Search Results (10)

Tissue engineering represents a central strategy in regenerative medicine to restore damaged or missing tissue through structural and functional replacement. In this study, a two-component bioink platform was developed based on amine–anhydride conjugation as a mild crosslinking reaction between synthetic anhydride-containing oligomers (oSMoMA-x) and natural biopolymers. The compatibility of the oligomers with different amine-containing biopolymers, including chitosan, gelatin, and hydrolyzed collagen peptides, was systematically evaluated. To improve cytocompatibility and enable controlled network formation, oSMoMA oligomers with varying anhydride contents were synthesized and characterized, allowing targeted tuning of material properties through comonomer composition. The resulting hydrogels were comparatively assessed with respect to their rheological and physicochemical properties. While hydrogel formation was achieved with all investigated biopolymers, gelatin-based systems exhibited the most favorable characteristics for bioink development. Two gelatin/oSMoMA bioink formulations with distinct gelation behavior were obtained by employing different base catalysts, enabling control over crosslinking kinetics and material properties. