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 The molecule was retracted from a strongly adhering mica surface by pulling on one of the α-chains, forcing the triple-helix to unravel.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.

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.

Three-dimensional (3D) bioinspired hydrogels have played an important role in tissue engineering, owing to their advantage of excellent biocompatibility. Here, the two-photon polymerization (TPP) of a 3D hydrogel with high precision has been investigated, using the precursor with hyaluronic acid vinyl ester (HAVE) as the biocompatibility hydrogel monomer, 3,3'-((((1E,1'E)-(2-oxocyclopentane-1,3-diylidene) bis(methanylylidene)) bis(4,1-phenylene)) bis(methylazanediyl))dipropanoate as the water-soluble initiator, and dl-dithiothreitol (DTT) as the click-chemistry cross-linker. The TPP properties of the HAVE precursors have been comprehensively investigated by adjusting the solubility and the formulation of the photoresist. The feature line width of 22 nm has been obtained at a processing laser threshold of 3.67 mW, and the 3D hydrogel scaffold structures have been fabricated. Furthermore, the average value of Young's modulus is 94 kPa for the 3D hydrogel, and cell biocompatibility has been demonstrated. This study would provide high potential for achieving a 3D hydrogel scaffold with highly precise configuration in tissue engineering and biomedicine.

The terpolymer acrylonitrile-butadiene-styrene (ABS) is a widely used thermoplastic material due to its excellent mechanical properties, especially high toughness. However, the monomer system of ABS cannot be feasibly photopolymerized due to its reactivity, opacity and monomer volatility. We show the transfer of an ABS microstructure to photopolymers via monomer systems designed to mimic ABS while remaining photopolymerizable. Acrylonitrile was substituted by more reactive and less volatile maleimides, of which the N substituent influences crosslinking considerably. Instead of styrene, less volatile derivatives were utilized as comonomers. Poly(butadiene) was introduced as cheap, readily available and non-volatile rubber. The resulting maleimide-styrene-poly(butadiene) networks exhibit varying microphase separations and simultaneous transparency. While optimized materials cannot quite exhibit the yield strain of hot-pressed ABS filament, their toughness partly exceeds that of ABS. Superior thermal stabilities and glass transition temperatures up to 190 degrees C were observed. Finally, stereolithographic printing of one tuned monomer system was conducted. (c) 2021 The Authors. Polymer International published by John Wiley & Sons Ltd on behalf of Society of Industrial Chemistry.

Vinyl ester-based monomers for radical photopolymerization have recently been shown to be promising alternatives to (meth)acrylates through lower irritancy and cytotoxicity. Vinyl ester monomers are becoming increasingly important on account of new, more cost-efficient synthetic production methods, not to forget their increased reactivity and improved material properties in combination with thiol-ene polymerization. Due to their biocompatibility and degradability, these monomers are more frequently used in tissue engineering. Nevertheless, the material properties can be improved by possible copolymerizations with other monomers. Therefore, the copolymerization behavior of vinyl ester with norbornene, allyl ether and allyl ester has been studied fundamentally in a photoreactor via free radical photopolymerization. Here, the consumption of double bonds of the monomers has been identified using NMR spectroscopy. Copolymerization parameters have been determined using the Kelen-Tudos method. Results show equal consumption of vinyl ester and co-monomer double bonds leading to alternating copolymerizations. The double bond conversion was confirmed via in situ real-time near-infrared photorheology. Mono- and difunctional vinyl esters with co-monomers have also provided further insight into the polymer network of these copolymers. (c) 2021 The Authors. Polymer International published by John Wiley & Sons Ltd on behalf of Society of Industrial Chemistry.

Adhesion processes play a decisive role in the animal and human body and have been studied in great detail. Phosphorylation of serine as adhesion strategy is found in different species and serves different purposes, e.g. under water surface adhesion and protection strategies. Based on these biological adhesion applications, we present a biomimetic phosphonate-containing block copolymer approach to study surface adhesion. We synthesized two block copolymers (28 kDa and 39 kDa), which differed in their phosphonate-containing block dimethyl(2-methacryloyloxyethyl phosphonate) (DMMEP), using reversible addition fragmentation-chain transfer (RAFT) polymerization and tethered these polymers onto atomic force microscopy (AFM) probes. After performing AFM in single molecule force spectroscopy (SMFS) mode under physiological-like conditions (phosphate buffered saline - PBS, pH 7.2) on different substrates (mica, calcium deficient hydroxyapatite, TiO2 coated Si-wafer) we determined adhesion forces of 1610 +/- 76 pN and 2257 +/- 48 pN for the 28 kDa and the 39 kDa block copolymer, respectively. Our results show higher adhesion on hydroxyapatite, TiO2 and mica using polymers with a longer phosphonate block. This phosphonate containing block copolymer could serve as adhesion motif in several applications, and is very promising in the biomedical field, especially for tissue engineering applications due to its excellent adhesion on hydroxyapatite and titanium under physiological-like conditions.

