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Abstract In situ hydrogelation of injectable precursors upon biological stimulus is relevant to generate hydrogels under mild conditions and, potentially, at a biological side of interest. Here, it is shown that hydrolytic enzymes can be used to initiate the formation of covalent hydrogel networks, realizing a cleavage‐leading‐to‐gelation strategy. For this purpose, a two‐component system is used, consisting of a 4‐arm polyethylene glycol‐thiodepsipeptide conjugate, PEG4TDPo containing the matrix metalloproteinases MMP‐2‐ and MMP‐9‐cleavable Ac‐Pro‐Leu‐Gly#SLeu‐Leu‐Gly‐ thiodepsipeptide sequence releasing a thiol upon hydrolysis, and a maleimide functionalized 4‐armed PEG (PEG4MAL). PEG4TDPo is synthesized in a PEG‐functionalization protocol involving convergent and divergent synthetic steps without the need for rigorous purification procedures. In a fluorometric assay, it is shown that the construct is in fact cleaved by both investigated MMPs. PEG4TDPo in the presence of 10 wt.% PEG4MAL formed hydrogels upon addition of MMP‐2 or ‐9 with average gelation times of 28 and 40 min, respectively, as is investigated by rheology. The much faster gelation times compared to the enzyme‐free system showed the specific input of the enzymatic reactions. The MMP‐assisted activation and crosslinking strategy can potentially become useful by targeting tissues showing an increased expression of MMPs, such as cancers, or to detect MMPs.

At a time when environmental considerations are increasingly pushing for the application of circular economy concepts in materials science, lignin stands out as an under-used but promising and environmentally benign building block. This review focuses (A) on understanding what we mean with lignin, i.e., where it can be found and how it is produced in plants, devoting particular attention to the identity of lignols (including ferulates that are instrumental for integrating lignin with cell wall polysaccharides) and to the details of their coupling reactions and (B) on providing an overview how lignin can actually be employed as a component of materials in healthcare and energy applications, finally paying specific attention to the use of lignin in the development of organic shape-memory materials.

Movements in plants, such as the coiling of tendrils in climbing plants, have been studied as inspiration for coiling actuators in robotics. A promising approach to mimic this behavior is the use of multimaterial systems that show different elastic moduli. Here, we report on the development of magnetically controllable/triggerable multimaterial fibers (MMFs) as artificial tendrils, which can reversibly coil and uncoil on stimulation from an alternating magnetic field. These MMFs are based on deformed shape-memory fibers with poly[ethylene-co-(vinyl acetate)] (PEVA) as their core and a silicone-based soft elastomeric magnetic nanocomposite shell. The core fiber provides a temperature-dependent expansion/contraction that propagates the coiling of the MMF, while the shell enables inductive heating to actuate the movements in these MMFs. Composites with mNP weight content ≥ 15 wt% were required to achieve heating suitable to initiate movement. The MMFs coil upon application of the magnetic field, in which a degree of coiling N = 0.8 ± 0.2 was achieved. Cooling upon switching OFF the magnetic field reversed some of the coiling, giving a reversible change in coiling ∆n = 2 ± 0.5. These MMFs allow magnetically controlled remote and reversible actuation in artificial (soft) plant-like tendrils, and are envisioned as fiber actuators in future robotics applications.

Cell–material interactions are the defining feature of biomaterials, and they are relevant for evaluating material residues and pollutants [...]

High crystallization rate and thermomechanical stability make polylactide stereocomplexes effective nanosized physical netpoints. Here, we address the need for soft, form-stable degradable elastomers for medical applications by designing such blends from (co)polyesters, whose mechanical properties are ruled by their nanodimensional architecture and which are applied as single components in implants. By careful controlling of the copolymer composition and sequence structure of poly[(L-lactide)-co-(ε-caprolactone)], it is possible to prepare hyperelastic polymer blends formed through stereocomplexation by adding poly(D-lactide) (PDLA). Low glass transition temperature Tg ≤ 0 °C of the mixed amorphous phase contributes to the low Young’s modulus E. The formation of stereocomplexes is shown in DSC by melting transitions Tm > 190 °C and in WAXS by distinct scattering maxima at 2θ = 12° and 21°. Tensile testing demonstrated that the blends are soft (E = 12–80 MPa) and show an excellent hyperelastic recovery Rrec = 66–85% while having high elongation at break εb up to >1000%. These properties of the blends are attained only when the copolymer has 56–62 wt% lactide content, a weight average molar mass >140 kg·mol−1, and number average lactide sequence length ≥4.8, while the blend is formed with a content of 5–10 wt% of PDLA. The devised strategy to identify a suitable copolymer for stereocomplexation and blend formation is transferable to further polymer systems and will support the development of thermoplastic elastomers suitable for medical applications.

