein polymer modified polymer scaffolds can help to reduce blood pressure. This study aimed to use extract oils from plant (EOP)as blood pressure-reducing, bind them to magnetic iron nanoparticles (Fe3O4@NPs), then bind them to polymeric 3D print scaffolds [chitosan, polylactic acid, and polyurethane (CS/PLA/PU), modified with natural protein and finally separate them. This method made it possible to investigate different variables for nanoparticles. In this project, synthesis polymer, modified gelatin (Mo-Ge), PEGylation, extract oils from plant loading and release process in nanocarrier with different concentrations were examined and cell proliferation was optimized. The results show that 75% of the extract oils from plant loaded on iron magnetic nanoparticles containing PEGylated polymer scaffolds was released. Cell proliferation was performed for the sample. In this process, modification of scaffolding with polysaccharides modified with natural protein and extract oils from plant increased the efficiency of nanoparticles among the studied Allium sativum and Zingiber officinale. The size of A. sativum and Z. officinale were 29.833 nm and 150.02 nm size, respectively. These behaved very similarly to each other and A. sativum had the biggest effect in lowering blood pressure. The application of extract oils from plant in 3D mode scaffolding has not been studied before and this is the first analysis to do so, using nanoparticles.

3D Printed In Vitro Dentin Model to Investigate Occlusive Agents against Tooth Sensitivity.

Tooth sensitivity is a painful and very common problem. Often stimulated by consuming hot, cold, sweet, or acidic foods, it is associated with exposed dentin microtubules that are open to dental pulp. One common treatment for tooth hypersensitivity is the application of occlusive particles to block dentin microtubules. The primary methodology currently used to test the penetration and occlusion of particles into dentin pores relies upon dentin discs cut from extracted bovine/human teeth. However, this method is limited due to low accessibility to the raw material. Thus, there is a need for an in vitro dentin model to characterize the effectiveness of occlusive agents. Three-dimensional printing technologies have emerged that make the printing of dentin-like structures possible. This study sought to develop and print a biomaterial ink that mimicked the natural composition and structure of dentin tubules. A formulation of type I collagen (Col), nanocrystalline hydroxyapatite (HAp), and alginate (Alg) was found to be suitable for the 3D printing of scaffolds. The performance of the 3D printed dentin model was compared to the natural dentin disk by image analysis via scanning electron microscopy (SEM), both pre- and post-treatment with occlusive microparticles, to evaluate the degree of dentinal tubule occlusion. The cytocompatibility of printed scaffolds was also confirmed in vitro. This is a promising biomaterial system for the 3D printing of dentin mimics.

Processing and properties of PLA/Mg filaments for 3D printing of scaffolds for biomedical applications

Processing and properties of PLA/Mg filaments for 3D printing of scaffolds for biomedical applications

3D printing of a titanium-tantalum Gyroid scaffold with superb elastic admissible strain, bioactivity and in-situ bone regeneration capability

The simultaneous achievement of admirable mechanical compatibility and osteoinduction in metallic implants can avoid stress shielding and facilitate osseointegration and osteogenesis. Herein, we reported a titanium-tantalum (Ti-Ta) Gyroid scaffold in-situ fabricated with selective laser melting (SLM), a powder-bed-fusion three-dimensional (3D) printing process, enabling superb elastic admissible strain (EAS), bioactivity and in-situ bone regeneration capability. The printed scaffold with 90% porosity exhibited a good combination of low elastic modulus (1.8 GPa) and high compressive yield strength (55.5 MPa), resulting in a superb EAS (3.03%) that is suitable for the reconstruction of cancellous bone. The mechanisms of the high EAS were ascribed to the formation of β(Ti, Ta) solid solution, ultrafine β grains accompanying with nanocrystalline α' grains, and the existence of dislocations and stacking faults. Bone-like apatite was spontaneously induced on the surface of the printed Ti-Ta alloy due to the generation of self-passivating Ta2O5 film, indicating a good biomineralization ability. Compared to pure Ti, the printed Ti-Ta alloy exhibited enhanced expression of vinculin, earlier cell extension, increased nuclei density, better cell proliferation, and the up-regulated expression of osteogenesis genes. Animal studies further validated that the printed Ti-Ta scaffold was capable to reinforce bone integration and accelerate bone regeneration. These findings provided a promising strategy for treating bone defects through 3D printing of metallic scaffolds.

The Challenge of 3D Bioprinting of Composite Natural Polymers PLA/Bioglass: Trends and Benefits in Cleft Palate Surgery.

