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Biodegradable polymers derived from renewable resources can be interesting materials for a plethora of applications and have therefore gained increased interest over the last decades. We herein report for the first time the synthesis of random copolymers based on lactic and mandelic acid via ring-opening-polymerisation of their corresponding O-carboxyanhydrides (OCA). Copolymers with tailored glass transition temperature and degradation time were obtained by adjusting the co-monomer feed during copolymerisation. Molecular weight analyses of the obtained copolymers indicated lower molecular weights in comparison to the target values. Our hypothesis that keto-enol tautomerisation of the OCA-monomers was the cause for this anomaly was substantiated by a mechanistic study of the OCA-polymerization reaction using lacOCA and manOCA as case study.

One drawback of thiol-ene mixtures is their poor shelf-life (due to a lack of stability) which limits their use in certain applications for which the compounds have to retain their activity (i.e. unreacted) for long time periods. To address this issue, the present work reports on the synthesis of a cross-linker containing a thiol group in a protected form (i.e. thioacetate). The conversion of the thioacetate groups into the corresponding thiol moieties after alkaline treatment was monitored by 1H NMR spectroscopy. The results showed that the thioacetate groups could be deprotected within 300 min using sodium hydroxide or ammonium hydroxide. Subsequently, the synthesized thioacetate cross-linker was combined with an acrylate-based compound to form a cross-linked network in a one-pot process via sequential deprotection into a thiol and subsequent thiol-ene Michael-type addition. In-situ gel formation in a one pot-process was only achieved in the presence of ammonium hydroxide as sodium hydroxide causes hydrolysis of the cross-linkable acrylate moieties.

Nowadays, breast implants, lipofilling, and microsurgical free tissue transfer are the most often applied procedures to repair soft tissue defects resulting from mastectomies/lumpectomies following breast cancer. Due to the drawbacks and limitations associated with these conventional clinical practices, there is a need for alternative reconstructive strategies. The development of biomimetic materials able to promote cell proliferation and adipogenic differentiation has gained increasing attention in the context of adipose reconstructive purposes. Herein, thiol-norbornene crosslinkable gelatin-based materials were developed and benchmarked to the current commonly applied methacryloyl-modified gelatin (GelMA) with different degrees of substitutions focussing on bottom-up tissue engineering. The developed hydrogels resulted in similar gel fractions, swelling, and in vitro biodegradation properties compared to the benchmark materials. Furthermore, the thiol-ene hydrogels exhibited mechanical properties closer to those of native fatty tissue compared to GelMA. The mechanical cues of the equimolar GelNB DS55% + GelSH DS75% composition resulted not only in similar biocompatibility but also, more importantly, in superior differentiation of the encapsulated cells into the adipogenic lineage, as compared to GelMA. It can be concluded that the photo-crosslinkable thiol-ene systems offer a promising strategy toward adipose tissue engineering through cell encapsulation compared to the benchmark GelMA.

Overuse tendon injuries are a major cause of musculoskeletal morbidity in both human and equine athletes, due to the cumulative degenerative damage. These injuries present significant challenges as the healing process often results in the formation of inferior scar tissue. The poor success with conventional therapy supports the need to search for novel treatments to restore functionality and regenerate tissue as close to native tendon as possible. Mesenchymal stem cell (MSC)-based strategies represent promising therapeutic tools for tendon repair in both human and veterinary medicine. The translation of tissue engineering strategies from basic research findings, however, into clinical use has been hampered by the limited understanding of the multifaceted MSC mechanisms of action. In vitro models serve as important biological tools to study cell behavior, bypassing the confounding factors associated with in vivo experiments. Controllable and reproducible in vitro conditions should be provided to study the MSC healing mechanisms in tendon injuries. Unfortunately, no physiologically representative tendinopathy models exist to date. A major shortcoming of most currently available in vitro tendon models is the lack of extracellular tendon matrix and vascular supply. These models often make use of synthetic biomaterials, which do not reflect the natural tendon composition. Alternatively, decellularized tendon has been applied, but it is challenging to obtain reproducible results due to its variable composition, less efficient cell seeding approaches and lack of cell encapsulation and vascularization. The current review will overview pros and cons associated with the use of different biomaterials and technologies enabling scaffold production. In addition, the characteristics of the ideal, state-of-the-art tendinopathy model will be discussed. Briefly, a representative in vitro tendinopathy model should be vascularized and mimic the hierarchical structure of the tendon matrix with elongated cells being organized in a parallel fashion and subjected to uniaxial stretching. Incorporation of mechanical stimulation, preferably uniaxial stretching may be a key element in order to obtain appropriate matrix alignment and create a pathophysiological model. Together, a thorough discussion on the current status and future directions for tendon models will enhance fundamental MSC research, accelerating translation of MSC therapies for tendon injuries from bench to bedside.

The limited penetration depth of visible light in biological tissues has encouraged researchers to develop novel implantable light-guiding devices. Optical fibers and waveguides that are made from biocompatible and biodegradable materials offer a straightforward but effective approach to overcome this issue. In the last decade, various optically transparent biomaterials, as well as different fabrication techniques, have been investigated for this purpose, and in view of obtaining fully fledged optical fibers. This article reviews the state-of-the-art in the development of biocompatible and biodegradable optical fibers. Whilst several reviews that focus on the chemical properties of the biomaterials from which these optical waveguides can be made have been published, a systematic review about the actual optical fibers made from these materials and the different fabrication processes is not available yet. This prompted us to investigate the essential properties of these biomaterials, in view of fabricating optical fibers, and in particular to look into the issues related to fabrication techniques, and also to discuss the challenges in the use and operation of these optical fibers. We close our review with a summary and an outline of the applications that may benefit from these novel optical waveguides.

(1) Background: Tendinopathy is a common injury in both human and equine athletes. Representative in vitro models are mandatory to facilitate translation of fundamental research into successful clinical treatments. Natural biomaterials like gelatin provide favorable cell binding characteristics and are easily modifiable. In this study, methacrylated gelatin (gel-MA) and norbornene-functionalized gelatin (gel-NB), crosslinked with 1,4-dithiotreitol (DTT) or thiolated gelatin (gel-SH) were compared. (2) Methods: The physicochemical properties (1H-NMR spectroscopy, gel fraction, swelling ratio, and storage modulus) and equine tenocyte characteristics (proliferation, viability, and morphology) of four different hydrogels (gel-MA, gel-NB85/DTT, gel-NB55/DTT, and gel-NB85/SH75) were evaluated. Cellular functionality was analyzed using fluorescence microscopy (viability assay and focal adhesion staining). (3) Results: The thiol-ene based hydrogels showed a significantly lower gel fraction/storage modulus and a higher swelling ratio compared to gel-MA. Significantly less tenocytes were observed on gel-MA discs at 14 days compared to gel-NB85/DTT, gel-NB55/DTT and gel-NB85/SH75. At 7 and 14 days, the characteristic elongated morphology of tenocytes was significantly more pronounced on gel-NB85/DTT and gel-NB55/DTT in contrast to TCP and gel-MA. (4) Conclusions: Thiol-ene crosslinked gelatins exploiting DTT as a crosslinker are the preferred biomaterials to support the culture of tenocytes. Follow-up experiments will evaluate these biomaterials in more complex models.

