Artificial Scaffolds Research Articles

Biofunctionalization of electrospun fiber membranes by LbL-collagen/chondroitin sulfate nanocoating followed by mineralization for bone regeneration

It is of great significance to develop osteoinductive artificial scaffold for bone repair and regeneration. We constructed a biomimetic apatite interface on electrospun polycaprolactone fibers by combining layer-by-layer (LbL) nanocoating with mineralization to fabricate an osteoinductive artificial scaffold. After polydopamine modification, cationic type-І collagen and anionic chondroitin sulfate were sequentially adsorbed on the fiber surface. The fibers coated with the multilayer components served as the precursor matrix to induce apatite deposition. By adjusting the number of the layers and duration of mineralization, the nanoscale morphology of composite fibers was optimized. When ten bilayers of the collagen and chondroitin sulfate were deposited onto the fibers followed by one day-mineralization, the obtained polycaprolactone–apatite composite scaffolds significantly promoted the adhesion, proliferation, and osteogenic differentiation of MC3T3-E1 cells. In a subcutaneous implantation in mice, this composite fiber membrane enhanced in vivo ectopic osteogenesis. Our nano-architectural scaffolds were able to mimic the composition and structure of the bone matrix to a certain extent, holding great potential for bone repair and regeneration.

Nano-Hydroxyapatite Scaffold Based on Recombinant Human Bone Morphogenetic Protein 2 and Its Application in Bone Defect Repair.

The best way in which to prepare scaffolds with good biological properties is an urgent problem in the field of tissue engineering. In this paper we discuss the preparation of nano-hydroxyapatite scaffold of recombinant human bone morphogenetic protein-2 (rhBMP-2) and its application in bone defect repair. rhBMP-2 reagent was dissolved in 1 mol/L sodium dihydrogen phosphate solution, and the rhBMP-2 solution was added to the nano-hydroxyapatite artificial bone with a 100 μL glass micro dropper at the rate of 10 drops/min to obtain Nano-HA/rhBMP-2 composite artificial bone. In in vivo experiments, rabbits were fixed on an operating table, a 2 cm longitudinal incision was made in the middle part of the radial forearm, and the radius was cut with a wire saw and periosteum, 2.5 cm away from the distal radius. After washing the wound with normal saline, Adv-hBMP-2/MC3T3-E1 nano-HA composite artificial bone, MC3T3-E1 nan-HA composite artificial bone, or Nano-HA artificial bone were implanted in different groups. The artificial bone scaffold prepared in this study has a stronger ability to repair bone defects than the alternatives, and is a promising prospect for the clinical treatment of bone defects.

PLGA Nanoparticles Decorated with Anti-HER2 Affibody for Targeted Delivery and Photoinduced Cell Death.

The effect of enhanced permeability and retention is often not sufficient for highly effective cancer therapy with nanoparticles, and the development of active targeted drug delivery systems based on nanoparticles is probably the main direction of modern cancer medicine. To meet the challenge, we developed polymer PLGA nanoparticles loaded with fluorescent photosensitive xanthene dye, Rose Bengal, and decorated with HER2-recognizing artificial scaffold protein, affibody ZHER2:342. The obtained 170 nm PLGA nanoparticles possess both fluorescent and photosensitive properties. Namely, under irradiation with the green light of 540 nm nanoparticles, they produced reactive oxygen species leading to cancer cell death. The chemical conjugation of PLGA with anti-HER2 affibody resulted in the selective binding of nanoparticles only to HER2-overexpressing cancer cells. HER2 is a receptor tyrosine kinase that belongs to the EGFR/ERbB family and is overexpressed in 30% of breast cancers, thus serving as a clinically relevant oncomarker. However, the standard targeting molecules such as full-size antibodies possess serious drawbacks, such as high immunogenicity and the need for mammalian cell production. We believe that the developed affibody-decorated targeted photosensitive PLGA nanoparticles will provide new solutions for ongoing problems in cancer diagnostics and treatment, as well in cancer theranostics.

