Fibril-forming tropocollagens (TCs) play an essential role in tissue biomechanics. They are ubiquitous in mammals and other animal tissues, where they provide passive mechanical functions. While molecular dynamics simulations have targeted the mechanics of individual TCs, experimental data on their tensile mechanical properties remain scarce. As a consequence, the link between the unique triple-helix structure of the collagen molecule and macro-mechanical properties of collagenous tissues is not well understood. To close this gap, we have investigated isolated TCs grafted on the tip of atomic force microscopy (AFM) probes as well as adsorbed TC films using a surface force apparatus (SFA). AFM force spectroscopy showed that an individual TC can be stretched without failing to a contour length of up to 900 nm─nearly three times its native length─over thousands of stretching cycles. The molecule was retracted from a strongly adhering mica surface by pulling on one of the α-chains, forcing the triple-helix to unravel. During this process, the α-chains slipped progressively, irreversibly, and almost entirely past each other before being caught by strong physical interactions between overlapping chain ends. SFA measurements showed that strong electrostatic interactions bind TC to mica and prevent TC aggregation, supporting the AFM results. These findings indicate that a controlled slippage mechanism underpins the exceptional toughness of TCs, collagen fibrils, and collagen-rich tissues such as tendons and skin.

Over the last years, stereolithography has developed to be one of the most promising fabrication techniques in tissue engineering. Posing the possibility of fabricating patient-specific, porous implants, it became especially attractive for scaffold fabrication for the treatment of critical sized bone defects. State-of-the-art photopolymer systems mostly consist of potentially cytotoxic compounds, such as (meth)acrylates, that furthermore show insufficient degradation and lead to acidic degradation products that could induce adverse tissue reactions. Herein, we introduced trifunctional monomers comprising cleavable silyl ether groups for thiol-ene photopolymerization to enlarge the material platform for printed bone grafts. Polymer networks comprising a high number of silyl ether moieties typically tend to be mechanically weak and exhibit low Tg values, especially when combined with thioether bonds, which are a direct result of polymerization via thiol-ene click reaction. To push thermomechanical properties to a level where they are sufficient for bone grafting (Tg > 37 °C), we introduced rigid bridged alicyclic structures in the form of norbornane-derived motifs into the silyl ether monomers, resulting in a norbornene-containing double bond monomer and a norbornane-derived thiol monomer. Together with noncleavable comonomers, we were able to demonstrate a substantial increase in Tg up to 62 °C, which is well above the values reported until now for similar thiol-ene networks. Furthermore, in this study, we demonstrated high photoreactivity for some of the monomers and also successfully performed proof-of-concept printing using a DLP setup. Besides excellent thermomechanical behavior, the mechanical strength of the silyl ether-based polymer network was shown to be outstanding. Cleavability of the silyl ethers was displayed with a quasi-linear degradation rate of 6.5% per month with moderate swelling. Additionally, the degradation product of the silyl ether-based network was isolated and shown to exhibit no relevant cytotoxicity to mouse fibroblast cells.

dMRI is a promising imaging technique for examining the human brain. Validation of dMRI is challenging, and specialized test samples, so-called brain phantoms, that mimic the tissue microstructure authentically, are needed. High-resolution 3D printing by means of 2-Photon Polymerization allows for the manufacturing of such novel brain phantoms. (e-mail: franziska.gantner@tuwien.ac.at). (c) 2025 The Author(s).

Photoinitiators (PIs) represent the key molecules within a photopolymerizable resin, due to their ability to generate the initiating species. However, the majority of state-of-the-art PIs comprise aromatic chromophores, known to produce cytotoxic photoproducts, whose migration out of the cured resin poses both environmental and human health threats. Herein, we present a set of multifunctional, aliphatic free radical photoinitiators based on the alpha-ketoester moiety, which exhibit low cytotoxicity even after irradiation. By systematically increasing the number of PI moieties, purely aliphatic molecules comprised of up to four radical-generating units have been synthesized. High miscibility in both organic and water-based formulations, combined with excellent photoreactivity and no discoloration upon irradiation with broadband (320-500 nm) and LED (385 nm) light sources, are demonstrated. The developed alpha-ketoester derivatives outperform the benchmark Norrish type II benzophenone/amine system and can be used for advanced applications, including UV-nanoimprint lithography as well as additive manufacturing technologies (DLP 3D printing).