This research aims at developing a more potent solution for deep flexor tendon repair by combining a mechanical and biological approach. A reinforced, multi-layered electrospun tubular construct is developed, composed of three layers: an inner electrospun layer containing an anti-inflammatory component (Naproxen), a middle layer of braided monofilament as reinforcement and an outer electrospun layer containing an anti-adhesion component (hyaluronic acid, HA). In a first step, a novel acrylate endcapped urethane-based precursor (AUP) is developed and characterized by measuring molar mass, acrylate content and thermo-stability. The AUP material is benchmarked against commercially available poly(ε-caprolactone) (PCL). Next, the materials are processed into multi-layered, tubular constructs with bio-active components (Naproxen and HA) using electrospinning. In vitro assays using human fibroblasts show that incorporation of the bio-active components is successful and not-cytotoxic. Moreover, tensile testing using ex vivo sheep tendons prove that the developed multi-layered constructs fulfill the required strength for tendon repair (i.e. 2.79-3.98 MPa), with an ultimate strength of 8.56 ± 1.92 MPa and 8.36 ± 0.57 MPa for PCL and AUP/PCL constructs respectively. In conclusion, by combining a mechanical approach (improved mechanical properties) with the incorporation of bio-active compounds (biological approach), this solution shows its potential for application in deep flexor tendon repair. ispartof: Materials Science and Engineering: C vol:119 ispartof: location:Netherlands status: Published online

Tissue engineering is an elegant tool to create organs in vitro, that can help obviate the lack of organ donors in transplantation medicine and provide the opportunity of studying complex biological systems in vitro, thereby reducing the need for animal experiments. Artificial intestine models are at the core of Fish-AI, an EU FET-Open research project dedicated to the development of a 3D in vitro platform that is intended to enable the aquaculture feed industry to predict the nutritional and health value of alternative feed sources accurately and efficiently.At present, it is impossible to infer the health and nutrition value through the chemical characterization of any given feed. Therefore, each new feed must be tested through in vivo growth trials. The procedure is lengthy, expensive and requires the use of many animals. Furthermore, although this process allows for a precise evaluation of the final effect of each feed, it does not improve our basic knowledge of the cellular and molecular mechanisms determining such end-results. In turn, this lack of mechanistic knowledge severely limits the capacity to understand and predict the biological value of a single raw material and of their different combinations.The protocol described herein allows to develop the two main components essential to produce a functional platform for the efficient and reliable screening of feeds that the feed industry is currently developing for improving their health and nutritional value. It is here applied to the Rainbow Trout, but it can be fruitfully used to many other fish species.

‘Organ-on-chip’ devices which integrate three-dimensional (3D) cell culture techniques with microfluidic approaches have the capacity to overcome the limitations of classical 2D platforms. Although several different strategies have been developed to improve the angiogenesis within hydrogels, one of the main challenges in tissue engineering remains the lack of vascularization in the fabricated 3D models. The present work focuses on the high-definition (HD) bioprinting of microvascular structures directly on-chip using two-photon polymerization (2PP). 2PP is a nonlinear process, where the near-infrared laser irradiation will only lead to the polymerization of a very small volume pixel (voxel), allowing the fabrication of channels in the microvascular range (10–30 µm in diameter). Additionally, 2PP not only enables the fabrication of sub-micrometer resolution scaffolds but also allows the direct embedding of cells within the produced structure. The accuracy of the 2PP printing parameters were optimized in order to achieve high-throughput and HD production of microfluidic vessel-on-chip platforms. The spherical aberrations stemming from the refractive index mismatch and the focusing depth inside the sample were simulated and the effect of the voxel compensation as well as different printing modes were demonstrated. Different layer spacings and their dependency on the applied laser power were compared both in terms of accuracy and required printing time resulting in a 10-fold decrease in structuring time while yielding well-defined channels of small diameters. Finally, the capacity of 2PP to create vascular structures within a microfluidic chip was tested with two different settings, by direct embedding of a co-culture of endothelial- and supporting cells during the printing process and by creating a supporting, cell-containing vascular scaffold barrier where the endothelial cell spheroids can be seeded afterwards. The functionality of the formed vessels was demonstrated with immunostaining of vascular endothelial cadherin (VE-Cadherin) endothelial adhesion molecules in both static and perfused culture.

Various biopolymers, including gelatin, have already been applied to serve a plethora of tissue engineering purposes. However, substantial concerns have arisen related to the safety and the reproducibility of these materials due to their animal origin and the risk associated with pathogen transmission as well as batch-to-batch variations. Therefore, researchers have been focusing their attention toward recombinant materials that can be produced in a laboratory with full reproducibility and can be designed according to specific needs (e.g., by introducing additional RGD sequences). In the present study, a recombinant protein based on collagen type I (RCPhC1) was functionalized with photo-cross-linkable methacrylamide (RCPhC1-MA), norbornene (RCPhC1-NB), or thiol (RCPhC1-SH) functionalities to enable high-resolution 3D printing via two-photon polymerization (2PP). The results indicated a clear difference in 2PP processing capabilities between the chain-growth-polymerized RCPhC1-MA and the step-growth-polymerized RCPhC1-NB/SH. More specifically, reduced swelling-related deformations resulting in a superior CAD-CAM mimicry were obtained for the RCPhC1-NB/SH hydrogels. In addition, RCPhC1-NB/SH allowed the processing of the material in the presence of adipose tissue-derived stem cells that survived the encapsulation process and also were able to proliferate when embedded in the printed structures. As a consequence, it is the first time that successful HD bioprinting with cell encapsulation is reported for recombinant hydrogel bioinks. Therefore, these results can be a stepping stone toward various tissue engineering applications.

Photocrosslinkable gelatin hydrogels are excellent bioinks or biomaterial ink components to serve biofabrication applications. Especially the widely investigated gelatin-methacroyl hydrogels hold an impressive track record. However, over the past decade, increasing attention is being paid to thiol-ene photo-click chemistry to obtain hydrogel networks benefitting from a faster reactivity (i.e. seconds vs minutes) along with superior biocompatibility and processability. In order to exploit this photo-click chemistry, often an ene-functionality (e.g.. Norbornene) is introduced onto gelatin followed by crosslinking in the presence of a multifunctional thiol (e.g.. DTT). To date, very limited research has been performed on the influence of the applied thiolated crosslinker on the final hydrogel properties. Therefore, the present work assesses the influence of different thiolated crosslinkers on the crosslinking kinetics, mechanical properties and biological performance of the hydrogels upon encapsulation of primary adipose tissue-derived stem cells in which indicated a cell viability exceeding 70%. Furthermore, the different formulations were processed using two-photon polymerisation which indicated, in addition to differences in processing window and swelling ratio, a previously unreported phenomenon. At high intensities (i.e. ≥ 150 mW), the laser results in cleavage of the gelatin backbone even in the absence of distinct photo-cleavable functionalities. This can have potential to introduce channels or softer regions in gels to result in zones characterized by different degradation speeds or the formation of blood vessels. Consequently, the present study can be used to provide guidance towards tailoring the thiol-ene system towards the desired applications. Creative Commons Attribution license.

