Perfluorophenyl azide functionalization of electrospun poly(para‐dioxanone)

Strategies to surface‐functionalize scaffolds by covalent binding of biologically active compounds are of fundamental interest to control the interactions between scaffolds and biomolecules or cells. Poly(para‐dioxanone) (PPDO) is a clinically established polymer that has shown potential as temporary implant, eg, for the reconstruction of the inferior vena cava, as a nonwoven fiber mesh. However, PPDO lacks suitable chemical groups for covalent functionalization. Furthermore, PPDO is highly sensitive to hydrolysis, reflected by short in vivo half‐life times and degradation during storage. Establishing a method for covalent functionalization without degradation of this hydrolyzable polymer is therefore important to enable the surface tailoring for tissue engineering applications. It was hypothesized that treatment of PPDO with an N‐hydroxysuccinimide ester group bearing perfluorophenyl azide (PFPA) under UV irradiation would allow efficient surface functionalization of the scaffold. X‐ray photoelectron spectroscopy and attenuated total reflectance Fourier‐transformed infrared spectroscopy investigation revealed the successful binding, while a gel permeation chromatography study showed that degradation did not occur under these conditions. Coupling of a rhodamine dye to the N‐hydroxysuccinimide esters on the surface of a PFPA‐functionalized scaffold via its amine linker showed a homogenous staining of the PPDO in laser confocal microscopy. The PFPA method is therefore applicable even to the surface functionalization of hydrolytically labile polymers, and it was demonstrated that PFPA chemistry may serve as a versatile tool for the (bio‐)functionalization of PPDO scaffolds

Functionalizable coaxial PLLA/PDLA nanofibers with stereocomplexes at the internal interface

Multifunctionality of electrospun polylactic acid (PLA) nonwovens was generated by the morphological design of nanofibers. Coaxial fibers with a lower number average molar mass Mn PLLA core and a higher Mn PDLA shell form PDLA–PLLA stereocrystals at the interface, induced by annealing. In tensile tests under physiological conditions, the core–shell fibers with higher crystallinity (22% compared to 11–14%) had lower Young’s moduli E (9 ± 1 MPa) and lower elongation at break εb (26 ± 3%) than PDLA alone (E = 31 ± 9 MPa, εb = 80 ± 5%), which can be attributed to simultaneous crystallization and relaxation effects. Gelatin incorporated in the PDLA phase was presented on the outer surface providing a biointerface putatively favorable for cell adherence. Gelatin incorporation did not influence the crystallization behavior but slightly lowered Tg (60 → 54 °C). Employing exclusively polymers established in the clinic, multifunctionality was generated by design

RGD constructs with physical anchor groups as polymer co-electrospinnable cell adhesives

The tissue integration of synthetic polymers can be promoted by displaying RGD peptides at the biointerface with the objective of enhancing colonization of the material by endogenous cells. A firm but flexible attachment of the peptide to the polymer matrix, still allowing interaction with receptors, is therefore of interest. Here, the covalent coupling of flexible physical anchor groups, allowing for temporary immobilization on polymeric surfaces via hydrophobic or dipole–dipole interactions, to a RGD peptide was investigated. For this purpose, a stearate or an oligo(ethylene glycol) (OEG) was attached to GRGDS in 51–69% yield. The obtained RGD linker constructs were characterized by NMR, IR and MALDI-ToF mass spectrometry, revealing that the commercially available OEG and stearate linkers are in fact mixtures of similar compounds. The RGD linker constructs were co-electrospun with poly(p-dioxanone) (PPDO). After electrospinning, nitrogen could be detected on the surface of the PPDO fibers by X-ray photoelectron spectroscopy. The nitrogen content exceeded the calculated value for the homogeneous material mixture suggesting a pronounced presentation of the peptide on the fiber surface. Increasing amounts of RGD linker constructs in the electrospinning solution did not lead to a detection of an increased amount of peptide on the scaffold surface, suggesting inhomogeneous distribution of the peptide on the PPDO fiber surface. Human adipose-derived stem cells cultured on the patches showed similar viability as when cultured on PPDO containing pristine RGD. The fully characterized RGD linker constructs could serve as valuable tools for the further development of tissue-integrating polymeric scaffolds

One step creation of multifunctional 3D architectured hydrogels inducing bone regeneration