In this study, we successfully created an implant to mimic natural bone by combining a load-bearing shell made of zirconia (cortical bone) with an osteoconductive filling made of hydroxyapatite (cancellous bone). Using additive manufacturing, both parts were produced separately followed by a sinter-joining process to form one hybrid final part. We first tested the sinter-joining process on a simple ring-in-ring design, creating a defined press-fit between the outer and inner ring. We also introduced sinter supports to ensure excellent alignment and manufactured biaxial bending plates to test the mechanical resistance. We found a significant increase in the maximal measured force from (72±53) N to (366±88) N for a 5 % and 10 % press-fit, respectively. Furthermore, we successfully manufactured a more complex bone implant with this sinter-joining method.

Photolabile hydrogels have gained tremendous interest for a wide range of applications in materials and life sciences. Usually, photodegradability is introduced via chromophores and labile bonds, making such materials intrinsically light sensitive. In recent years, disulfide bonds have emerged as an innovative alternative, as they can be selectively cleaved in the presence of (photo)generated radicals. However, such materials suffer from limited network stability and high swelling as a result of thiol-disulfide metathesis reactions. Herein, we present two strategies to counteract such phenomena by network stabilization either via physical or chemical incorporation of (un)modified gelatin macromers to norbornene-modified poly(vinyl alcohol) networks. Photolabile behavior was introduced by a simple disulfide-containing dithiol cross-linker. Tunable material properties were investigated by means of in situ photorheology, in vitro swelling, and degradation experiments. Finally, we demonstrate an innovative method for localized disulfide cleavage via two-photon micropatterning.

Biodegradable thermoplastic polyurethanes (TPUs) are promising materials for vascular grafts, due to their excellent mechanical properties and the possibility to incorporate degradable moieties. Especially degradability is important in the field of tissue engineering (TE) or regenerative medicine, because the synthetic scaffold should be replaced by human tissue after a certain time. We synthesized thermoplastic polythiourethanes (TPTUs) based on degradable chain extenders and tested their mechanical, thermal and degradation characteristics. As soft-block we used polytetrahydrofuran (pTHF) and as hard-block the aliphatic hexamethylenediisocyanate (HMDI) in combination with a variety of chain extenders. The focus was set on the boronic acid-based dithiol 2,2 '-(1,4-phenylene)-bis[4-mercaptan-1,3,2-dioxaborolane] (BDB). As dithiol-based reference 1,2-bis(2-mercaptoethoxy)ethane (BMEE) was used and bis(2-hydroxyethyl)-terephthalate (BHET) as well-known ester-based reference chain extender. By using BDB as degradable chain extender we could accelerate the degradation rate in terms of mass erosion at 37 and 90 degrees C compared to BHET-based TPUs. However, a strong increase in molecular weight was observed under degradation conditions. Further investigation by ATR-FTIR revealed a release of benzene-1,4-diboronic acid (BDBA) in the polymer. This leads to the formation of a hydroxy-terminated polyol, which then undergoes an intramolecular functional group metamorphosis with the thiourethane group to form a crosslinked polymer. BMEE-based TPTUs in contrast show excellent mechanical properties, even better than BHET-TPUs but a slightly lower mass erosion at 37 and 90 degrees C.