To date, the treatment of articular cartilage lesions remains challenging. A promising strategy for the development of new regenerative therapies is hybrid bioprinting, combining the principles of developmental biology, biomaterial science, and 3D bioprinting. In this approach, scaffold-free cartilage microtissues with small diameters are used as building blocks, combined with a photo-crosslinkable hydrogel and subsequently bioprinted. Spheroids of human bone marrow-derived mesenchymal stem cells (hBM-MSC) are created using a high-throughput microwell system and chondrogenic differentiation is induced during 42 days by applying chondrogenic culture medium and low oxygen tension (5%). Stable and homogeneous cartilage spheroids with a mean diameter of 116 ± 2.80 μm, which is compatible with bioprinting, were created after 14 days of culture and a glycosaminoglycans (GAG)- and collagen II-positive extracellular matrix (ECM) was observed. Spheroids were able to assemble at random into a macrotissue, driven by developmental biology tissue fusion processes, and after 72 h of culture, a compact macrotissue was formed. In a directed assembly approach, spheroids were assembled with high spatial control using the bio-ink based extrusion bioprinting approach. Therefore, 14-day spheroids were combined with a photo-crosslinkable methacrylamide-modified gelatin (gelMA) as viscous printing medium to ensure shape fidelity of the printed construct. The photo-initiators Irgacure 2959 and Li-TPO-L were evaluated by assessing their effect on bio-ink properties and the chondrogenic phenotype. The encapsulation in gelMA resulted in further chondrogenic maturation observed by an increased production of GAG and a reduction of collagen I. Moreover, the use of Li-TPO-L lead to constructs with lower stiffness which induced a decrease of collagen I and an increase in GAG and collagen II production. After 3D bioprinting, spheroids remained viable and the cartilage phenotype was maintained. Our findings demonstrate that hBM-MSC spheroids are able to differentiate into cartilage microtissues and display a geometry compatible with 3D bioprinting. Furthermore, for hybrid bioprinting of these spheroids, gelMA is a promising material as it exhibits favorable properties in terms of printability and it supports the viability and chondrogenic phenotype of hBM-MSC microtissues. Moreover, it was shown that a lower hydrogel stiffness enhances further chondrogenic maturation after bioprinting. ispartof: FRONTIERS IN BIOENGINEERING AND BIOTECHNOLOGY vol:8 ispartof: location:Switzerland status: published

To mitigate autogenous shrinkage in cementitious materials and simultaneously preserve the material’s mechanical performance, superabsorbent polymers and nanosilica are included in the mixture design. The use of the specific additives influences both the hydration process and the hardened microstructure, while autogenous healing of cracks can be stimulated. These three stages are monitored by means of non-destructive testing, showing the sensitivity of elastic waves to the occurring phenomena. Whereas the action of the superabsorbent polymers was evidenced by acoustic emission, the use of ultrasound revealed the differences in the developed microstructure and the self-healing of cracks by a comparison with more commonly performed mechanical tests. The ability of NDT to determine these various features renders it a promising measuring method for future characterization of innovative cementitious materials., info:eu-repo/semantics/published

The recent introduction of semicrystalline acrylated oligomers exhibiting fast photoinitiated free radical polymerization in the solid state calls for a deeper understanding of the mechanisms behin...

© 2018 Elsevier Ltd Development of suitable capsules is essential to achieve self-healing by encapsulation. In the context of self-healing concrete, capsules that can be easily mixed into concrete and release the healing agent when cracking occurs are ideally required. The optimization of these properties would allow for a successful implementation at large scale in practical (concrete) applications. In the present work, the suitability of polymeric cylindrical capsules made of poly(methyl methacrylate) (PMMA) to carry healing agent in self-healing concrete has been evaluated. An innovative method to assess more easily the capsules survival during concrete mixing was developed. This method is based on the evaluation of the setting behavior of concrete containing capsules filled with setting accelerator. Capsules with a wall thickness of 0.7 mm were able to resist the concrete mixing process and to rupture at relatively small crack widths (116 μm) after applying a surface treatment to increase the adhesion between the capsules and the cementitious matrix. Next, the self-healing efficiency of the encapsulation materials (glass or PMMA) was evaluated on real-scale concrete beams. The results showed that cracked concrete beams with mixed-in capsules (glass or PMMA) filled with water-repellent agent showed higher resistance against chloride ingress compared to plain cracked concrete beams. PMMA capsules showed a lower self-healing efficiency (in relation to chloride ingress) compared to glass due to a less favorable distribution of the capsules in the concrete. However, concrete containing glass capsules is susceptible towards alkali-silica reaction. Although optimization of the PMMA capsules is still necessary to improve their distribution in concrete and achieve higher self-healing efficiency, the obtained results indicate that these capsules could be a promising solution towards self-healing concrete. ispartof: Cement & Concrete Composites vol:89 pages:260-271 status: published

Superabsorbent polymers (SAPs) based on polysaccharides, especially alginate, could offer a valuable solution in a plethora of applications going from drug delivery to self-healing concrete. This has already been proven with both calcium alginate and methacrylated alginate combined with acrylic acid. In this manuscript, the effect of varying the degree of methacrylation and use of a combination of acrylic acid and acrylamide is investigated to explore the effects on the relevant SAP characteristics. The materials showed high gel fractions and a strong swelling capacity up to 630gwater/gSAP, especially for superabsorbent polymers with a low degree of substitution. The SAPs also showed only a limited hydrolysis in aqueous and cement filtrate solutions. ispartof: CARBOHYDRATE POLYMERS vol:168 pages:44-51 ispartof: location:England status: published

Efficient crosslinking of conventional photoreactive hydrogel precursors relies on the mobility of the reactive groups and is typically addressed from the liquid state. However, this represents a major limitation for many processing techniques of hydrogel materials. Herein, a model precursor is introduced that overcomes this challenge using a prepolymer designed to enable successful crosslinking in the solid state. The precursor is synthesized by connecting a flexible, mono-acrylated spacer to a semi-crystalline hydrophilic backbone polymer using a di-isocyanate linker. The resulting prepolymers exhibit excellent solid-state photoreactivity, even in the absence of a photo-initiator. As a proof of concept, the precursor has successfully been processed by: (1) solution electrospinning with subsequent solid-state photopolymerization (SSPP), (2) melt-based additive manufacturing with subsequent SSPP and (3) two-photon polymerization in the solid state. No cell adhesion takes place on bare crosslinked 3D-printed scaffolds whereas excellent cell adhesion is recovered after application of a gelatin methacrylamide coating. With this novel class of UV-reactive precursors unprecedented hydrogel processing avenues are opened.

Tissue regeneration often occurs only to a limited extent. By providing a three-dimensional matrix serving as a surrogate extracellular matrix that promotes adult stem cell adhesion, proliferation and differentiation, scaffold-guided tissue regeneration aims at overcoming this limitation. In this study, we applied hydrogels made from crosslinkable gelatin, the hydrolyzed form of collagen, and functionalized starch which were characterized in depth and optimized as described in Van Nieuwenhove et al., 2016. "Gelatin- and Starch-Based Hydrogels. Part A: Hydrogel Development, Characterization and Coating", Carbohydrate Polymers 152:129-39. Collagen is the main structural protein in animal connective tissue and the most abundant protein in mammals. Starch is a carbohydrate consisting of a mixture of amylose and amylopectin. Hydrogels were developed with varying chemical composition (ratio of starch to gelatin applied) and different degrees of methacrylation of the applied gelatin phase. The hydrogels used exhibited no adverse effect on viability of the stem cells cultured on them. Moreover, initial cell adhesion did not differ significantly between them, while the strongest proliferation was observed on the hydrogel with the highest degree of cross-linking. On the least crosslinked and thus most flexible hydrogels, the highest degree of adipogenic differentiation was found, while osteogenic differentiation was the strongest on the most rigid, starch-blended hydrogels. Hydrogel coating with extracellular matrix compounds aggrecan or fibronectin prior to cell seeding exhibited no significant effects. Thus, gelatin-based hydrogels can be optimized regarding maximum promotion of either adipogenic or osteogenic stem cell differentiation in vitro, which makes them promising candidates for in vivo evaluation in clinical studies aiming at either soft or hard tissue regeneration.