Polybutylene succinate artificial scaffold for peripheral nerve regeneration.

Regeneration and recovery of nerve tissues are a great challenge for medicine, and positively affect the quality of life of patients. The development of tissue engineering offers a new approach to the problem with the creation of multifunctional artificial scaffolds that act on various levels in the damaged tissue, providing physical and biochemical support for the growth of nerve cells. In this study, the effects of the use of a tubular scaffold made of polybutylene succinate (PBS), surgically positioned at the level of a sciatic nerve injured in rat, between the proximal stump and the distal one, was investigated. Scaffolds characterization was carried out by scanning electron microscopy and X‐ray microcomputed tomography and magnetic resonance imaging, in vivo. The demonstration of the nerve regeneration was based on the evaluation of electroneurography, measuring the weight of gastrocnemius and tibialis anterior muscles, histological examination of regenerated nerves and observing the recovery of the locomotor activity of animals. The PBS tubular scaffold minimized iatrogenic trauma on the nerve, acting as a directional guide for the regenerating fibers by conveying them toward the distal stump. In this context, neurotrophic and neurotropic factors may accumulate and perform their functions, while invasion by macrophages and scar tissue is hampered.

Comparative Evaluation of Engineered Polypeptide Scaffolds in HER2-Targeting Magnetic Nanocarrier Delivery.

Targeted drug delivery is one of the most intriguing and challenging issues in modern biomedicine. For active targeting, full-size IgG molecules (150 kDa) are usually used. Recent studies have revealed that small artificial polypeptide scaffolds such as DARPins (14 kDa) and affibodies (8 kDa) are much more promising tools for drug delivery due to their small size, artificial nature, low immunogenicity, and many other properties. However, there is no comparative information on the targeting abilities of scaffold polypeptides, which should be taken into account when developing drug delivery systems (DDSs). The present work is the first comprehensive study on the comparison of the effectiveness of different HER2-targeting proteins within the architecture of nanoparticles. Namely, we synthesized trimodal nanoparticles: magnetic, fluorescent, and directed toward HER2 oncomarker on cancer cells. The magnetic particles (MPs) were covalently modified with (i) full-size IgG, 150 kDa, (ii) DARPin_G3, 14 kDa, and (iii) affibody ZHER2:342, 8 kDa. We showed that the number of DARPin_G3 and affibody ZHER2:342 molecules conjugated to the nanoparticle surface are 10 and 40 times higher, respectively, than the corresponding value for trastuzumab. Using the methods of magnetic particle quantification (MPQ)-cytometry and confocal microscopy, we showed that all types of the obtained magnetic conjugates specifically labeled HER2-overexpressing cells. Namely, we demonstrated that particle binding to HER2-positive cells is 1113 ± 39 fg/cell for MP*trastuzumab, 1431 ± 186 fg/cell for MP*ZHER2:342, and 625±21 fg/cell for MP*DARPin_G3, which are 2.77, 2.75, and 2.30 times higher than the corresponding values for control HER2-negative cells. Thus, we showed that the smallest HER2-recognizing polypeptide affibody ZHER2:342 is more effective in terms of specificity and selectivity in nanoparticle-mediated cell labeling.

Heterotypic Tumor Spheroids in Agitation-Based Cultures: A Scaffold-Free Cell Model That Sustains Long-Term Survival of Endothelial Cells.