Interactions between tissue and material post-implantation significantly impact the long-term behavior of vascular prostheses. Autologous materials are preferred for replacing small-diameter blood vessels due to their superior healing properties compared to synthetic options. This study aimed to characterize the host response to autologous and various synthetic grafts in vitro and in vivo during the early healing phase, focusing on anastomotic regions and perivascular adipose tissue (PVAT). Immune cell activation by seeding human macrophages and neutrophils onto decellularized umbilical cord arteries (dUCAs), biodegradable thermoplastic polyether-urethane (TPU/TPUU), and expanded polytetrafluoroethylene (ePTFE) grafts was assessed in vitro. Autologous aortic grafts, TPU/TPUU, and ePTFE grafts were implanted in rats to evaluate cytokine expression in anastomotic regions at 24 h and 1 week, alongside protein and gene expression analyses of PVAT. Decellularized UCA grafts elicited less pro-inflammatory macrophage activation than ePTFE and TPU/TPUU in vitro. Autologous grafts exhibited no inflammatory response in anastomotic regions, while ePTFE displayed significantly higher cytokine and pro-inflammatory gene expression at 24 h after implantation. TPU/TPUU specimens showed a delayed response. PVAT analyses revealed significant inflammation in ePTFE implants, contrasting with limited pro-inflammatory activation in autologous and TPU/TPUU grafts. Significant differences in the upregulation of inflammatory cytokines and pro-inflammatory genes can be observed in the early postoperative healing phase. Therefore, new synthetic materials or therapeutic approaches targeting inadequate healing response at the early stage would be mandatory to overcome current graft performance limitations. In particular, the role of PVAT in vascular graft healing should be evaluated in detail.

The vision of using bone adhesives for adjunct surgical treatment of complicated fractures or facile reattachment of bone fragments is highly attractive, as compared to conventional techniques, it is expected to significantly reduce operation times and potentially avoid the need for revision surgeries. Nevertheless, no commercial adhesives, that combine biocompatibility, sufficient bonding strength, and time-efficient, implementable fixation protocols are available yet. Inspired by self-etching dental restoratives, we present the development of novel adhesive molecules, so-called primers, containing adhesion motifs for high binding affinity to bone and implants and co-polymerizable groups for incorporation into the adhesive matrix. By efficient design of this primer molecule with regards to spacer length and type and number of polymerizable groups, we were able to develop the first-known one-step in situ photocurable adhesive system, based on thiol-ene chemistry with a shear bond strength comparable to dental adhesives. Unprecedented shear bond strength on bone was determined with the optimized system, which surpasses the state-of-the-art thiol-ene adhesive reported in literature by more than 70%. Good in vitro biocompatibility of the novel primer was determined, and, remarkably, first ex vivo indentation tests on the calvariae of rats revealed exceptional adhesive performance with failure of the calvariae instead of the adhesive. Due to combining practicability and applicability, this adhesive system might pave the way towards the future of adjunct fracture treatment, with applications such as the fixation of comminuted fractures, small or thin bone fragments, or the additional fixation of implants.

Nonlinear (NL) absorption and refraction are crucial optical phenomena in the development and application of optical materials. The Z-scan technique, first proposed by Bahae, is widely used to accurately measure the coefficients of NL absorption and refraction. This review presents a comprehensive overview of the most established versions of the Z-scan technique, including the transmittance closed aperture (CA) and open aperture (OA) Z-scan, reflecting CA and OA Z-scan, eclipsing Z-scan, and white light Z-scan. In each version, different sources with varying spatial and temporal intensity distributions are usually utilized. Numerical and analytical calculation results are provided for each version considering both continuous wave (CW) and pulsed laser sources. Unlike conventional reviews, which often summarize previously published results, this review primarily focuses on reproducing the findings from the literature. The analytical results, which are typically derived under specific approximations, are compared with numerical calculations to highlight the limitations of analytically derived relations. Furthermore, the necessary criteria and conditions for applying each Z-scan version are discussed.