A joint action of ssDNA aptamers and electrochemistry is a key element in developing successful biosensing platforms, since aptamers are capable of binding various targets with high specificity, and electrochemistry is one of the most sensitive techniques for on-site detections. A continuous search for improved immobilization and sensing strategies of aptamers on transducer surfaces resulted in the strategy presented in this article. The strategy is based on the covalent attachment of gold nanoparticles on the surface of glassy carbon electrodes through sulfhydryl-terminated monolayer, acting as a glue to connect AuNPs on the electrode. The covalently attached gold nanoparticles modified glassy carbon electrodes have been applied for the efficient immobilization of thiolated ssDNA probes, with a surface coverage of about 8.54 × 10 13 molecules cm −2 which was 7-fold higher than that on the electrochemically deposited gold nanoparticles. Consequently, improved sensitivity, good reproducibility and stability are achieved for electrochemical aptasensor. Combined with the high affinity and specificity of an aptamer, a simple, novel, rapid, sensitive and label-free electrochemical aptasensor was successfully fabricated for ofloxacin (OFL) detection. The linear dynamic range of the sensor varies between 5 × 10 −8 to 2 × 10 −5 M OFL with a detection limit of 1 × 10 −9 M OFL. A potential application in environmental monitoring was demonstrated by using this sensing strategy for the determination of OFL in (experimentally spiked) real samples such as tap water and effluent of sewage treatment plant. The proposed nanoaptasensor combines the advantages of the covalent attachment of neatly arranged AuNPs (enlarged active surface area and strengthened electrochemical signal) and the elimination of labels for the amplified detection of OFL, with the covalent attachment of highly specific aptamers to the surface of the modified electrode.

Recently, poly(2-oxazoline)s have regained significant interest and research has especially been focusing on biomedical applications. As non-woven nanofibrous mats show appealing features in this respect, the potential and limitations of electrospinning aqueous solutions of poly(2-ethyl-2-oxazoline) (PEtOx), the only poly(2-oxazoline) produced on industrial scale (i.e. Aquazol) so far, was evaluated. The polymer molecular weight appeared to be the dominant factor defining the optimal concentration range for successful nanofiber production. The molar mass distribution, i.e. the dispersity (D), is relevant as well. However, it is not a limiting factor as defined PEtOx (D < 1.2) could be electrospun without major adaptations to the electrospinning procedure that was optimized for the commercial grades of Aquazol with D of 3-4. By varying the PEtOx molecular weight and concentration, a broad range of fiber diameters can be targeted. Furthermore, we demonstrated the transferability of the PEtOx electrospinning parameters and the reproducibility of the resulting fiber diameters by repeating the experiments on an independent mononozzle electrospinning device, by a different operator. In order to fulfil all prerequisites for industrialization, we also demonstrated the feasibility for upscaling the PEtOx nanofiber production process using a pilot scale multinozzle electrospinning set-up. (C) 2016 Elsevier Ltd. All rights reserved.

Superabsorbent polymers (SAPs) have already found their way in many applications. Some of these polymers undergo major characteristic changes by small environmental variations which makes them interesting for self-healing of cracks in concrete. In the present work, polymer networks composed of dimethylaminoethyl methacrylate and N,N′-methylenebisacrylamide have been synthesized. Moisture uptake capacities up to 45% were measured at a relative humidity of 95%. They showed a desired pH-responsive swelling behavior with no degree of degradation. A small significant mortar strength reduction is found with addition up to 1 m% compared to the cement mass. All results were compared to commercially available SAPs.

The paper presents the synthesis, the physico-chemical and the biological properties of novel hybrid materials prepared from photo-crosslinked gelatin/alginate-based hydrogels and silica particles exhibiting potential for the regeneration of bone tissue. Both alginate and gelatin were functionalized with methacrylate and methacrylamide moieties, respectively to render them photo-crosslinkable. Submicron silica particles of two sizes were dispersed within three types of polymeric sols including alginate, gelatin, and gelatin/alginate blends, which were subsequently photo-crosslinked. The swelling ratio, the gel fraction and the mechanical properties of the hybrid materials developed were examined and compared to these determined for reference hydrogel matrices. The in vitro cell culture studies have shown that the prepared materials exhibited biocompatibility as they supported both MEFs and MG-63 mitochondrial activity. Finally, the in vitro experiments performed under simulated body fluid conditions have revealed that due to inclusion of silica particles into the biopolymeric hydrogel matrices the mineralization was successfully induced. ispartof: CARBOHYDRATE POLYMERS vol:157 pages:1714-1722 ispartof: location:England status: published

Corneal blindness is the fourth leading cause of visual impairment. Of specific interest is blindness due to a dysfunctional corneal endothelium which can only be treated by transplanting healthy tissue from a deceased donor. Unfortunately, corneal supply does not meet the demand with only one donor for every 70 patients. Therefore, there is a huge interest in tissue engineering of grafts consisting of an ultra-thin scaffold seeded with cultured endothelial cells. The present research describes the fabrication of such artificial Descemet membranes based on the combination of a biodegradable amorphous polyester (poly (d,l-lactic acid)) and crosslinkable gelatins. Four different crosslinkable gelatin derivatives are compared in terms of processing, membrane quality, and function, as well as biological performance in the presence of corneal endothelial cells. The membranes are fabricated through multi-step spincoating, including a sacrificial layer to allow for straightforward membrane detachment after production. As a consequence, ultrathin (90%), semi-permeable membranes could be obtained with high biological potential. The membranes supported the characteristic morphology and correct phenotype of corneal endothelial cells while exhibiting similar proliferation rates as the positive control. As a consequence, the proposed membranes prove to be a promising synthetic alternative to donor tissue.

The increasing number of mastectomies results in a greater demand for breast reconstruction characterized by simplicity and a low complication profile. Reconstructive surgeons are investigating tissue engineering (TE) strategies to overcome the current surgical drawbacks. 3D bioprinting is the rising technique for the fabrication of large tissue constructs which provides a potential solution for unmet clinical needs in breast reconstruction building on decades of experience in autologous fat grafting, adipose-derived mesenchymal stem cell (ASC) biology and TE. A scaffold was bioprinted using encapsulated ASC spheroids in methacrylated gelatin ink (GelMA). Uniform ASC spheroids with an ideal geometry and diameter for bioprinting were formed, using a high-throughput non-adhesive agarose microwell system. ASC spheroids in adipogenic differentiation medium (ADM) were evaluated through live/dead staining, histology (HE, Oil Red O), TEM and RT-qPCR. Viable spheroids were obtained for up to 14 days post-printing and showed multilocular microvacuoles and successful differentiation toward mature adipocytes shown by gene expression analysis. Moreover, spheroids were able to assemble at random in GelMA, creating a macrotissue. Combining the advantage of microtissues to self-assemble and the controlled organization by bioprinting technologies, these ASC spheroids can be useful as building blocks for the engineering of soft tissue implants.

