Three-dimensional bioprinting of tissue-engineered skin: Biomaterials, fabrication techniques, challenging difficulties, and future directions: A review.

As an emerging new manufacturing technology, Three-dimensional (3D) bioprinting provides the potential for the biomimetic construction of multifaceted and intricate architectures of functional integument, particularly functional biomimetic dermal structures inclusive of cutaneous appendages. Although the tissue-engineered skin with complete biological activity and physiological functions is still cannot be manufactured, it is believed that with the advances in matrix materials, molding process, and biotechnology, a new generation of physiologically active skin will be born in the future. In pursuit of furnishing readers and researchers involved in relevant research to have a systematic and comprehensive understanding of 3D printed tissue-engineered skin, this paper furnishes an exegesis on the prevailing research landscape, formidable obstacles, and forthcoming trajectories within the sphere of tissue-engineered skin, including: (1) the prevalent biomaterials (collagen, chitosan, agarose, alginate, etc.) routinely employed in tissue-engineered skin, and a discerning analysis and comparison of their respective merits, demerits, and inherent characteristics; (2) the underlying principles and distinguishing attributes of various current printing methodologies utilized in tissue-engineered skin fabrication; (3) the present research status and progression in the realm of tissue-engineered biomimetic skin; (4) meticulous scrutiny and summation of the extant research underpinning tissue-engineered skin inform the identification of prevailing challenges and issues.

Polyacrylamide/sodium alginate/sodium chloride photochromic hydrogel with high conductivity, anti-freezing property and fast response for information storage and electronic skin.

Photochromic hydrogels have promising prospects in areas such as wearable device, information encryption technology, optoelectronic display technology, and electronic skin. However, there are strict requirements for the properties of photochromic hydrogels in practical engineering applications, especially in some extreme application environments. The preparation of photochromic hydrogels with high transparency, high toughness, fast response, colour reversibility, excellent electrical conductivity, and anti-freezing property remains a challenge. In this study, a novel photochromic hydrogel (PAAm/SA/NaCl-Mo7) was prepared by loading ammonium molybdate (Mo7) and sodium chloride (NaCl) into a dual-network hydrogel of polyacrylamide (PAAm) and sodium alginate (SA) using a simple one-pot method. PAAm/SA/NaCl-Mo7 hydrogel has excellent conductivity (175.9 S/cm), water retention capacity and anti-freezing properties, which can work normally at a low temperature of -28.4 °C. In addition, the prepared PAAm/SA/NaCl-Mo7 hydrogel exhibits fast response (<15 s), high transparency (>70 %), good toughness (maximum elongation up to 1500 %), good cyclic compression properties at high compressive strains (60 %), good biocompatibility (78.5 %), stable reversible discolouration and excellent sensing properties, which can be used for photoelectric display, information storage and motion monitoring. This work provides a new inspiration for the development of flexible electronic skin devices.

Modification, 3D printing process and application of sodium alginate based hydrogels in soft tissue engineering: A review.

Sodium alginate (SA) is an inexpensive and biocompatible biomaterial with fast and gentle crosslinking that has been widely used in biological soft tissue repair/regeneration. Especially with the advent of 3D bioprinting technology, SA hydrogels have been applied more deeply in tissue engineering due to their excellent printability. Currently, the research on material modification, molding process and application of SA-based composite hydrogels has become a hot topic in tissue engineering, and a lot of fruitful results have been achieved. To better help readers have a comprehensive understanding of the development status of SA based hydrogels and their molding process in tissue engineering, in this review, we summarized SA modification methods, and provided a comparative analysis of the characteristics of various SA based hydrogels. Secondly, various molding methods of SA based hydrogels were introduced, the processing characteristics and the applications of different molding methods were analyzed and compared. Finally, the applications of SA based hydrogels in tissue engineering were reviewed, the challenges in their applications were also analyzed, and the future research directions were prospected. We believe this review is of great helpful for the researchers working in biomedical and tissue engineering.

Success Factors of Additive Manufactured Root Analogue Implants.