Polarity‐reversal catalysts (PRCs) for hydrogen‐atom transfer reactions have been known in radical chemistry for more than 60 years but are rarely described and utilized in the field of photopolymerization up to now. Herein, we present the use of thiols in a unique dual function as thiol‐ene click reagents and as polarity‐reversal catalyst (PRC) for the radical‐mediated redox rearrangements of benzylidene acetals. During the rearrangement reaction, cyclic benzylidene acetals are transformed into benzoate esters leading to a significant volumetric expansion to reduce thermoset shrinkage. We were able to show that this expansion on a molecular level reduces shrinkage and polymerization stress but does not significantly affect the (thermo‐)mechanical properties of the cross‐linked networks. One of the key advantages of this process lies in its simplicity. No additives like sensitizers or combinations of different initiators (radical and cationic) are needed. Furthermore, the same light source can be used for both the polymerization reaction and expansion through rearrangement. Additionally, the applied photoinitiator enables spatial and temporal control of the polymerization; thus, the developed system can be an excellent platform for additive manufacturing processes.

In vitro assessment of small-diameter synthetic vascular grafts usually uses standard cell culture conditions with early-passage cells. However, these conduits are mainly implanted in elderly patients and are subject to complex cellular interactions influenced by age and inflammation. Understanding these factors is central to the development of vascular grafts tailored to the specific needs of patients. In this study, the effects of aged endothelial cells subjected to pro- and anti-inflammatory agents and cultivated on a newly developed biodegradable electrospun thermoplastic polyurethane/poly(urethane-urea) blend (TPU/TPUU), on clinically available expanded polytetrafluorethylene (ePTFE), and on decellularized extracellular matrix (dECM) grafts were investigated. Young and aged endothelial cells were exposed to pro- and anti-inflammatory agents and characterized by morphology, migration capacity, and gene expression. In addition, the cells were seeded onto the various graft materials and examined microscopically alongside gene expression analyses. When exposed to pro-inflammatory cytokines, young and aged cells demonstrated signs of endothelial activation. Cells seeded on ePTFE showed reduced attachment and increased expression of pro-inflammatory genes compared with the other materials. dECM and TPU/TPUU substrates provided better support for endothelialization with aged cells under inflammatory conditions compared with ePTFE. Moreover, TPU/TPUU showed positive effects on reducing pro-thrombotic and pro-inflammatory gene expression in endothelial cells. Our results thus emphasize the importance of developing new synthetic graft materials as an alternative for clinically used ePTFE.

A highly reactive thiol-ene high internal phase emulsion based on the monomers 1,6-hexanediol diacrylate and tris 2-(3-mercaptopropionyloxy)ethyl isocyanurate was developed for the purpose of light-driven additive manufacturing, resulting in highly porous customizable poly(high internal phase emulsion) materials. The formulation was specifically designed to facilitate short irradiation times and low amounts of photoinitiator. Furthermore, the developed emulsion does not rely on employing harmful solvents to make scale-up and industrial applications feasible. The selected thiol was added to the printing formulation as a chain-transfer agent, decreasing the brittleness of the acrylate-based system and potential of oxygen inhibition. The thickness of the printed layers lay <50 mu m, and the average pore size of all samples was <5 mu m.

Photopatterned polymer brushes provide a viable option to alter the surface properties of biosensors, substrates for tissue engineering, or microelectronic implants. Although the one‐photon direct laser writing enables excellent control over pattern geometry, it has an inherently limited writing resolution caused by the used light source; moreover, no patterning of undercuts or channels is possible. This article describes the preparation of patterned polymer brushes on confined glass substrates using two‐photon‐initiated reversible addition–fragmentation chain‐transfer (2PRAFT) polymerization of N‐acryloylmorpholine as a hydrophilic model monomer. The polymer brushes prepared by 2PRAFT exhibit a height of 10 nm, as confirmed by atomic force microscopy. In addition, well‐defined printed structures down to 5 μm size are prepared, which outperforms the currently achieved resolution of polymer brushes prepared by one‐photon direct laser writing.