We investigate the possibilities to realize light extraction from single crystal diamond (SCD) nanopillars. This was achieved by dedicated 519 nm laser-induced spin-state initiation of negatively charged nitrogen vacancies (NV−). We focus on the naturally-generated by chemical vapor deposition (CVD) growth of NV−. Applied diamond was neither implanted with 14N+, nor was the CVD synthesized SCD annealed. To investigate the possibility of light extraction by the utilization of NV−’s bright photoluminescence at room temperature and ambient conditions with the waveguiding effect, we have performed a top-down nanofabrication of SCD by electron beam lithography (EBL) and dry inductively-coupled plasma/reactive ion etching (ICP-RIE) to generate light focusing nanopillars. In addition, we have fluorinated the diamond’s surface by dedicated 0 V SF6 ICP plasma. Light extraction and spin manipulations were performed with photoluminescence (PL) spectroscopy and optically detected magnetic resonance (ODMR) at room temperature. We have observed a remarkable effect based on the selective 0 V SF6 plasma etching and surprisingly, in contrast to literature findings, deactivation of NV− centers. We discuss the possible deactivation mechanism in detail.

Current soft tissue repair techniques for women with breast cancer remain associated with several drawbacks including surgical complications and a high resorption rate for lipofilling techniques. Hence, the need to develop improved adipose tissue reconstruction strategies. Additive manufacturing can be a promising tool towards the development of patient-specific scaffolds which are able to support adipose tissue engineering. In the present work, scaffolds composed of both methacrylamide-modified gelatin (Gel-MA) and methacrylated kappa-carrageenan (Car-MA), i.e. hydrogel blends, were developed using extrusion-based 3D printing in order to establish a close resemblance to the native extracellular matrix. The hydrogel blends were benchmarked to scaffolds constituting of only Gel-MA. Our results indicate that both types of scaffolds remain stable over time (21 days), are able to absorb large amounts of water and exhibit mechanical properties comparable to those of native breast tissue (2 kPa). Furthermore, a similar cell viability (> 90%) and proliferation rate after 14 days was obtained for adipose tissue-derived stem cells (ASCs) upon seeding onto both types of scaffolds. Additionally, the ASCs were able to differentiate into the adipogenic lineage on the hydrogel blend scaffolds, although their differentiation potential was lower compared to that of ASCs seeded onto the Gel-MA scaffolds. (C) 2019 Elsevier B.V. All rights reserved.

Adipose tissue engineering aims to provide solutions to patients who require tissue reconstruction following mastectomies or other soft tissue trauma. Mesenchymal stromal cells (MSCs) robustly differentiate into the adipogenic lineage and are attractive candidates for adipose tissue engineering. This work investigates whether pore size modulates adipogenic differentiation of MSCs toward identifying optimal scaffold pore size and whether pore size modulates spatial infiltration of adipogenically differentiated cells. To assess this, extrusion-based 3D printing is used to fabricate photo-crosslinkable gelatin-based scaffolds with pore sizes in the range of 200-600 mu m. The adipogenic differentiation of MSCs seeded onto these scaffolds is evaluated and robust lipid droplet formation is observed across all scaffold groups as early as after day 6 of culture. Expression of adipogenic genes on scaffolds increases significantly over time, compared to TCP controls. Furthermore, it is found that the spatial distribution of cells is dependent on the scaffold pore size, with larger pores leading to a more uniform spatial distribution of adipogenically differentiated cells. Overall, these data provide first insights into the role of scaffold pore size on MSC-based adipogenic differentiation and contribute toward the rational design of biomaterials for adipose tissue engineering in 3D volumetric spaces.

Cell encapsulation in confining 3D hydrogels typically prevents encapsulated cells from spreading and establishing cell-cell contacts. Interactions with neighboring cells or with the extracellular matrix (ECM) influence the paracrine activity of mesenchymal stromal cells (MSCs), but how these interactions are regulated by structural properties of biomaterial scaffolds remains insufficiently explored. Here, we describe the use of extrusion-based 3D printing to fabricate acellular, gelatin-based scaffolds with programmed strut spacings of 400 (small), 500 (medium), and 600 μm (large). These scaffolds showed similar effective Young's moduli in the range of 2-5 kPa, and varied based on average pore size which ranged from ∼200 μm (small pore: SP) through ∼302 μm (medium pore: MP) to ∼382 μm (large pore: LP). When seeded with MSCs, pore size guided cell distribution on the scaffolds, with smaller pores preventing cell infiltration, medium ones causing cells to aggregate in between struts, and large ones causing cells to flow through after attachment on the struts. These changes in cell distribution regulated cell-cell and cell-matrix interactions at the gene level, as assessed by pathway focused PCR arrays. Medium pore size scaffolds stimulated the highest paracrine secretion of a panel of angiogenic cytokines. This enhancement of paracrine activity substantially improved endothelial cell migration in a chemotaxis assay, increased single cell migration kinetics such as velocity, and stimulated the formation of robust tubular structures. Together, these findings not only provide new insights on cellular interactions in scaffold environments but also demonstrate how 3D biomaterial design can instruct and enhance the regenerative paracrine activities of MSCs.

The z-scan technique has become a standard method to measure 2-photon absorption (2PA) properties of materials used for 2-photon applications. Here we present a completely automated, easily tunable z;-scan setup for spectral scanning. An algorithm collecting the required laser beam parameters allows to reliably determine the optimal working window of newly synthesized 2PA photoinitiators (PI) used for two-photon polymerization (2PP) in a wide spectral range. A complete spectrum (3 measurements per wavelength in 10 nm steps) can be obtained within an hour. Matching the wavelength used for 2PP to the maximum 2PA significantly increased the 2PP performance of the system. Published by The Optical Society under the terms of the Creative Commons Attribution 4.0 License.

Gelatin is frequently used in various biomedical applications. However, gelatin is generally extracted from an animal source, which can result in issues with reproducibility as well as pathogen transmittance. Therefore, we have investigated the potential of a recombinant peptide based on collagen I (RCPhC1) for tissue engineering applications and more specifically for adipose tissue regeneration. In the current paper, RCPhC1 was functionalized with photo-crosslinkable methacrylamide moieties to enable subsequent UV-induced crosslinking in the presence of a photo-initiator. The resulting biomaterial (RCPhC1-MA) was characterized by evaluating the crosslinking behaviour, the mechanical properties, the gel fraction, the swelling properties and the biocompatibility. The obtained results were compared with the data obtained for methacrylamide-modified gelatin (Gel-MA). The results indicated that the properties of RCPhC1-MA networks are comparable to those of animal-derived Gel-MA. RCPhC1-MA is thus an attractive synthetic alternative for animal-derived Gel-MA and is envisioned to be applicable for a wide range of tissue engineering purposes.