Endothelial cells (ECs) are an important component of the tumor microenvironment, playing key roles in tumor development and progression that span from angiogenesis to immune regulation and drug resistance. Heterotypic tumor spheroids are one of the most widely used in vitro tumor microenvironment models, presenting improved recapitulation of tumor microenvironments compared to 2D cultures, in a simple and low-cost setup. Heterotypic tumor spheroid models incorporating endothelial cells have been proposed but present multiple limitations, such as the short culture duration typically obtained, the use of animal-derived matrices, and poor reproducibility; the diversity of culture conditions employed hinders comparison between studies and standardization of relevant culture parameters. Herein, we developed long-term cultures of triple heterotypic spheroids composed of the HCC1954 tumor cell line, human fibroblasts, and ECs. We explored culture parameters potentially relevant for EC maintenance, such as tumor cell line, seeding cell number, cell ratio, and agitation vs. static culture. In HCC1954-based spheroids, we observed maintenance of viable EC for up to 1 month of culture in agitation, with retention of the identity markers CD31 and von Willebrand factor. At the optimized tumor cell:fibroblast:EC ratio of 1:3:10, HCC1954-based spheroids had a higher EC area/total spheroid area at 1 month of culture than the other cell ratios tested. EC maintenance was tumor cell line-dependent, and in HCC1954-based spheroids it was also dependent on the presence of fibroblasts and agitation. Moreover, vascular endothelial growth factor (VEGF) supplementation was not required for maintenance of EC, as the factor was endogenously produced. ECs co-localized with fibroblasts, which accumulated preferentially in the core of the spheroids and secreted EC-relevant extracellular matrix proteins, such as collagen I and IV. This simple model setup does not rely on artificial or animal-derived scaffolds and can serve as a useful tool to explore the culture parameters influencing heterotypic spheroids, contributing to model standardization, as well as to explore molecular cross talk of ECs within the tumor microenvironment, and potentially its effects on drug response.

Design and Hybridization Properties of Acyclic Xeno Nucleic Acid Oligomers.

Xeno nucleic acids (XNAs) are analogues of DNA and RNA that have a non-ribose artificial scaffold. XNAs are possible prebiotic genetic carriers as well as alternative genetic systems in artificial life. In addition, XNA oligomers can be used as biological tools. Acyclic XNAs, which do not have cyclic scaffolds, are attractive due to facile their synthesis and remarkably high nuclease resistance. To maximize the performance of XNAs, a negatively charged backbone is preferable to provide sufficient water solubility; however, acyclic XNAs containing polyanionic backbones suffer from high entropy cost upon duplex formation, because of the high flexibility of the acyclic nature. Herein, we review the relationships between the structure and duplex hybridization properties of various acyclic XNA oligomers with polyanion backbones.

Scalable 18650 Cylindrical Cells of Lithium Metal Batteries Using Ni-Rich Cathode with Electrolyte Engineering

Li-ion batteries are approaching their theoretical limits in energy densities, motivating the revival of Li metal chemistry. Nevertheless, uncontrollable side reaction forms a chemically unstable SEI and non-uniform Li diffusion through the surface of Li anode, leading to dendritic growth. These instability and safety issues have been the main challenges of lithium metal batteries. To overcome these drawbacks, tremendous efforts have been devoted to the use of artificial solid electrolyte interphase (ASEI) engineering, lithium hosts & scaffolding, and electrolyte additives. However, the electrolyte engineering in 18650 cylindrical lithium metal cells under the practical condition, for instance, the utilization of high cathode loading (>3.5 mAh/cm2), thin lithium metal (e.g., <50 um), and lean electrolyte (<3 g/Ah)) has not been investigated yet. Herein, the first-scalable 18650 lithium metal battery in high Ni content (>88%) NCA cathode with state-of-the-art electrolytes including fluorinated solvent, and flame-retardant additives were studied. The effect of electrolytes at the positive electrode on the active mass loss and lattice volume changes, charge transfer resistance growth, SEI/CEI composition, and lithium dendrite morphology has also been investigated by the post-mortem analysis. To achieve fundamental understanding, reactive molecular dynamic simulation (Reaxff) has been used to investigate the mechanism and compositions of the passivation layer compounds at the lithium anode. The predicted compounds have a correlation to experimental results and the cell performances in terms of capacity retention and coulombic efficiency. Figure 1

Osteogenesis of 3D-Printed PCL/TCP/bdECM Scaffold Using Adipose-Derived Stem Cells Aggregates; An Experimental Study in the Canine Mandible.

