Fabrication of Biomedical Scaffolds Using Biodegradable Polymers.

Degradable polymers are used widely in tissue engineering and regenerative medicine. Maturing capabilities in additive manufacturing coupled with advances in orthogonal chemical functionalization methodologies have enabled a rapid evolution of defect-specific form factors and strategies for designing and creating bioactive scaffolds. However, these defect-specific scaffolds, especially when utilizing degradable polymers as the base material, present processing challenges that are distinct and unique from other classes of materials. The goal of this review is to provide a guide for the fabrication of biodegradable polymer-based scaffolds that includes the complete pathway starting from selecting materials, choosing the correct fabrication method, and considering the requirements for tissue specific applications of the scaffold.

Programmed assembly of oppositely charged homogeneously decorated and Janus particles.

The exploitation of colloidal building blocks with morphological and functional anisotropy facilitates the generation of complex structures with unique properties, which are not exhibited by isotropic particle assemblies. Herein, we demonstrate an easy and scalable bottom-up approach for the programmed assembly of hairy oppositely charged homogeneously decorated and Janus particles based on electrostatic interactions mediated by polyelectrolytes grafted onto their surface. Two different assembly routes are proposed depending on the target structures: raspberry-like/half-raspberry-like or dumbbell-like micro-clusters. Ultimately, stable symmetric and asymmetric micro-structures could be obtained in a well-controlled manner for the homogeneous-homogeneous and homogeneous-Janus particle assemblies, respectively. The spatially separated functionalities of the asymmetric Janus particle-based micro-clusters allow their further assembly into complex hierarchical constructs, which may potentially lead to the design of materials with tailored plasmonics and optical properties.

New insight into icing and de-icing properties of hydrophobic and hydrophilic structured surfaces based on core-shell particles.

Icing is an important problem, which often leads to emergency situations in northern countries. The reduction of icing requires a detailed understanding of this process. In this work, we report on a systematic investigation of the effects of geometry and chemical properties of surfaces on the formation of an ice layer, its properties, and thawing. We compare in detail icing and ice thawing on flat and rough hydrophilic and hydrophobic surfaces. We also show advantages and disadvantages of the surfaces of each kind. We demonstrate that water condenses in a liquid form, leading to the formation of a thin continuous water layer on a hydrophilic surface. Meanwhile, separated rounded water droplets are formed on hydrophobic surfaces. As a result of slower heat exchange, the freezing of rounded water droplets on a hydrophobic surface occurs later than the freezing of the continuous water layer on a hydrophilic one. Moreover, growth of ice on hydrophobic surfaces is slower than on the hydrophilic ones, because ice grows due to the condensation of water vapor on already formed ice crystals, and not due to the condensation on the polymer surface. Rough hydrophobic surfaces also demonstrate a very low ice adhesion value, which is because of the reduced contact area with ice. The main disadvantage of hydrophobic and superhydrophobic surfaces is the pinning of water droplets on them after thawing. Flat hydrophilic poly(ethylene glycol)-modified surfaces also exhibit very low ice adhesion, which is due to the very low freezing point of the water-poly(ethylene glycol) mixtures. Water easily leaves from flat hydrophilic poly(ethylene glycol)-modified surfaces, and they quickly become dry. However, the ice growth rate on poly(ethylene glycol)-modified hydrophilic surfaces is the highest. These results indicate that neither purely (super)hydrophobic polymeric surfaces, nor "antifreeze" hydrophilic ones provide an ideal solution to the problem of icing.

Bioprinting: Mechanical Stabilization and Reinforcement Strategies in Regenerative Medicine.

Bioprinting describes the printing of biomaterials and cell-laden or cell-free hydrogels with various combinations of embedded bioactive molecules. It encompasses the precise patterning of biomaterials and cells to create scaffolds for different biomedical needs. There are many requirements that bioprinting scaffolds face, and it is ultimately the interplay between the scaffold's structure, properties, processing, and performance that will lead to its successful translation. Among the essential properties that the scaffolds must possess-adequate and appropriate application-specific chemical, mechanical, and biological performance-the mechanical behavior of hydrogel-based bioprinted scaffolds is the key to their stable performance in vivo at the site of implantation. Hydrogels that typically constitute the main scaffold material and the medium for the cells and biomolecules are very soft, and often lack sufficient mechanical stability, which reduces their printability and, therefore, the bioprinting potential. The aim of this review article is to highlight the reinforcement strategies that are used in different bioprinting approaches to achieve enhanced mechanical stability of the bioinks and the printed scaffolds. Enabling stable and robust materials for the bioprinting processes will lead to the creation of truly complex and remarkable printed structures that could accelerate the application of smart, functional scaffolds in biomedical settings. Impact statement Bioprinting is a powerful tool for the fabrication of 3D structures and scaffolds for biomedical applications. It has gained tremendous attention in recent years, and the bioink library is expanding to include more and more material combinations. From the practical application perspective, different properties need to be considered, such as the printed structure's chemical, mechanical, and biological performances. Among these, the mechanical behavior of the printed constructs is critical for their successful translation into the clinic. The aim of this review article is to explore the different reinforcement strategies used for the mechanical stabilization of bioinks and bioprinted structures.