Structured hydrogels showing form stability and elastic properties individually tailorable on different length scales are accessible in a one-step process. They support cell adhesion and differentiation and display growing pore size during degradation. In vivo experiments demonstrate their efficacy in biomaterial-induced bone regeneration, not requiring addition of cells or growth factors

Synthesis and characterization of gelatin fragments obtained by controlled degradation

Telechelic oligomers are attractive starting materials for the preparation of materials with tailorable properties. Here, peptide chains with defined molecular weight were obtained by controlled degradation of gelatin with hydroxylamine, which resulted in the cleavage of asparaginyl-glycine bonds and formation of new aspartyl hydroxamates and amino endgroups. The reaction of gelatin with hydroxylamine resulted in fragments with molecular weights of 15, 25, 37, and 50 kDa (determined by SDS-PAGE) independently of the reaction time and conditions. The fragment mixture showed typical single and triple helical organization in WAXS spectra, but rheological studies showed lower G′ and G″ values for gels from the fragment mixture than from gelatin, and lower gel-sol transitions temperatures. A more narrow distribution was found for the fragment mixture (M n = 25 kDa, PDI = 1.4) than for commercial gelatin. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Synthesis and characterization of gelatin fragments obtained by controlled degradation

Telechelic oligomers are attractive starting materials for the preparation of materials with tailorable properties. Here, peptide chains with defined molecular weight were obtained by controlled degradation of gelatin with hydroxylamine, which resulted in the cleavage of asparaginyl-glycine bonds and formation of new aspartyl hydroxamates and amino endgroups. The reaction of gelatin with hydroxylamine resulted in fragments with molecular weights of 15, 25, 37, and 50 kDa (determined by SDS-PAGE) independently of the reaction time and conditions. The fragment mixture showed typical single and triple helical organization in WAXS spectra, but rheological studies showed lower G′ and G″ values for gels from the fragment mixture than from gelatin, and lower gel-sol transitions temperatures. A more narrow distribution was found for the fragment mixture (M n = 25 kDa, PDI = 1.4) than for commercial gelatin. Copyright © 2011 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim

Hyaluronic acid-based hydrogels crosslinked by copper-catalyzed azide-alkyne cycloaddition with tailorable mechanical properties.

Biopolymers of the extracellular matrix are attractive starting materials for providing degradable and biocompatible biomaterials. In this study, hyaluronic acid-based hydrogels with tunable mechanical properties were prepared by the use of copper- catalyzed azide-alkyne cycloaddition (known as "click chemistry"). Alkyne-functionalized hyaluronic acid was crosslinked with linkers having two terminal azide functionalities, varying crosslinker density as well as the lengths and rigidity of the linker molecules. By variation of the crosslinker density and crosslinker type, hydrogels with elastic moduli in the range of 0.5-4 kPa were prepared. The washed materials contained a maximum of 6.8 mg copper per kg dry weight and the eluate of the gel crosslinked with diazidostilbene did not show toxic effects on L929 cells. The hyaluronic acid-based hydrogels have potential as biomaterials for cell culture or soft tissue regeneration applications

Hyaluronic acid-based hydrogels crosslinked by copper-catalyzed azide-alkyne cycloaddition with tailorable mechanical properties.

Biopolymers of the extracellular matrix are attractive starting materials for providing degradable and biocompatible biomaterials. In this study, hyaluronic acid-based hydrogels with tunable mechanical properties were prepared by the use of copper- catalyzed azide-alkyne cycloaddition (known as "click chemistry"). Alkyne-functionalized hyaluronic acid was crosslinked with linkers having two terminal azide functionalities, varying crosslinker density as well as the lengths and rigidity of the linker molecules. By variation of the crosslinker density and crosslinker type, hydrogels with elastic moduli in the range of 0.5-4 kPa were prepared. The washed materials contained a maximum of 6.8 mg copper per kg dry weight and the eluate of the gel crosslinked with diazidostilbene did not show toxic effects on L929 cells. The hyaluronic acid-based hydrogels have potential as biomaterials for cell culture or soft tissue regeneration applications

Hydrogels: one step creation of multifunctional 3D architectured hydrogels inducing bone regeneration.

The back cover highlights the unique degradation behavior of hydrogels with 3D architectures (ArcGels). Hydrolytic cleavage of bonds results in a merging of pores, comparable to soap bubbles. This mechanism, described by A. Lendlein and co-workers on page 1738, results in pore growth during degradation, which putatively leads to mechanical stimulation of cells during the in vivo regeneration of bone