Three-dimensional (3D) printing is perceived as an innovative tool for change in tissue engineering and regenerative medicine based on research outcomes on the development of artificial organs and tissues. With advances in such technology, research is underway into 3D-printed artificial scaffolds for tissue recovery and regeneration. In this study, we fabricated artificial scaffolds by coating bone demineralized and decellularized extracellular matrix (bdECM) onto existing 3D-printed polycaprolactone/tricalcium phosphate (PCL/TCP) to enhance osteoconductivity and osteoinductivity. After injecting adipose-derived stem cells (ADSCs) in an aggregate form found to be effective in previous studies, we examined the effects of the scaffold on ossification during mandibular reconstruction in beagle dogs. Ten beagles were divided into two groups: group A (PCL/TCP/bdECM + ADSC injection; n = 5) and group B (PCL/TCP/bdECM; n = 5). The results were analyzed four and eight weeks after intervention. Computed tomography (CT) findings showed that group A had more diffuse osteoblast tissue than group B. Evidence of infection or immune rejection was not detected following histological examination. Goldner trichrome (G/T) staining revealed rich ossification in scaffold pores. ColI, Osteocalcin, and Runx2 gene expressions were determined using real-time polymerase chain reaction. Group A showed greater expression of these genes. Through Western blotting, group A showed a greater expression of genes that encode ColI, Osteocalcin, and Runx2 proteins. In conclusion, intervention group A, in which the beagles received the additional ADSC injection together with the 3D-printed PCL/TCP coated with bdECM, showed improved mandibular ossification in and around the pores of the scaffold.

Functionally assembled metal platform as lego-like module system for enhanced mechanical tunability and biomolecules delivery

Natural bone substituting materials derived from living organisms have been utilized to treat bone malfunctioning. However, limited sources and immune issues have led to the use of artificial scaffolds consisting of biocompatible materials. Additionally, a functionally graded porous structure has been acknowledged as an alternative to overcome reduced mechanical properties by pores and alleviate stress shielding effect. In this study, a two-body combination achieved through a densification process, in which recombinant human bone morphogenetic protein-2 (rhBMP-2) and tetracycline hydrochloride (TCH) can be simultaneously released for efficient bone regeneration, is proposed. Biomimetic titanium scaffolds (BTSs), which possess significantly different pore characteristics, are successfully fabricated. The mechanical properties of these parts are proven to be applicable as bone substitutes. The release of rhBMP-2 and TCH from the BTSs is prolonged compared to that of homogenous porous titanium scaffolds (PTSs). The prolonged release of rhBMP-2 from the BTS results in a sustained degree of pre-osteoblast differentiation. The antimicrobial properties of these scaffolds are verified using pathogens. Furthermore, various structures exhibiting different pore characteristics are obtained by mechanical interlocking between components. This study demonstrates that the novel assembled platform as customizable Lego-like building blocks, with its tunable mechanical and multi-biomolecule release properties, is promising for bone tissue engineering.

Magnetic Field Alignment, a Perspective in the Engineering of Collagen-Silica Composite Biomaterials.

Major progress in the field of regenerative medicine is expected from the design of artificial scaffolds that mimic both the structural and functional properties of the ECM. The bionanocomposites approach is particularly well fitted to meet this challenge as it can combine ECM-based matrices and colloidal carriers of biological cues that regulate cell behavior. Here we have prepared bionanocomposites under high magnetic field from tilapia fish scale collagen and multifunctional silica nanoparticles (SiNPs). We show that scaffolding cues (collagen), multiple display of signaling peptides (SiNPs) and control over the global structuration (magnetic field) can be combined into a unique bionanocomposite for the engineering of biomaterials with improved cell performances.