Tensile performance data of 3D printed photopolymer gyroid lattices.

Additive manufacturing has provided the ability to manufacture complex structures using a wide variety of materials and geometries. Structures such as triply periodic minimal surface (TPMS) lattices have been incorporated into products across many fields due to their unique combinations of mechanical, geometric, and physical properties. Yet, the near limitless possibility of combining geometry and material into these lattices leaves much to be discovered. This article provides a dataset of experimentally gathered tensile stress-strain curves and measured porosity values for 389 unique gyroid lattice structures manufactured using vat photopolymerization 3D printing. The lattice samples were printed from one of twenty different photopolymer materials available from either Formlabs, LOCTITE AM, or ETEC that range from strong and brittle to elastic and ductile and were printed on commercially available 3D printers, specifically the Formlabs Form2, Prusa SL1, and ETEC Envision One cDLM Mechanical. The stress-strain curves were recorded with an MTS Criterion C43.504 mechanical testing apparatus and following ASTM standards, and the void fraction or "porosity" of each lattice was measured using a calibrated scale. This data serves as a valuable resource for use in the development of novel printing materials and lattice geometries and provides insight into the influence of photopolymer material properties on the printability, geometric accuracy, and mechanical performance of 3D printed lattice structures. The data described in this article was used to train a machine learning model capable of predicting mechanical properties of 3D printed gyroid lattices based on the base mechanical properties of the printing material and porosity of the lattice in the research article [1].

Thiol-Based Three-Dimensional Printing of Fully Degradable Poly(propylene fumarate) Star Polymers.

Poly(propylene fumarate) star polymers photochemically 3D printed with degradable thiol cross-linkers yielded highly tunable biodegradable polymeric materials. Tailoring the alkene:thiol ratio (5:1, 10:1, 20:1 and 30:1) and thus the cross-link density within the PPF star systems yielded a wide variation of both the mechanical and degradation properties of the printed materials. Fundamental trends were established between the polymer network cross-link density, glass transition temperature, and tensile and thermomechanical properties of the materials. The tensile properties of the PPF star-based systems were compared to commercial state-of-the-art non-degradable polymer resins. The thiolene-cross-linked materials are fully degradable and possess properties over a wide range of mechanical properties relevant to regenerative medicine applications.

Arene-perfluoroarene interactions confer enhanced mechanical properties to synthetic nanotubes.

Supramolecular nanotubes prepared through macrocycle assembly offer unique properties that stem from their long-range order, structural predictability, and tunable microenvironments. However, assemblies that rely on weak non-covalent interactions often have limited aspect ratios and poor mechanical integrity, which diminish their utility. Here pentagonal imine-linked macrocycles are prepared by condensing a pyridine-containing diamine and either terephthalaldehyde or 2,3,5,6-tetrafluoroterephthalaldehyde. Atomic force microscopy and synchrotron in solvo X-ray diffraction demonstrate that protonation of the pyridine groups drives assembly into high-aspect ratio nanotube assemblies. A 1 : 1 mixture of each macrocycle yielded nanotubes with enhanced crystallinity upon protonation. UV-Vis and fluorescence spectroscopy indicate that nanotubes containing both arene and perfluoroarene subunits display spectroscopic signatures of arene-perfluoroarene interactions. Touch-spun polymeric fibers containing assembled nanotubes prepared from the perhydro- or perfluorinated macrocycles exhibited Young's moduli of 1.09 and 0.49 GPa, respectively. Fibers containing nanotube assemblies reinforced by arene-perfluoroarene interactions yielded a 93% increase in the Young's modulus over the perhydro derivative, up to 2.1 GPa. These findings demonstrate that tuning the chemical composition of the monomeric macrocycles can have profound effects on the mechanical strength of the resulting assemblies. More broadly, these results will inspire future studies into tuning orthogonal non-covalent interactions between macrocycles to yield nanotubes with emergent functions and technological potential.

Reinforcement and Fatigue of a Bioinspired Mineral-Organic Bioresorbable Bone Adhesive.