Sn-based catalysts are effective in the ring-opening polymerization (ROP) but are toxic. Fe(OAc)2 used as an alternative catalyst is suitable for the ROP of lactide only at higher temperatures (>170°C), associated with racemization. In the ROP of ester and amide group containing morpholinediones with Fe(OAc)2 to polydepsipeptides at 135°C, ester bonds were selectively opened. Here, it was hypothesized that ROP of lactones is possible with Fe(OAc)2 when amides are present in the reactions mixture as Fe-ligands could increase the solubility and activity of the metal catalytic center. The ROP of lactide in the melt with Fe(OAc)2 is possible at temperatures as low as 105°C, in the presence of N-ethylacetamide or N-methylbenzamide as non-polymerizable catalytic adjuncts (NPCA), with high conversion (up to 99 mol%) and yield (up to 88 mol%). Polydispersities of polylactide decreased with decreasing reaction temperature to ≤ 1.1. NMR as well as polarimetric studies showed that no racemization occurred at reaction temperatures ≤145°C. A kinetic study demonstrated a living chain-growth mechanism. MALDI analysis revealed that no side reactions (e.g., cyclization) occurred, though transesterification took place.

Shape-memory hydrogels (SMH) are multifunctional, actively-moving polymers of interest in biomedicine. In loosely crosslinked polymer networks, gelatin chains may form triple helices, which can act as temporary net points in SMH, depending on the presence of salts. Here, we show programming and initiation of the shape-memory effect of such networks based on a thermomechanical process compatible with the physiological environment. The SMH were synthesized by reaction of glycidylmethacrylated gelatin with oligo(ethylene glycol) (OEG) α,ω-dithiols of varying crosslinker length and amount. Triple helicalization of gelatin chains is shown directly by wide-angle X-ray scattering and indirectly via the mechanical behavior at different temperatures. The ability to form triple helices increased with the molar mass of the crosslinker. Hydrogels had storage moduli of 0.27–23 kPa and Young’s moduli of 215–360 kPa at 4 °C. The hydrogels were hydrolytically degradable, with full degradation to water-soluble products within one week at 37 °C and pH = 7.4. A thermally-induced shape-memory effect is demonstrated in bending as well as in compression tests, in which shape recovery with excellent shape-recovery rates Rr close to 100% were observed. In the future, the material presented here could be applied, e.g., as self-anchoring devices mechanically resembling the extracellular matrix.

The single and triple helical organization of protein chains strongly influences the mechanical properties of gelatin-based materials. A chemical method for obtaining different degrees of helical organization in gelatin is covalent functionalization, while a physical method for achieving the same goal is the variation of the drying conditions of gelatin solutions. Here we explored how the introduction of desaminotyrosine (DAT) and desaminotyrosyl tyrosine (DATT) linked to lysine residues of gelatin influenced the kinetics and thermodynamic equilibrium of the helicalization process of single and triple helices following different drying conditions. Drying at a temperature above the helix-to-coil transition temperature of gelatin (T> Tc, called vshort) generally resulted in gelatins with relatively lower triple helical content (Xc,t= 1−2%) than lower temperature drying (T< Tc, called vlong) (Xc,t= 8−10%), where the DAT(T) functional groups generally disrupted helix formation. While different helical contents affected the thermal transition temperatures only slightly, the mechanical properties were strongly affected for swollen hydrogels (E= 4−13 kPa for samples treated by vlongand E= 120−700 kPa for samples treated by vshort). This study shows that side group functionalization and different drying conditions are viable options to control the helicalization and macroscopic properties of gelatin-based materials. [ABSTRACT FROM AUTHOR]

We recently reported the design and synthesis of a CD4 binding peptidomimetic with potential as HIV entry inhibitor. Variation of side chains and amino terminus provided first structure−activity relationships and confirmed the activity of the compounds as well as the correctness of our approach Neffe, A. T.; Bilang, M.; Meyer, B. Org. Biomol. Chem.2006, 4, 3259−3267. Here we describe optimizations at the carboxy terminus of the peptidomimetic CD4 ligands resulting in the highest binding affinity of KD6 M for compound 4determined with surface plasmon resonance (SPR). Saturation transfer difference NMR experiments with two peptidomimetics give binding constants similar to the SPR experiments and verified the ligand binding epitope. The higher proteolytic stability of the peptidomimetics compared to the lead peptide is demonstrated in a pronase digestion assay. Comparison of modeling and analytical data shows good agreement of theoretical and practical experiments. [ABSTRACT FROM AUTHOR]