Superabsorbent polymers (SAPs) can be added to a concrete mixture to provide internal curing and reduce the risk for early-age shrinkage cracking. Hence, they can help to increase the overall durability of concrete structures. The type, swelling characteristics, kinetics of water release, amount and particle size of the SAPs will dictate their effectiveness for this purpose. In this paper, SAPs with different cross-linking degrees, particle sizes and amount of solubles are investigated. By varying these parameters, insight can be gained on the influence of each of these parameters on SAP properties such as the swelling capacity. In a next step, the SAPs can be implemented in mortar to assess their influence on mortar properties like workability, compressive strength or hydration kinetics. Based on these results, the &lsquo, ideal&rsquo, SAP with tunable properties for a specific concrete application can be selected. For this purpose, an anionic SAP was synthesized with varying amounts of cross-linker and ground to particle sizes with d50 varying between 10 and 100 &micro, m. The swelling capacity in demineralised water of 40 &micro, m SAP particles increased with a decreasing degree of cross-linker from 66 g/g SAP with 1 mol% cross-linker to 270 g/g SAP in case of 0.15 mol% cross-linker, and was about three to four times larger than the swelling capacity in the prepared cement filtrate. The SAPs were tested for their effect on mortar workability, cement hydration kinetics and mechanical properties of the hardened mortar. With proper compensation for the absorbed water by the SAPs, the mortar workability was not negatively affected and the reduction in flow over the first two hours remained limited. The SAPs with the lowest swelling capacity, resulting in the smallest total amount of macro pores formed, showed the smallest negative effect on mortar compressive strength (a reduction of 23% compared to the reference after 28 days for an addition of 0.5 m% SAP) and a negligible effect on cement hydration. The difference in strength with the reference decreased as a function of mortar age. When using SAPs with particle sizes in the range of 10&ndash, 100 &micro, m, no significant differences between the studied particle sizes were found concerning the mortar properties. With the ease of upscaling in mind, the need to purify the SAPs and to remove the non-cross-linked soluble fraction was further investigated. It was shown that the solubles had no effect on the mortar properties, except for increasing the setting time with almost 100%.

Hydrogels are interesting as wound dressing for burn wounds to maintain a moist environment. Especially gelatin and alginate based wound dressings show strong potential. Both polymers are modified by introducing photocrosslinkable functionalities and combined to hydrogel films (gel-MA/alg-MA). In one protocol gel-MA films are incubated in alg-MA solutions and crosslinked afterward into double networks. Another protocol involves blending both and subsequent photocrosslinking. The introduction of alginate into the gelatin matrix results in phase separation with polysaccharide microdomains in a protein matrix. Addition of alg(-MA) to gel-MA leads to an increased swelling compared to 100% gelatin and similar to the commercial Aquacel Ag dressing. In vitro tests show better cell adhesion for films which have a lower alginate content and also have superior mechanical properties. The hydrogel dressings exhibit good biocompatibility with adaptable cell attachment properties. An adequate gelatin-alginate ratio should allow application of the materials as wound dressings for several days without tissue ingrowth. ispartof: MACROMOLECULAR BIOSCIENCE vol:19 issue:8 ispartof: location:Germany status: published

Photodynamic therapy (PDT) involves a photosensitizing agent activated with light to induce cell death. Two-photon excited PDT (TPE-PDT) offers numerous benefits compared to traditional one-photon induced PDT, including an increased penetration depth and precision. However, the in vitro profiling and comparison of two-photon photosensitizers (PS) are still troublesome. Herein, we report the development of an in vitro screening platform of TPE-PS using a 3D osteosarcoma cell culture. The platform was tested using three different two-photon (2P) active compounds - a 2P sensitizer P2CK, a fluorescent dye Eosin Y, and a porphyrin derivative (TPP). Their 2P absorption cross-sections (σ2PA) were characterised using a fully automated z-scan setup. TPP exhibited a remarkably high σ2PA at 720 nm (8865 GM) and P2CK presented a high absorption at 850 nm (405 GM), while Eosin Y had the lowest 2P absorption at the studied wavelengths (

Varying physico-chemical properties of synthetic hydrogels and introducing additives can induce a cell interactive response of hydrogels. Hydrogels were developed based on acrylate-endcapped urethane-based poly(ethylene glycol) precursors with varying backbone molecular weight (2000–8000 g/mol), in combination with the nanoclay Laponite to explore effects on swelling, mechanical and in vitro biological properties. The combined effect of molecular weight and Laponite concentration enables the development of hybrid materials useful for different biomedical applications. Gel fractions approximating 100% along with tunable swelling (4–11 g/g polymer) and mechanical properties (Young's Modulus 0.1–0.6 MPa) are obtained. All materials are non-cytotoxic and AUPs without Laponite are non cell-interative rendering them suitable for non-adherent biomedical applications. Hydrogels composed of Laponite (0.5 or 1 wt%) and PEG backbone molecular weight of 2000 g/mol promote cell proliferation useful to function as synthetic dermal matrices or scaffolds for tissue engineering applications.

Gelatin-modified poly(ethylene terephthalate) (PET) surfaces have been previously realized via an intermediate dopamine coating procedure that resulted in surfaces with superior haemocompatibility compared to unfunctionalized PET. The present study addresses the biocompatibility assessment of these coated PET surfaces. In this context, the stability of the gelatin coating upon exposure to physiological conditions and its cell-interactive properties were investigated. The proposed gelatin–dopamine-PET surfaces showed an increased protein coating stability up to 24 days and promoted the attachment and spreading of both endothelial cells (ECs) and smooth muscle cells (SMCs). In parallel, physisorbed gelatin coatings exhibited similar cell-interactive properties, albeit temporarily, as the coating delaminated within 1 week after cell seeding. Furthermore, no or only minimal immunogenic or inflammatory responses were observed during in vitro cytotoxicity and endotoxicity assessment for all gelatin-modified PET surfaces evaluated. Overall, the combined enhanced biocompatibility reported herein together with the previously proven haemocompatibility show the potential of the gelatin–dopamine-PET surfaces to function as vascular graft candidates.

In hybrid bioprinting of cartilage tissue constructs, spheroids are used as cellular building blocks and combined with biomaterials for dispensing. However, biomaterial intrinsic cues can deeply affect cell fate and to date, the influence of hydrogel encapsulation on spheroid viability and phenotype has received limited attention. This study assesses this need and unravels 1) how the phenotype of spheroid-laden constructs can be tuned through adjusting the hydrogel physico-chemical properties and 2) if the spheroid maturation stage prior to encapsulation is a determining factor for the construct phenotype. Articular chondrocyte spheroids with a cartilage specific extracellular matrix (ECM) are generated and different maturation stages, early-, mid-, and late-stage (3, 7, and 14 days, respectively), are harvested and encapsulated in 10, 15, or 20 w/v% methacrylamide-modified gelatin (gelMA) for 14 days. The encapsulation of immature spheroids do not lead to a cartilage-like ECM production but when more mature mid- or late-stage spheroids are combined with a certain concentration of gelMA, a fibrocartilage-like as well as a hyaline cartilage-like phenotype can be induced. As a proof of concept, late-stage spheroids are bioprinted using a 10 w/v% gelMA-Irgacure 2959 solution with the aim to test the processing potential of the spheroid-laden bioink.

The present paper demonstrates the successful RAFT/MADIX polymerization of N-vinylcaprolactam at ambient temperature in water–ethanol mixtures. It was observed that the monomer conversion increased with increasing v% of water present in the solvent due to an improved polymer solvation. Simultaneously the monomer hydrolysis also increased with increasing water content and a 1 : 1 ratio of water and ethanol was found as optimum regarding both polymerization rate and insignificant hydrolysis. In future, the application of these low toxicity solvent mixtures of ethanol and water can be applied to enable new avenues towards bioconjugation.

In the present work, a photopolymerized urethane-based poly(ethylene glycol) hydrogel is applied as a porous scaffold material using indirect solid freeform fabrication (SFF). This approach combines the benefits of SFF with a large freedom in material selection and applicable concentration ranges. A sacrificial 3D poly(ε-caprolactone) structure is generated using fused deposition modeling and used as template to produce hydrogel scaffolds. By changing the template plotting parameters, the scaffold channel sizes vary from 280 to 360 μm, and the strut diameters from 340 to 400 μm. This enables the production of scaffolds with tunable mechanical properties, characterized by an average hardness ranging from 9 to 43 N and from 1 to 6 N for dry and hydrated scaffolds, respectively. Experiments using mouse calvaria preosteoblasts indicate that a gelatin methacrylamide coating of the scaffolds results in an increased cell adhesion and proliferation with improved cell morphology.