Bioresorbable bone adhesives may provide remarkable clinical solutions in areas ranging from fixation and osseointegration of permanent implants to the direct healing and fusion of bones without permanent fixation hardware. Mechanical properties of bone adhesives are critical for their successful application in vivo. Reinforcement of a tetracalcium phosphate-phosphoserine bone adhesive is investigated using three degradable reinforcement strategies: poly(lactic-co-glycolic) (PLGA) fibers, PLGA sutures, and chitosan lactate. All three approaches lead to higher compressive strengths of the material and better fatigue performance. Reinforcement with PLGA fibers and chitosan lactate results in a 100% probability of survival of samples at 20 MPa maximum compressive stress level, which is almost ten times higher compared to compressive loads observed in the intervertebral discs of the spine in vivo. High adhesive shear strength of 5.1 MPa is achieved for fiber-reinforced bone adhesive by tuning the surface architecture of titanium samples. Finally, biological and biomechanical performance of the fiber-reinforced adhesive is evaluated in a rabbit distal femur osteotomy model, showing the potential of the bone adhesive for clinical use.

High-Strength Hydrogel Attachment through Nanofibrous Reinforcement.

The repair of a cartilage lesion with a hydrogel requires a method for long-term fixation of the hydrogel in the defect site. Attachment of a hydrogel to a base that allows for integration with bone can enable long-term fixation of the hydrogel, but current methods of forming bonds to hydrogels have less than a tenth of the shear strength of the osteochondral junction. This communication describes a new method, nanofiber-enhanced sticking (NEST), for bonding a hydrogel to a base with an adhesive shear strength three times larger than the state-of-the-art. An example of NEST is described in which a nanofibrous bacterial cellulose sheet is bonded to a porous base with a hydroxyapatite-forming cement followed by infiltration of the nanofibrous sheet with hydrogel-forming polymeric materials. This approach creates a mineralized nanofiber bond that mimics the structure of the osteochondral junction, in which collagen nanofibers extend from cartilage into a mineralized region that anchors cartilage to bone.

Shape-changing polymers for biomedical applications.

Smart polymers that are capable of controlled shape transformations under external stimuli have attracted significant attention in the recent years due to the resemblance of this behavior to the biological intelligence observed in nature. Moreover, shape-morphing polymer-based materials are great candidates for biomedical applications due to their adaptive properties, controlled shape transformations, and enriched functionality. In this review, we focus on the recent progress in the field of shape-memory and shape-changing polymers, highlighting their most promising applications in the biomedical field. We include a brief theoretical background on the underlying molecular mechanisms, classification of the polymer systems based on their mechanical properties, and the most promising state-of-the-art processing techniques for the fabrication of intelligent polymer-based materials. The aim of this review is to provide a link between the diverse stimuli-responsive polymer systems and their mechanical properties, and to highlight the most appealing up-to-date biomedical applications for shape-morphing systems.

Hybrid Janus Particles: Challenges and Opportunities for the Design of Active Functional Interfaces and Surfaces.

Janus particles are a unique class of multifunctional patchy particles combining two dissimilar chemical or physical functionalities at their opposite sides. The asymmetry characteristic for Janus particles allows them to self-assemble into sophisticated structures and materials not attainable by their homogeneous counterparts. Significant breakthroughs have recently been made in the synthesis of Janus particles and the understanding of their assembly. Nevertheless, the advancement of their applications is still a challenging field. In this Review, we highlight recent developments in the use of Janus particles as building blocks for functional materials. We provide a brief introduction into the synthetic strategies for the fabrication of JPs and their properties and assembly, outlining the existing challenges. The focus of this Review is placed on the applications of Janus particles for active interfaces and surfaces. Active functional interfaces are created owing to the stabilization efficiency of Janus particles combined with their capability for interface structuring and functionalizing. Moreover, Janus particles can be employed as building blocks to fabricate active functional surfaces with controlled chemical and topographical heterogeneity. Ultimately, we will provide implications for the rational design of multifunctional materials based on Janus particles.

Bioinspired Mineral-Organic Bioresorbable Bone Adhesive.

Bioresorbable bone adhesives have potential to revolutionize the clinical treatment of the human skeletal system, ranging from the fixation and osteointegration of permanent implants to the direct healing and fusion of bones without permanent fixation hardware. Despite an unmet need, there are currently no bone adhesives in clinical use that provide a strong enough bond to wet bone while possessing good osteointegration and bioresorbability. Inspired by the sandcastle worm that creates a protective tubular shell around its body using a proteinaceous adhesive, a novel bone adhesive is introduced, based on tetracalcium phosphate and phosphoserine, that cures in minutes in an aqueous environment and provides high bone-to-bone adhesive strength. The new material is measured to be 10 times more adhesive than bioresorbable calcium phosphate cement and 7.5 times more adhesive than non-resorbable poly(methyl methacrylate) bone cement, both of which are standard of care in the clinic today. The bone adhesive also demonstrates chemical adhesion to titanium approximately twice that of its adhesion to bone, unlocking the potential for adherence to metallic implants during surrounding bony incorporation. Finally, the bone adhesive is shown to demonstrate osteointegration and bioresorbability over a 52-week period in a critically sized distal femur defect in rabbits.