Cleft lip and palate is the fourth most common congenital malformation. Its prevalence is about 1 in 750 to 1 in 2000 live births. The consequences of this malformation are major: maxillary growth deficit, unaesthetic appearance, phonation disorders, difficulty in eating, and psycho-social disorders. Cleft palate repair establishes the division between the oral and nasal cavities. The alveolar bone graft is a key step. Different sites of autogenous bone harvesting are used, the most common being the iliac crest. Nevertheless, the large number of complications associated with harvesting has led to the use of substitute biomaterials. Bioactive glasses, discovered in 1969, are a group of synthetic silica-based materials with bone-bonding properties. Although 45S5 granular composition is commonly used in bone surgery to repair critical defects, it is only rarely used in the repair of cleft palates because this galenic form is only moderately adapted. However, advances in bone tissue engineering allow the shaping of three-dimensional scaffolds, which support colonization by host cells. Recent advances in computer-aided design/computer-aided manufacturing (CAD/CAM) have even led to the 3D printing of scaffolds combining 45S5 bioglass with a natural and biocompatible poly-lactic acid matrix. The shape of the parts is customized and adapted to the particular shape of the critical bone defects. The objective of this literature review is to highlight the particularities of alveolar defects subsequent to facial clefts, then to detail the characteristics of the materials and technologies used to elaborate 3D matrices by bioprinting. Finally, we will explore research directions regarding their use in reconstructive surgery of cleft palates.

3D Printing Scaffold Vaccine for Antitumor Immunity.

Cancer vaccine platform has attracted great interest in the field of cancer immunotherapy. Here, 3D printed scaffolds loaded with immunoregulators are developed for enhanced cancer immunotherapy. The rapid manufacturing and precise molding based on 3D printing can realize the mass manufacturing of cancer vaccines and personalized design. Meanwhile, compared to the traditional hydrogel, the 3D-scaffold with porous structure endows its similar functions compared with real lymphoid organs by recruitment of a great number of immune cells, leading to the formation of "artificial tertiary lymphoid structures," where there is a promising site to enhance both humoral and cellular immune responses. Efficient anticancer immunity is induced when combined with immune checkpoint blockade to inhibit the tumor growth. Personalized antitumor scaffold vaccines are further demonstrated for filling of tumor site after surgery to prevent cancer metastasis. Taken together, these results promise the 3D printing scaffold vaccine as the potential strategy for cancer vaccine therapy in the future.

1286 3D Printing of Aortic Valve Scaffolds for Heart Valve Regeneration

Abstract Introduction Valvular heart disease (VHD) has been commonly described as the forgotten epidemic, with an estimated global prevalence of 2.5%. Current heart valve replacement therapies only partially offer a solution to the problem. In recent years, synthetic polymers have been explored due to their diversity allowing tailor-picking of essential traits, such as chemical properties, physical properties, and degradation states. This project investigated the feasibility and mechanical properties of reverse three-dimensional printing of biodegradable scaffolds for heart valve regeneration. Method Aortic valve dimensions at an average of 100mmHg were used for the computer aided design of the valves. Aortic valve scaffolds were fabricated using the 3D-TIPs reverse printing technique. Infill densities of 30%, 40% or 50% were used. Printed polymer scaffolds were coated in gelatine solution and compared using static tensile tests. Static strength and elasticity of coated and uncoated valves were compared. Results At 25%, 50% and 100% strain, significantly different elastic properties in favour of coated scaffolds between coated and uncoated valves was observed. Coated valves displayed greater strength than uncoated valves (p > 0.05). Computer aided design (CAD) software designed anatomically accurate scaffolds, but poor polymer coagulation was observed on the valve cusps. Conclusions The reverse-printing 3D-TIPS procedure successfully produces heart valve scaffolds which present architectural similarities to the naïve mitral valve, however, dimensions of the valves ought to be reassessed. Gelatine-coated valves exhibit greater elastic and tensile properties. A further understanding of cellular interactions on the polymer scaffold, in particular in vivo studies, are required for the continuity of future study.

Open-source CAD-CAM simulator of the extrusion-based bioprinting process

Extrusion-based Bioprinting (EBB) represents one of the most used Bioprinting technologies among researchers, thanks to its ease of use, wide variety of available materials, and affordable cost. Even though the technique has successfully been applied in bioprinting constructs for Tissue Engineering applications, there is still no consensus on which parameters have more influence of the accuracy of bioprinted scaffolds. Moreover, the literature lacks a rapid and robust method to consistently set the printing parameters before the actual printing phase, thus minimizing the trial-and-error process. In this context, we present a mathematical model for understanding the printability of a defined structure by depositing a given biomaterial ink through a specific EBB apparatus. The model takes into account different steps of the printing process, including extrusion, line formation and scaffold stabilization over time. The model was experimentally validated and implemented in an open-source software to guide the user in setting the correct printing parameters (i.e., printing speed, layer height and flow) based on scaffold dimensions, material properties (including rheological and mechanical ones) and printer set-up. To encourage the model use, we also propose a set of experiments to extract the relevant material properties for our model, and the software is available both as a stand-alone program (available at https://github.com/CentroEPiaggio/Rheology-GUI), as well as a webpage (available at https://www.prin-vision.it/printability-assessment).