Dental implantation is an effective method for the treatment of loose teeth, but the threaded dental implants used in the clinic cannot match with the tooth extraction socket. A root analogue implant (RAI) has the congruence shape, which reduces the damage to bone and soft tissue. Additive manufacturing (AM) technologies have the advantages of high precision, flexibility, and easy operation, becoming the main manufacturing method of RAI in basic research. The purpose of this systematic review is to summarize AM technologies used for RAI manufacturing as well as the factors affecting successful implantation. First, it introduces the AM technologies according to different operating principles and summarizes the advantages and disadvantages of each method. Then the influences of materials, structure design, surface characteristics, implant site, and positioning are discussed, providing reference for designers and dentists. Finally, it addresses the gap between basic research and clinical application for additive manufactured RAIs and discusses the current challenges and future research directions for this field.

A 3D printable, highly stretchable, self-healing hydrogel-based sensor based on polyvinyl alcohol/sodium tetraborate/sodium alginate for human motion monitoring.

Self-healing hydrogels have great application potential in the field of bio-sensors due to their self-healing, flexibility and excellent tensile properties. However, most hydrogel-based sensors are processed by template method, which is unable to fabricate complex three-dimensional (3D) structures, and limits the development of hydrogel-based sensor devices. A simple yet efficient one-pot method was proposed to fabricate polyvinyl alcohol/sodium tetraborate/sodium alginate hydrogel inks (SPB), also a fabricating process of self-healing hydrogel based on 3D printing technology has been proposed. The SPB hydrogel rapidly healed (<30 s) at room temperature, while its mechanical properties and conductivity also recovered quickly after healing. Besides, it could be used as wearable strain sensors, whose high stretchability (>2800 % strain) and sensitivity (gauge factor: 18.56 at 2000 % strain) could not only detect very large stretch deformations, but also detect the tiny pressure changes in the human body, such as finger flexion, knee flexion, and respiration. This study provides a method for the rapid fabrication of complex-structured hydrogel-based sensors, which is helpful for the hydrogel-based sensor applications in human motion detection and wearable devices.

Molecular mechanisms in compatibility and mechanical properties of Polyacrylamide/Polyvinyl alcohol blends.

The objectives of this study were to develop a computational model based on molecular dynamics technique to investigate the compatibility and mechanical properties of Polyacrylamide (PAM)/Polyvinyl alcohol (PVA) blends. Five simulation models of PAM/PVA with different composition ratios (4/0, 3/1, 2/2, 1/3, 0/4) were constructed and simulated by using molecular dynamics (MD) simulation. The interaction mechanisms of molecular chains in PAM/PVA blend system were elaborated from the aspects of the compatibility, mechanical properties, binding energy and pair correlation function, respectively. The computed values of solubility parameters for PAM and PVA indicate PAM has a good miscibility with PVA. The results of the static mechanical analysis, based on the equilibrium structures of blends with differing component ratios, shows us that the elastic coefficient, engineering modulus, and ductility are increased with the addition of PVA content, which is 4/0 PAM/PVA<3/1 PAM/PVA<2/2 PAM/PVA<1/3 PAM/PVA<0/4 PAM/PVA. Moreover, binding energy results indicate that a stronger interaction exists among PVA molecular chains comparing with PAM molecular chains, which is why the mechanical properties of blend system increasing with the addition of PVA content. Finally, the results of pair correlation functions (PCFs) between polar functional groups and its surrounding hydrogen atoms, indicated they interact with each other mainly by hydrogen bonds, and the strength of three types of polar functional groups has the order of O(-OH)>O(-C=O)>N(-NH2). This further elaborates the root reason why the mechanical properties of blend system increase with the addition of PVA content.

Structural and water diffusion of poly(acryl amide)/poly(vinyl alcohol) blend films: Experiment and molecular dynamics simulations.