4D Biofabrication Using Shape-Morphing Hydrogels.

Despite the tremendous potential of bioprinting techniques toward the fabrication of highly complex biological structures and the flourishing progress in 3D bioprinting, the most critical challenge of the current approaches is the printing of hollow tubular structures. In this work, an advanced 4D biofabrication approach, based on printing of shape-morphing biopolymer hydrogels, is developed for the fabrication of hollow self-folding tubes with unprecedented control over their diameters and architectures at high resolution. The versatility of the approach is demonstrated by employing two different biopolymers (alginate and hyaluronic acid) and mouse bone marrow stromal cells. Harnessing the printing and postprinting parameters allows attaining average internal tube diameters as low as 20 µm, which is not yet achievable by other existing bioprinting/biofabrication approaches and is comparable to the diameters of the smallest blood vessels. The proposed 4D biofabrication process does not pose any negative effect on the viability of the printed cells, and the self-folded hydrogel-based tubes support cell survival for at least 7 d without any decrease in cell viability. Consequently, the presented 4D biofabrication strategy allows the production of dynamically reconfigurable architectures with tunable functionality and responsiveness, governed by the selection of suitable materials and cells.

Hybrid Hairy Janus Particles as Building Blocks for Antibiofouling Surfaces.

Herein, we report a new strategy for the design of antifouling surfaces by using hybrid hairy Janus particles. The amphiphilic Janus particles possess either a spherical or a plateletlike shape and have core-shell structures with an inorganic core and hydrophilic/hydrophobic polymeric shells. Subsequently, these bifunctional Janus particles enable the fabrication of surfaces with modularity in chemical composition and final surface topography, which possess antifouling properties. The antifouling and fouling-release capability of the composite Janus particle-based surfaces is investigated using the marine biofilm-forming bacteria Cobetia marina. The Janus particle-based coatings are robust and significantly reduce bacterial retention under both static and dynamic conditions independent of the particle geometry. The plateletlike (kaolinite-based) Janus particles represent a scalable system for the rational design of antifouling coatings as well as their large-scale production and application in the future.

Hybrid Hairy Janus Particles Decorated with Metallic Nanoparticles for Catalytic Applications.

We report for the first time on the design of an advanced hairy hybrid Janus-type catalyst, which is comprised of an inorganic silica core covered with two distinct polymeric shells (hydrophilic and hydrophobic) on its opposite sides, while the catalytic species (in our case silver or gold nanoparticles) are immobilized directly into the hydrophilic stimuli-responsive polymer shell. The primary 200 nm large Janus particles with poly(acrylic acid) serving as the hydrophilic and polystyrene as the hydrophobic polymer were synthesized through a Pickering emulsion and a combination of "grafting from"/"grafting to" approaches. The incorporation of silver and gold nanoparticles within the hydrophilic polymer shell was achieved by infiltrating the respective metal ions into the polymer matrix, and nanoparticles were formed upon the addition of a reducing agent (triethylamine). Plasmon absorptions typical for silver and gold nanostructures were observed on the functionalized Janus particles using UV-vis spectroscopy. The respective systems were investigated by TEM and cryo-TEM revealing that the incorporated nanoparticles are selectively localized on the poly(acrylic acid) side of the Janus particles. The efficiency of the catalyst as well as the accessibility of the incorporated nanoparticles was tested on the reduction of Methylene Blue, Eosin Y, and 4-nitrophenol as convenient benchmark systems. Ultimately, the hairy Janus particles with immobilized Ag or Au nanoparticles efficiently catalyzed the respective reactions by applying extremely low amounts of catalyst. Finally, we demonstrated several advantages of the use of JPs with immobilized metallic nanoparticles, which are (i) JPs stabilize the emulsions, (ii) the emulsion can be destabilized by utilizing responsive properties of the JPs, and (iii) JPs can easily be recovered after reaction and reused again.

Platelet Janus particles with hairy polymer shells for multifunctional materials.

A novel approach is developed for the large-scale synthesis of Janus particles with platelet geometry and dense polymer shells by employing simultaneous "grafting from" of hydrophilic and hydrophobic polymers using surface-induced ATRP in emulsion. The method is based on the fabrication of an emulsion consisting of a water solution of a hydrophilic monomer and a solution of a hydrophobic monomer in an organic solvent, which is stabilized by initiator-modified kaolinite particles. Two polymers are grafted simultaneously on the opposite faces of the kaolinite particle during polymerization. The synthesized particles have a clear Janus character and are highly efficient for the stabilization of emulsions. Because of its simplicity, the method can readily be upscaled for the synthesis of large amounts of Janus particles, up to several grams.