To date, the potential of several types of polymeric materials as healing agents for self-healing of concrete has already been investigated. Generally, for self-healing concrete with encapsulated polymeric healing agents, the curing mechanism is triggered upon contact with moisture/air or upon reaction with a second component provided by additional capsules. The present work explores the use of in-situ curable hydrogels formed as a result of the elevated pH of the cementitious matrix, via a Michael-type addition reaction, as potential healing/sealing materials for concrete applications. For this purpose, a variety of acrylate-endcapped urethane-based precursors were synthesized and combined with a thiol-based cross-linker. Various properties including the viscosity, the curing time, the swelling capacity and the cross-linking efficiency have been evaluated. The potential of the developed materials to seal concrete cracks was assessed through manual injection. The results indicate that the cross-linking reaction can readily occur in-situ due to the alkaline environment of the cementitious matrix and that the hydrogels exhibit favorable sealing properties. Keywords: Self-healing, Concrete, Hydrogel precursor, Michael-type addition reaction, In-situ curable hydrogels

This work reveals how the physicochemical properties of Pluronic block copolymers influence significantly their interactions with cancer cells, whether in monolayer or spheroid cultures, and how different clinical applications can be foreseen. Two-dimensional (2D) and three-dimensional (3D) cell culture models were used to investigate the interactions of Pluronic carriers with different PEO block length and aggregation state (unimers versus cross-linked micelles) in HeLa and U87 cancer cells. Stabilized micelles of Pluronic P94 or F127 were obtained by polymerization of a crosslinking agent in the micelles hydrophobic core. Nanocarriers were functionalized with a fluorescent probe for visualization, and with a chelator for radiolabeling with Indium-111 and gamma-quantification. The 2D cell models revealed that the internalization pathways and ultimate cellular localization of the Pluronic nanocarriers depended largely on both the PEO block size and aggregation state of the copolymers. The smaller P94 unimers with an average radius of 2.1nm and the shortest PEO block mass (1100gmol(-1)) displayed the highest cellular uptake and retention. 3D tumor spheroids were used to assess the penetration capacity and toxicity potential of the nanocarriers. Results showed that cross-linked F127 micelles were more efficiently delivered across the tumor spheroids, and the penetration depth depends mostly on the transcellular transport of the carriers. The Pluronic P94-based carriers with the shortest PEO block length induced spheroid toxicity, which was significantly influenced by the spheroid cellular type.

Malodorous wounds have a detrimental effect on the patient's well‐being. A dressing combining the properties of hydrogels and activated carbon (AC) would be beneficial for the treatment of these wounds, controlling wound exudate while adsorbing malodor‐causing compounds. The present work involves the use of acrylate‐endcapped, urethane‐based precursors (AUPs) and methacrylated alginate (AlgMOD). AUPs are synthesized with a varying poly(ethylene glycol) backbone molar mass (2–20 kg mol−1) to tune mechanical and swelling properties, whereas methacrylated alginate, known for its hemostatic properties, enables chemical cross‐linking. Blends of AUP and AlgMOD with AC are processed into hydrogel sheets and electrospun membranes. The results indicate tunable mechanical (Young's moduli 0.03–0.63 MPa) and swelling properties (2.2–34.9 gwater ghydrogel−1) along with high gel fractions (>85%). The sheets are compared with commercial odor‐adsorbing dressings (Carbonet and Carboflex), enabling benchmarking. AUP sheets (8 and 10 kg mol−1) containing 0.5% w/w AC show strong adsorption (>90% after 24 h) of crystal violet. The obtained (core–shell AlgMOD/AUP) fibers are visualized using scanning and transmission electron microscopy. Indirect cell tests reveal the developed materials to be biocompatible. In conclusion, a hydrogel‐based odor‐adsorbing wound dressing is successfully synthesized and holds promise for malodorous wound healing.

One of the most promising fields for shape-memory polymers is the biomedical field. Shape-memory polymers that can be triggered by various (physiological) conditions such as temperature and moisture have been reported, as well as remotely triggerable shape-memory polymers that make use of electromagnetic fields, ultrasound, etc. These polymers have shown great promise in in vitro studies as well as in early in vivo studies. Their biocompatibility, and in some cases biodegradability, renders them excellent candidates for minimal invasive surgery and for the design of triggerable biomedical devices. The current review provides a nonexhaustive overview of recent developments realized throughout the last decade in the field of shape-memory polymers serving specific biomedical applications while considering relevant triggers and biocompatible chemistries.

There exists a clear clinical need for adipose tissue reconstruction strategies to repair soft tissue defects which outperform the currently available approaches. In this respect, additive manufacturing has shown to be a promising alternative for the development of larger constructs able to support adipose tissue engineering. In the present work, a thiol-ene photo-click crosslinkable gelatin hydrogel was developed which allowed extrusion-based additive manufacturing into porous scaffolds. To this end, norbornene-functionalized gelatin (Gel-NB) was combined with thiolated gelatin (Gel-SH). The application of a macromolecular gelatin-based thiolated crosslinker holds several advantages over conventional crosslinkers including cell-interactivity, less chance at phase separation between scaffold material and crosslinker and the formation of a more homogeneous network. Throughout the paper, these photo-click scaffolds were benchmarked to the conventional methacrylamide-modified gelatin (Gel-MA). The results indicated that stable scaffolds could be realized which were further characterized physico-chemically by performing swelling, mechanical and in vitro biodegradability assays. Furthermore, the seeded adipose tissue-derived stem cells (ASCs) remained viable (>90%) up to 14 days and were able to proliferate. In addition, the cells could be differentiated into the adipogenic lineage on the photo-click crosslinked scaffolds, thereby performing better than the cells supported by the frequently reported Gel-MA scaffolds. As a result, the developed photo-click crosslinked scaffolds can be considered a promising candidate towards adipose tissue engineering and a valuable alternative for the omnipresent Gel-MA. Statement of Significance The field of adipose tissue engineering has emerged as a promising strategy to repair soft tissue defects. Herein, Gel-NB/Gel-SH gelatin-based hydrogel scaffolds were produced using extrusion-based additive manufacturing. Using a cell-interactive, thiolated gelatin crosslinker, a homogeneous network was formed and the risk of phase separation between norbornene-modified gelatin and macromolecular crosslinkers was reduced. UV-induced crosslinking of these materials is based on step growth polymerization which requires less free radicals to enable polymerization. Our results demonstrated the potential of the developed scaffolds, due to their favourable physico-chemical characteristics as well as their adipogenic differentiation potential when benchmarked to Gel-MA scaffolds. Hence, the hydrogels could be of great interest towards future development of adipose tissue constructs and tissue engineering in general.