Artificial Intelligence and Cheminformatics-Guided Modern Privileged Scaffold Research.

With the rapid development of computer science in scopes of theory, software, and hardware, artificial intelligence (mainly in form of machine learning and more complex deep learning) combined with advanced cheminformatics is playing an increasingly important role in drug discovery process. This development has also facilitated privileged scaffold-related research. By definition, a privileged scaffold is a structure that frequently occurs in diverse bioactive molecules, either has a diverse family affinity or is selective to multiple family members in a superfamily, whilst it is different from the"frequent hitters", or the "pan-assay interference compounds". The long history of the use of this concept has witnessed a functional shift from stand-alone technology towards an integrated component in the drug discovery toolbox. Meanwhile, continuous efforts have been dedicated to deepening the understandings of the features of known privileged scaffolds. In this contribution, we focus on the current privileged scaffold-related research driven by state-of-art artificial intelligence approaches and cheminformatics. Representative cases with an emphasis on distinct research aspects are presented, including an update of the knowledge on privileged scaffolds, proofof- concept tools, and workflows to identify privileged scaffolds and to carry on de novo design, informatic SAR models with diversely complex data sets to provide an instructive prediction on new potential molecules bearing privileged scaffolds.

Fabrication of a dual-layer cell-laden tubular scaffold for nerve regeneration and bile duct reconstruction

Tubular scaffolds serve as a controllable extracellular environment to guide the repair and regeneration of tissues. But it is still a challenge to achieve both excellent mechanical properties and cell compatibility of artificial scaffolds for long-term structural and biological stability. In this study, a four-step solution casting method was developed to fabricate dual-layer cell-laden tubular scaffolds for nerve and bile duct regeneration. The dual-layer tubular scaffold consisted of a bone marrow mesenchymal stem cells (BMSCs)-laden hydrogel inner layer and an outer layer of gelatin methacrylate (GelMA)/polyethylene glycol diacrylate. While the inner layer had a good biocompatibility, the outer layer had desired mechanical properties. The interfacial toughness, Young’s modulus, maximum tensile strain, and compressive modulus of dual-layer tubular scaffolds were 65 J m−2, 122.37 ± 23.21 kPa, 100.87 ± 40.10%, and 39.14 ± 18.56 N m−1, respectively. More importantly, the fabrication procedure was very cell-friendly, since the BMSC viability encapsulated in the inner layer of 10% (w/v) GelMA reached 94.68 ± 0.43% after 5 d of culture. Then, a preliminary evaluation of the potential application of dual-layer tubular scaffolds as nerve conduits and biliary scaffolds was performed, and demonstrated that the cell-laden dual-layer tubular scaffolds proposed in this work are expected to extend the application of tubular scaffolds in tissue engineering.

Ca2+-supplying black phosphorus-based scaffolds fabricated with microfluidic technology for osteogenesis

Effective osteogenesis remains a challenge in the treatment of bone defects. The emergence of artificial bone scaffolds provides an attractive solution. In this work, a new biomineralization strategy is proposed to facilitate osteogenesis through sustaining supply of nutrients including phosphorus (P), calcium (Ca), and silicon (Si). We developed black phosphorus (BP)-based, three-dimensional nanocomposite fibrous scaffolds via microfluidic technology to provide a wealth of essential ions for bone defect treatment. The fibrous scaffolds were fabricated from 3D poly (l-lactic acid) (PLLA) nanofibers (3D NFs), BP nanosheets, and hydroxyapatite (HA)-porous SiO2 nanoparticles. The 3D BP@HA NFs possess three advantages: i) stably connected pores allow the easy entrance of bone marrow-derived mesenchymal stem cells (BMSCs) into the interior of the 3D fibrous scaffolds for bone repair and osteogenesis; ii) plentiful nutrients in the NFs strongly improve osteogenic differentiation in the bone repair area; iii) the photothermal effect of fibrous scaffolds promotes the release of elements necessary for bone formation, thus achieving accelerated osteogenesis. Both in vitro and in vivo results demonstrated that the 3D BP@HA NFs, with the assistance of NIR laser, exhibited good performance in promoting bone regeneration. Furthermore, microfluidic technology makes it possible to obtain high-quality 3D BP@HA NFs with low costs, rapid processing, high throughput and mass production, greatly improving the prospects for clinical application. This is also the first BP-based bone scaffold platform that can self-supply Ca2+, which may be the blessedness for older patients with bone defects or patients with damaged bones as a result of calcium loss.