Achieving strong adhesion in wet environments remains a technological challenge in biomedical applications demanding biocompatibility. Attention for adhesive motifs meeting such demands has largely been focused on marine organisms. However, bioadhesion to inorganic surfaces is also present in the human body, in the hard tissues of teeth and bones, and is mediated through serines (S). The specific amino acid sequence DpSpSEEKC has been previously suggested to be responsible for the strong binding abilities of the protein statherin to hydroxyapatite, where pS denotes phosphorylated serine. Notably, similar sequences are present in the non-collagenous bone protein osteopontin (OPN) and the mussel foot protein 5 (Mefp5). OPN has previously been shown to promote fracture toughness and physiological damage formation. Here, we investigated the adhesion strength of the motif D(pS)(pS)EEKC on substrates of hydroxyapatite, TiO2, and mica using atomic force microscopy (AFM) single-molecule force spectroscopy (SMFS). Specifically, we investigated the dependence of adhesion force on phosphorylation of serines by comparing findings with the unphosphorylated variant DSSEEKC. Our results show that high adhesion forces of over 1 nN on hydroxyapatite and on TiO2 are only present for the phosphorylated variant D(pS)(pS)EEKC. This warrants further exploitation of this motif or similar residues in technological applications. Further, the dependence of adhesion force on phosphorylation suggests that biological systems potentially employ an adhesion-by-demand mechanism via expression of enzymes that up- or down-regulate phosphorylation, to increase or decrease adhesion forces, respectively.

UV curing of photopolymerizable monomers, like (meth)acrylates, has been utilized for coatings for more than half a century and more recently in further developed areas such as tissue engineering. However, these monomers have major disadvantages, e.g., high irritancy and cytotoxicity, which leads to limited use in tissue engineering regarding health issues. Vinyl esters (VE) and vinyl carbonates (VC) can compete with (meth)acrylates in terms of material properties and have significantly lower toxicity, but lack in cost efficient synthesis methods. The purpose of this communication is to establish new pathways to overcome this drawback. It was shown that VEs can be synthesized either by vinyloxy trimethylsilane or by acetaldehyde in excellent yields. Moreover, a new method to synthesize vinyl chloroformate as precursor for VCs in lab scale was evolved by a catalyzed reaction of vinyloxy trimethylsilane with a phosgene solution. Finally, the cytotoxicity tests showed auspicious results.

In this study, a thorough exploration of constitutional parameters of thiol-ene photocrosslinkable hydrogels based on hyaluronic acid vinyl ester was conducted in order to decipher their impact on material properties. These constitutional parameters originated from the process of synthesis (macromer size and degree of substitution) and from the process of formulation (photoinitiator concentration, macromer content, and thiol-to-ene ratio). Various macromers were obtained with a broad variety of degrees of substitution. Photorheology measurements were performed in order to determine the influence of the structure parameters on photoreactivity and the physical properties of hydrogels. Final crosslink densities and photoreactivities dramatically increase with increasing number of functional groups, macromer concentrations as well as with photoinitiator concentration. Swellabilities of the hydrogels were determined as complementary reference values. Mass swelling ratios as well as mass loss increased with decreasing degree of substitution as a result of increased mesh size and hydrophilicity. Finally, hyaluronic acid vinyl ester formulations were used to encapsulate fluorescent-labeled immortalized human adipose-derived mesenchymal stem cells in 3D via UV and by high-resolution two-photon polymerization. Cell-survival was successfully studied via confocal laser scanning microscopy during the course of 2 weeks.

ABSTRACTThermoplastic polyurethane elastomers (TPUs) with a biodegradable chain extender and different nonaromatic diisocyanate hard segments were synthesized and tested concerning their thermal, mechanical, and degradation properties and for their processability regarding electrospinning. The design of the TPUs was based on the structural modification of the hard segment using linear aliphatic hexamethylene diisocyanate (HMDI), more rigid alicyclic 4,4′‐methylene bis(cyclohexylisocyanate) (H12MDI), 1,3‐bis(isocyanatomethyl)cyclohexane (BIMC), or isophorone diisocyanate (IPDI). The soft segment consisted of poly(tetrahydrofuran). Bis(2‐hydroxyethyl) terephthalate (BET) was used as chain extender with cleavable ester bonds. Some of the polyurethanes based on alicyclic diisocyanate showed better mechanical performance than the less rigid HMDI‐based TPU. The TPU in vitro degradability was tested for 25 days at elevated temperatures in PBS buffer and indicated a bulk erosion process. Electrospinning experiments were conducted and promising results with respect to further applicability of these materials in vascular tissue engineering were obtained. © 2018 The Authors Journal of Polymer Science Part A: Polymer Chemistry Published by Wiley Periodicals, Inc. J. Polym. Sci., Part A: Polym. Chem. 2018, 56, 2214–2224

In the last few years studies of phosphorus-based polymers have attracted attention because of their large variety of applications. They have been subject of great interest in the fields of flame retardancy, adhesion promotors and tissue engineering. These phosphor-based materials, often bearing a methacrylate moiety for polymerization, are proved to be biodegradable, blood-compatible and lead to strong interactions with bones, enamel or dentin.