The current review provides an overview of different types of superabsorbent polymers (SAPs) together with appropriate strategies elaborated to enable their synthesis. The main focus will be on polysaccharide-based, semi-synthetic and 'smart' SAPs along with their derivatives. SAPs have already shown their use in a plethora of applications including diapers, the biomedical field, agriculture, etc. The different polymer classification possibilities are discussed, as well as the classification of the constituting building blocks. The main part of SAPs still has a synthetic origin. However, as they are often not biocompatible, biodegradable or renewable, natural SAPs based on polysaccharides have gained increasing interest. Due to the low solubility of synthetic polymers, purification problems or the need for organic solvents, a trend has emerged towards combining polysaccharides with synthetic monomers to create semi-synthetic, hybrid SAPs for specialized applications with fine-tuned properties including wound dressings, fertilizers or self-healing concrete. These specialized, semi-synthetic SAPs offer strong potential for a series of applications in the future. However, future research in this respect is still needed to optimize homogeneity and to increase gel fractions. A final part of this review includes 'smart' SAPs such as SAPs with a T-, electro- and pH-sensitivity. These 'smart' SAPs are especially becoming useful for certain biomedical applications such as drug release for which an in vivo location can be targeted. The use of 'smart', semi-synthetic SAPs with fine-tuned characteristics combining the best characteristics of both synthetic and natural SAPs, offer the greatest potential for the future.

Over the recent decades gelatin has proven to be very suitable as an extracellular matrix mimic for biofabrication and tissue engineering applications. However, gelatin is prone to dissolution at typical cell culture conditions and is therefore often chemically modified to introduce (photo-)crosslinkable functionalities. These modifications allow to tune the material properties of gelatin, making it suitable for a wide range of biofabrication techniques both as a bioink and as a biomaterial ink (component). The present review provides a non-exhaustive overview of the different reported gelatin modification strategies to yield crosslinkable materials that can be used to form hydrogels suitable for biofabrication applications. The different crosslinking chemistries are discussed and classified according to their mechanism including chain-growth and step-growth polymerization. The step-growth polymerization mechanisms are further classified based on the specific chemistry including different (photo-)click chemistries and reversible systems. The benefits and drawbacks of each chemistry are also briefly discussed. Furthermore, focus is placed on different biofabrication strategies using either inkjet, deposition or light-based additive manufacturing techniques, and the applications of the obtained 3D constructs. STATEMENT OF SIGNIFICANCE: Gelatin and more specifically gelatin-methacryloyl has emerged to become one of the gold standard materials as an extracellular matrix mimic in the field of biofabrication. However, also other modification strategies have been elaborated to take advantage of a plethora of crosslinking chemistries. Therefore, a review paper focusing on the different modification strategies and processing of gelatin is presented. Particular attention is paid to the underlying chemistry along with the benefits and drawbacks of each type of crosslinking chemistry. The different strategies were classified based on their basic crosslinking mechanism including chain- or step-growth polymerization. Within the step-growth classification, a further distinction is made between click chemistries as well as other strategies. The influence of these modifications on the physical gelation and processing conditions including mechanical properties is presented. Additionally, substantial attention is put to the applied photoinitiators and the different biofabrication technologies including inkjet, deposition or light-based technologies.

The use of graphene in optical and photonic applications has gained much attention in recent years. To maximize the exploitation of graphene's extraordinary optical properties, precise control over its Fermi level (e.g. by means of chemical doping) will be of vital importance. In this work, we show the usage of a versatile p-doping strategy based on the incorporation of bis(trifluoromethanesulfonyl)amide (TFSA), functioning as an active p-dopant molecule, into a poly(2,2,3,3,4,4,5,5-octafluoropentyl methacrylate) (POFPMA) polymer matrix. The TFSA/POFPMA dopant can be utilized both onto large size graphene regions via spin coating and on small predefined spatial zones of micrometer dimension by localized inkjet printing. Whereas pure TFSA suffers from a clustered layer deposition combined with environmental instability, the application of the POFPMA polymer matrix yields doping layers revealing superior properties counteracting the existing shortcomings of pure TFSA. A first key finding relates to the optical quality of the dopant layer. We obtain a layer with an extremely low surface roughness (0.4-0.8 nm/25 μm 2) while exhibiting very high transparency (absorbance

The placenta is a transient organ, essential for development and survival of the unborn fetus. It interfaces the body of the pregnant woman with the unborn child and secures transport of endogenous and exogenous substances. Maternal and fetal blood are thereby separated at any time, by the so-called placental barrier. Current in vitro approaches fail to model this multifaceted structure, therefore research in the field of placental biology is particularly challenging. The present study aimed at establishing a novel model, simulating placental transport and its implications on development, in a versatile but reproducible way. The basal membrane was replicated using a gelatin-based material, closely mimicking the composition and properties of the natural extracellular matrix. The microstructure was produced by using a high-resolution 3D printing method – the two-photon polymerization (2PP). In order to structure gelatin by 2PP, its primary amines and carboxylic acids are modified with methacrylamides and methacrylates (GelMOD-AEMA), respectively. High-resolution structures in the range of a few micrometers were produced within the intersection of a customized microfluidic device, separating the x-shaped chamber into two isolated cell culture compartments. Human umbilical-vein endothelial cells (HUVEC) seeded on one side of this membrane simulate the fetal compartment while human choriocarcinoma cells, isolated from placental tissue (BeWo B30) mimic the maternal syncytium. This barrier model in combination with native flow profiles can be used to mimic the microenvironment of the placenta, investigating different pharmaceutical, clinical and biological scenarios. As proof-of-principle, this bioengineered placental barrier was used for the investigation of transcellular transport processes. While high molecular weight substances did not permeate, smaller molecules in the size of glucose were able to diffuse through the barrier in a time-depended manner. We envision to apply this bioengineered placental barrier for pathophysiological research, where altered nutrient transport is associated with health risks for the fetus.

Hypothesis The complete removal of remaining polymer debris after stripping of optical fiber cables is essential for high precision connection between two fibers. It can be anticipated that electrospun porous membranes as cleaning wipes are able to trap and retain polymer debris within their pores. Impregnation of an oil-in-water emulsion as cleaning agent lowers the interfacial tension between debris and the optical fiber thereby enabling the straightforward removal of polymer debris from the optical fiber. Experiments Electrospun membranes of poly(ethylene terephthalate) (PET) and cellulose acetate (CA) were obtained with fiber diameters of 0.430 μm and 2 μm respectively. The oil-in-water emulsion was formulated with 10 wt% medium chain triglyceride (MCT) and 10 wt% Tween 80 surfactant in an aqueous phosphate buffer solution. Findings In a scoring range from 0 to 5 for which the score 0 indicated superior cleaning and the score 5 referred to the least efficient cleaning, the electrospun fiber mats (without emulsion) scored within the range of 2–4 while emulsion impregnated electrospun fiber mats revealed the best score of 0. A drastic improvement was thus clearly evident from the obtained results when the cleaning emulsion was applied. The materials developed herein thus represent a new class of soft cleaning agents for optical fibers.

The joining of materials is essential to many industrial applications used today. However, it still lacks a reliable and true single step method to join different types of materials including polymers. Laser welding was primarily employed for metals until some decades ago, but with the rise of high power solid state lasers, applications have emerged in the polymer field. With the recent addition of fiber lasers, true clear to clear welding, joining two of the same transparent polymer layers, has become feasible at a different wavelength range, which benefits the sealing of microfluidic devices. A number of research efforts were made at performing welds of thermoplastics at this wavelength range, however without attempts at offering elaborate explanation of the observations. In our work, a laser welding system using a Thulium fiber laser at 1940 nm was used to join a variety of thermoplasts, without the use of additives or prior processing. By optically and chemically characterizing the materials, a basis was established that links intrinsic material properties to observed welding performance, as determined by mechanical shear tests on the welded materials. We found that four of the ten considered thermoplastic polymers lend themselves to sufficiently strong bonding to allow the creation of leak-proof microfluidic devices by use of laser welding at this wavelength.