To study the effects of composition ratios and temperature on the diffusion of water molecules in PVA/PAM blend films, five simulation models of PVA/PAM with ten water molecules at different composition ratios (4/0, 3/1, 2/2, 1/3, 0/4) were constructed and simulated by using a molecular dynamics (MD) simulation. The diffusion behavior of water molecules in blends were investigated from the aspects of the diffusion coefficient, free volume, pair correlation function (PCF) and trajectories of water molecules, respectively. And the hydrophilicity of blend composite was studied based on the contact angle and equilibrium water content (EWC) of the blend films. The simulation results show that the diffusion coefficient of water molecules and fractional free volume (FFV) of blend membranes increase with the addition of PAM, and a higher temperature can also improve the diffusion of water molecules. Additionally, the analysis of PCFs reveals the main reason why the diffusion coefficient of water in blend system increases with the addition of PAM. The measurement results of contact angle and EWC of blend films indicate that the hydrophilicity of blend films decreases with the addition of PAM, but the EWC of blends increases with the addition of PAM.

Investigating the properties and interaction mechanism of nano-silica in polyvinyl alcohol/polyacrylamide blends at an atomic level.

The nano-silica can be incorporated into polymers for improved mechanical properties. Notably, the interaction between nano-silica and polymer is of a microscopic phenomenon and thus, hard to observe and study by using experimental methods. Based on molecular dynamics, this paper presents a study on the properties and the interaction mechanism of nano-silica in the polyvinyl alcohol (PVA)/polyacrylamide (PAM) blends at an atomic level. Specifically, six blends of PVA/PAM with varying concentrations of nano-silica (0-13wt%) and two interfacial interaction models of polymers on the silica surface were designed and analyzed at an atomic level in terms of concentration profile, mechanical properties, fractional free volume (FFV), dynamic properties of polymers and X-ray diffraction patterns. The concentration profile results and micromorphologies of equilibrium models suggest PAM molecular chains are easier to be adsorbed on the silica surface than PVA molecular chains in blends. The incorporation of nano-silica into the PVA/PAM blends can increase the blend mechanical properties, densities, and semicrystalline character. Meanwhile, the FFV and the mobility of polymer chain decrease with the silica concentration, which agrees with the results of mechanical properties, densities, and semicrystalline character. Our results also illustrate that an analysis of binding energies and pair correlation functions (PCF) allows for the discovery of the interaction mechanism of nano-silica in PVA/PAM blends; and that hydrogen bond interactions between polar functional groups of polymer molecular chains and the hydroxyl groups of the silica surface are involved in adsorption of the polymers on the silica surface, thus affecting the interaction mechanism of nano-silica in PVA/PAM blend systems.

3D fabrication and characterization of phosphoric acid scaffold with a HA/ß-TCP weight ratio of 60:40 for bone tissue engineering applications.

A key requirement for three-dimensional printing (3-DP) at room temperature of medical implants depends on the availability of printable and biocompatible binder-powder systems. Different concentration polyvinyl alcohol (PVA) and phosphoric acid solutions were chosen as the binders to make the artificial stent biocompatible with sufficient compressive strength. In order to achieve an optimum balance between the bioceramic powder and binder solution, the biocompatibility and mechanical properties of these artificial stent samples were tested using two kinds of binder solutions. This study demonstrated the printable binder formulation at room temperature for the 3D artificial bone scaffolds. 0.6 wt% PVA solution was ejected easily via inkjet printing, with a supplementation of 0.25 wt% Tween 80 to reduce the surface tension of the polyvinyl alcohol solution. Compared with the polyvinyl alcohol scaffolds, the phosphoric acid scaffolds had better mechanical properties. Though both scaffolds supported the cell proliferation, the absorbance of the polyvinyl alcohol scaffolds was higher than that of the phosphoric acid scaffolds. The artificial stents with a hydroxyapatite/beta-tricalcium phosphate (HA/ß-TCP) weight ratios of 60:40 depicted good biocompatibility for both scaffolds. Considering the scaffolds' mechanical and biocompatible properties, the phosphoric acid scaffolds with a HA/ß-TCP weight ratio of 60:40 may be the best combination for bone tissue engineering applications.

Study the bonding mechanism of binders on hydroxyapatite surface and mechanical properties for 3DP fabrication bone scaffolds.