Controlling cellular responses to nanoparticles so far is predominantly empirical, typically requiring multiple rounds of optimization of particulate carriers. In this study, a systematic model-assisted approach should lead to the identification of key parameters that account for particle properties and their cellular recognition. A copolymer particle library was synthesized by a combinatorial approach in soap free emulsion copolymerization of styrene and methyl methacrylate, leading to a broad compositional as well as constitutional spectrum. The proposed structure-property relationships could be elucidated by multivariate analysis of the obtained experimental data, including physicochemical characteristics such as molar composition, molecular weight, particle diameter, and particle charge as well as the cellular uptake pattern of nanoparticles. It was found that the main contributors for particle size were the polymers' molecular weight and the zeta potential, while particle uptake is mainly directed by the particles' composition. This knowledge and the reported model-assisted procedure to identify relevant parameters affecting particle engulfment of particulate carriers by nonphagocytic and phagocytic cells can be of high relevance for the rational design of pharmaceutical nanocarriers and assessment of biodistribution and nanotoxicity, respectively.

We demonstrate light-based 3D printing of pure poly(ether carbonate) networks free of shrinkage stress. Expanding the recently pioneered concept of pure cationic double ring-opening photopolymerization of spiro-orthoesters at elevated temperatures, we herein investigate spiro-orthocarbonates. Thereof resulting poly(ether carbonate) networks could find manyfold applications in biological and medical settings as well as in applications searching for more sustainable material solutions. We have determined the dependence of single and double ring-opening and the presence of backbiting side reactions for three synthesized spiro-orthocarbonate monomers in combination with an oxetane crosslinker on the ring size and photopolymerization temperature to optimize the photogenerated network and thus material properties. The absence of residual stresses in the polymer network was confirmed by tracking the decrease of sample birefringence with increasing spiro-carbonate monomer content of the sample. Based on this fundamental study, the best-performing monomer was printed in combination with an oxetane crosslinker.

Vanillyl alcohol has emerged as a widely used building block for the development of biobased monomers. More specifically, the cationic (photo-)polymerization of the respective diglycidyl ether (DGEVA) is known to produce materials of outstanding thermomechanical performance. Generally, chain transfer agents (CTAs) are of interest in cationic resins not only because they lead to more homogeneous polymer networks but also because they strikingly improve the polymerization speed. Herein, the aim is to compare the cationic chain-growth photopolymerization with the thermally initiated anionic step-growth polymerization, with and without the addition of CTAs. Indeed, CTAs lead to faster polymerization reactions as well as the formation of more homogeneous networks, especially in the case of the thermal anionic step-growth polymerization. Resulting from curing above the T-G of the respective anionic step-growth polymer, materials with outstanding tensile toughness (>5 MJ cm(-3)) are obtained that result in the manufacture of potential shape-memory polymers.

Herein, miniemulsion photopolymerization is implemented as a useful tool for synthesis of waterborne poly (thioether) dispersions from biobased monomers isosorbide-based dithiol (3R,3aR,6S,6aR)-hexahydrofuro[3,2-b] furan-3,6-diyl bis(3-mercaptopropanoate) and diallyl (3R,3aR,6S,6aR)-3,6-bis(allyloxy)hexahydrofuro[3,2-b] furan and their combination with the petroleum -based dienes diallyl terephthalate, 3,9-divinyl-2,4,8,10-tetraoxaspiro [5.5]undecane, and 1,4-bis(allyloxy)benzene. The synthetic process is optimized to achieve 30 % solids content latexes with weight average molecular weight ranging from 8.2 kg/mol to 136 kg/mol. The resulting poly(thioether) latexes yield consistent continuous polymer films after water evaporation at atmospheric conditions. Poly(thioether) films based on both biobased thiol and ene are soft and sticky, and thus, present insufficient mechanical properties for coating application. On the other hand, when biobased thiol was combined with petroleum based enes with aromatic and cyclic moieties within the structure, the obtained films are rigid and film forming. Only the film based on diallyl terephthalate diene present excellent balance of stiffness and flexibility, therefore with potential for coating application. Moreover, this film shows relatively good water sensitivity, with water uptake below 20 % after 11 days of water immersion and high gloss (above 80 gloss unit) measured at 60 angle of incidence. The properties are within the range of requirements for decorative coatings applications.