Mathematical approach to design 3D scaffolds for the 3D printable bone implant

This work demonstrates that an artificial scaffold structure can be designed to exhibit mechanical properties close to the ones of real bone tissue, thus highly reducing the stress-shielding phenomenon. In this study the scan of lumbar vertebra fragment was reproduced to create a numerical 3D model (this model was called the reference bone sample). New nine 3D scaffold samples were designed and their numerical models were created. Using the finite element analysis, a static compression test was performed to assess the effective Young modulus of each tested sample. Also, two important metrics of each sample were assessed: relative density and surface area. Each new designed 3D scaffold sample was analyzed by considering two types of material properties: metal alloy properties (Ti-6Al-4V) and ABS polymer properties. Numerical analysis results of this study confirm that 3D scaffold used to design a periodic structure, either based on interconnected beams (A, B, C, D, E and F units) or made by removing regular shapes from base solid cubes (G, H, I units), can be refined to obtain mechanical properties similar to the ones of trabecular bone tissue. Experimental validation was performed on seven scaffolds (A, B, C, D, E, F and H units) printed from ABS material without any support materials by using Fused Deposition Modeling (FMD) technology. Results of experimental Young modulus of each printed scaffold are also presented and discussed.

3D-Printed Objects for Multipurpose Applications.

3D printing is a popular nonconventional manufacturing technique used to print 3D objects by using conventional and nonconventional materials. The application and uses of 3D printing are rapidly increasing in each dimension of the engineering and medical sectors. This article overviews the multipurpose applications of 3D printing based on current research. In the beginning, various popular methods including fused deposition method, stereolithography 3D printing method, powder bed fusion method, digital light processing method, and metal transfer dynamic method used in 3D printing are discussed. Popular materials utilized randomly in printing techniques such as hydrogel, ABS, steel, silver, and epoxy are overviewed. Engineering applications under the current development of the printing technique which include electrode, 4D printing technique, twisting object, photosensitive polymer, and engines are focused. Printing of medical equipment including artificial tissues, scaffolds, bioprinted model, prostheses, surgical instruments, COVID-19, skull, and heart is of major focus. Characterization techniques of the printed 3D products are mentioned. In addition, potential challenges and future prospects are evaluated based on the current scenario. This review article will work as a masterpiece for the researchers interested to work in this field.

Проводящие нановолоконные скаффолды для тканевой инженерии

One of very demanded and actively developed areas of modern biomedicine is tissue engineering, investigating synthesis and reparation of various kinds of tissues, including trauma treatment. Normally cells in tissue grow in the microenvironment provided by exttacellular matrix – a three-dimensional network of macromolecules, mostly peptides and proteins, that provide structural and biochemical support. To substitute this matrix in medical applications and promote new cells growth and repair damaged tissue, various types of artificial scaffolds are proposed. Morphology, as well as physical and chemical properties of scaffolds influence the fate of cells, including attachment, proliferation and differentiation, and strongly correlate with the type of target tissue. This review is aimed to provide a short insight in materials and technologies for synthesis of tissue engineering scaffolds, with focus on polymeric electrospun nonwoven materials and ones with conductive structures that can be potentially used to direct electrical signals to cells for the aims of electrostimulation, which was demonstrated to induce functional repairmen of certain cell types such as myocytes and neurons.