In 3DP fabricating artificial bone scaffolds process, the interaction mechanism between binder and bioceramics power determines the microstructure and macro mechanical properties of Hydroxyapatite (HA) bone scaffold. In this study, we applied Molecular Dynamics (MD) methods to investigating the bonding mechanism and essence of binders on the HA crystallographic planes for 3DP fabrication bone scaffolds. The cohesive energy densities of binders and the binding energies, PCFs g(r), mechanical properties of binder/HA interaction models were analyzed through the MD simulation. Additionally, we prepared the HA bone scaffold specimens with different glues by 3DP additive manufacturing, and tested their mechanical properties by the electronic universal testing machine. The simulation results revealed that the relationship of the binding energies between binders and HA surface is consistent with the cohesive energy densities of binders, which is PAM/HA>PVA/HA>PVP/HA. The PCFs g(r) indicated that their interfacial interactions mainly attribute to the ionic bonds and hydrogen bonds which formed between the polar atoms, functional groups in binder polymer and the Ca, -OH in HA. The results of mechanical experiments verified the relationship of Young׳s modulus for three interaction models in simulation, which is PVA/HA>PAM/HA>PVP/HA. But the trend of compressive strength is PAM/HA>PVA/HA>PVP/HA, this is consistent with the binding energies of simulation. Therefore, the Young׳s modulus of bone scaffolds are limited by the Young׳s modulus of binders, and the compressive strength is mainly decided by the viscosity of binder. Finally, the major reasons for differences in mechanical properties between simulation and experiment were found, the space among HA pellets and the incomplete infiltration of glue were the main reasons influencing the mechanical properties of 3DP fabrication HA bone scaffolds. These results provide useful information in choosing binder for 3DP fabrication bone scaffolds and understanding the interaction mechanism between binder and HA bioceramics power.

Study on the Mechanical Properties of Three-Dimensional Directly Binding Hydroxyapatite Powder.

In the three-dimensional directly fabricating hydroxyapatite composite artificial bone scaffold process, the liquid bio-binder is sprayed on the surface of bioceramics powder layer. The spraying volume and the powder size directly influence the mechanical properties of the bone scaffold and the future biodegradation performance. When the size of powder is stable, the amount of binder spraying will directly affect the mechanical strength of bone scaffold. In order to figure out the solidification mechanism of α-n-butyl cyanoacrylate (NBCA) bio-binder on the hydroxyapatite (HA) powder layer, the molecular dynamics simulation method is applied to investigate the binding energy shifts between NBCA on HA crystallographic planes. The mechanical properties can be deduced from this methodology; furthermore, the Knoop identification experiments are used to investigate the effective elastic modules of pure HA system and HA/NBCA composite model. Both the simulation and the experiments results elucidate that HA (110) has the highest binding energy with NBCA as the high planar atom density and the mechanical properties of HA/NBCA mixed system are stronger than the pure HA system on three-dimensional crystallographic; in this sense, the bone scaffolds with different strengths could be fabricated by controlling various NBCA binders liquid doses on the surface of HA powder layers during the 3D printing process.

Molecular dynamics simulations for the examination of mechanical properties of hydroxyapatite/ poly α-n-butyl cyanoacrylate under additive manufacturing.

Molecular dynamics (MD) simulations emerged to be a helpful tool in the field of material science. In rapid prototyping artificial bone scaffolds process, the binder spraying volume and mechanism are very important for bone scaffolds mechanical properties. In this study, we applied MD simulations to investigating the binding energy of α-n-butyl cyanoacrylate (NBCA) on Hydroxyapatite (HA) crystallographic planes (001, 100 and 110), and to calculating and analyzing the mechanical properties and radial distribution function of the HA(110)/NBCA mixed system. The simulation results suggested that HA (110) has the highest binding energy with NBCA owing to the high planar atom density, and the mechanical properties of HA(110)/NBCA mixed system is stronger than pure HA system. Therefore, the multi-grade strength bone scaffold could be fabricated through spraying various volume NBCA binders during 3D printing process. By calculating the radial distribution function of HA(110)/NBCA, the essence of the interface interaction were successfully elucidated. The forming situation parameters can be referred to calculation results. There exists a strong interaction between HA crystallographic plane (110) and NBCA, it is mainly derived from the hydrogen bonds between O atoms which connect with C atoms of NBCA and H atoms in HA crystal. Furthermore, a strong adsorption effect can be demonstrated between HA and NBCA.