Amides as Non-polymerizable Catalytic Adjuncts Enable the Ring-Opening Polymerization of Lactide With Ferrous Acetate Under Mild Conditions

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

Insights from Multimodal Preclinical Imaging in Immunocompetent Nude Mice

Hydrogels based on gelatin have evolved as promising multifunctional biomaterials. Gelatin is crosslinked with lysine diisocyanate ethyl ester (LDI) and the molar ratio of gelatin and LDI in the starting material mixture determines elastic properties of the resulting hydrogel. In order to investigate the clinical potential of these biopolymers, hydrogels with different ratios of gelatin and diisocyanate (3-fold (G10_LNCO3) and 8-fold (G10_LNCO8) molar excess of isocyanate groups) were subcutaneously implanted in mice (uni- or bilateral implantation). Degradation and biomaterial-tissue- interaction were investigated in vivo (MRI, optical imaging, PET) and ex vivo (autoradiography, histology, serum analysis). Multimodal imaging revealed that the number of covalent net points correlates well with degradation time, which allows for targeted modification of hydrogels based on properties of the tissue to be replaced. Importantly, the degradation time was also dependent on the number of implants per animal. Despite local mechanisms of tissue remodeling no adverse tissue responses could be observed neither locally nor systemically. Finally, this preclinical investigation in immunocompetent mice clearly demonstrated a complete restoration of the original healthy tissue

Multivalent grafting of hyperbranched oligo- and polyglycerols shielding rough membranes to mediate hemocompatibility

Hemocompatible materials are needed for internal and extracorporeal biomedical applications, which should be realizable by reducing protein and thrombocyte adhesion to such materials. Polyethers have been demonstrated to be highly efficient in this respect on smooth surfaces. Here, we investigate the grafting of oligo- and polyglycerols to rough poly(ether imide) membranes as a polymer relevant to biomedical applications and show the reduction of protein and thrombocyte adhesion as well as thrombocyte activation. It could be demonstrated that, by performing surface grafting with oligo- and polyglycerols of relatively high polydispersity (>1.5) and several reactive groups for surface anchoring, full surface shielding can be reached, which leads to reduced protein adsorption of albumin and fibrinogen. In addition, adherent thrombocytes were not activated. This could be clearly shown by immunostaining adherent proteins and analyzing the thrombocyte covered area. The presented work provides an important strategy for the development of application relevant hemocompatible 3D structured materials

Enzymatic action as switch of bulk to surface degradation of clicked gelatin-based networks

Polymer degradation occurs under physiological conditions in vitro and in vivo, especially when bonds susceptible to hydrolysis are present in the polymer. Understanding of the degradation mechanism, changes of material properties over time, and overall rate of degradation is a necessary prerequisite for the knowledge-based design of polymers with applications in biomedicine. Here, hydrolytic degradation studies of gelatin-based networks synthesized by copper-catalyzed azide-alkyne cycloaddition reaction are reported, which were performed with or without addition of an enzyme. In all cases, networks with a stilbene as crosslinker proofed to be more resistant to degradation than when an octyl diazide was used. Without addition of an enzyme, the rate of degradation was ruled by the crosslinking density of the network and proceeded via a bulk degradation mechanism. Addition of Clostridium histolyticum collagenase resulted in a much enhanced rate of degradation, which furthermore occurred via surface erosion. The mesh size of the hydrogels (>7 nm) was in all cases larger than the hydrodynamic radius of the enzyme (4.5 nm) so that even in very hydrophilic networks with large mesh size enzymes may be used to induce a fast surface degradation mechanism. This observation is of general interest when designing hydrogels to be applied in the presence of enzymes, as the degradation mechanism and material performance are closely interlinkedstatus: publishe

Advanced Functional Polymers for Medicine

No abstract is available for this article

Design of decorin-based peptides that bind to collagen I and their potential as adhesion moieties in biomaterials

Mimicking the binding epitopes of protein-protein interactions by using small peptides is important for generating modular biomimetic systems. A strategy is described for the design of such bioactive peptides without accessible structural data for the targeted interaction, and the effect of incorporating such adhesion peptides in complex biomaterial systems is demonstrated. The highly repetitive structure of decorin was analyzed to identify peptides that are representative of the inner and outer surface, and it was shown that only peptides based on the inner surface of decorin bind to collagen. The peptide with the highest binding affinity for collagen I, LHERHLNNN, served to slow down the diffusion of a conjugated dye in a collagen gel, while its dimer could physically crosslink collagen, thereby enhancing the elastic modulus of the gel by one order of magnitude. These results show the potential of the identified peptides for the design of biomaterials for applications in regenerative medicine.status: publishe

Bio-Inspired Magnetically Controlled Reversibly Actuating Multimaterial Fibers

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