Liquid Crystal Elastomers for Biological Applications

The term liquid crystal elastomer (LCE) describes a class of materials that combine the elastic entropy behaviour associated with conventional elastomers with the stimuli responsive properties of anisotropic liquid crystals. LCEs consequently exhibit attributes of both elastomers and liquid crystals, but additionally have unique properties not found in either. Recent developments in LCE synthesis, as well as the understanding of the behaviour of liquid crystal elastomers—namely their mechanical, optical and responsive properties—is of significant relevance to biology and biomedicine. LCEs are abundant in nature, highlighting the potential use of LCEs in biomimetics. Their exceptional tensile properties and biocompatibility have led to research exploring their applications in artificial tissue, biological sensors and cell scaffolds by exploiting their actuation and shock absorption properties. There has also been significant recent interest in using LCEs as a model for morphogenesis. This review provides an overview of some aspects of LCEs which are of relevance in different branches of biology and biomedicine, as well as discussing how recent LCE advances could impact future applications.

3D printed, mechanically tunable, composite sodium alginate, gelatin and Gum Arabic (SA-GEL-GA) scaffolds

Biomimicking the mechanical properties of native tissues is one of the key requirements of engineering tissue scaffolds, rendering a need for materials and manufacturing processes with a high level of control over the mechanical properties of such scaffolds. To address this need, we present a 3D printable, composite hydrogel consisting of sodium alginate (SA), gelatin (GEL) and gum Arabic (GA), referred to herein as SA-GEL-GA hydrogel, mechanical properties of which can be controlled through tuning its cross-linking process. Here, the aqueous solution of the three constituents is used as the bioink to 3D print porous scaffolds in a temperature-controlled extrusion-based printing process. 3D-printed scaffolds are then crosslinked through a multi-step approach, realizing the gelation of GEL, ionic crosslinking of SA and GA, and covalent cross-linking of all three components. Here, we show that the inherent mechanical properties of SA-GEL-GA hydrogels can be controlled through the duration of the covalent crosslinking step. SA-GEL-GA bioinks exhibit highly temperature-dependent rheology with elastic solid-like behavior below room temperature and a viscoplastic, shear thinning nature above 28 ​°C. Using a cooled build-plate and heated printhead, high resolution scaffolds were printed with filament diameter of 250 ​μm and extruded from a 100 ​μm diameter nozzle. The compressive elastic modulus of these scaffolds can be tuned to the 50–250 ​kPa range through the combined effect of the scaffold pores size and covalent crosslinking step duration. 3D printed and crosslinked scaffolds carry over 500% of their dry weight in water and can be dried and reswollen to over 400% of their dry weight. Finally, our degradation analysis showed that increased covalent cross-linking duration led to reduced long-term structural stability due to mechanical failure of the scaffolds. These results indicate that SA-GEL-GA hydrogels offer exciting opportunities for manufacturing customizable artificial tissue scaffolds with biomimicking mechanical properties, particularly for soft tissues.

Computer-aided design and additive manufacturing of bone scaffolds for tissue engineering: state of the art

Tissue Engineering (TE) applications are focused on the design and fabrication of computer-aided artificial bone scaffolds with developing Additive Manufacturing (AM) technologies. Three-dimensional (3D) bone scaffold is designed with Computer-Aided Design (CAD) software, it is controlled pore size, and porosity ratio and a systematic production process are followed. In this study, artificial bone scaffold design and manufacturing technologies developed with AM technology have been discussed. The first part of the study is the applications materialized through different design methods such as CAD-based design, image-based design, implicit surface design, Topology Optimization (TO), and space-filling curves, which are used in computer-aided artificial bone scaffold design. Secondly, working principles of various AM technologies such as material extrusion and vat photopolymerization, powder bed fusion, material jetting, and direct writing and advantages and limitations of implementing these technologies in TE are also evaluated. Finally, possible future areas of use of the AM technologies in TE are discussed.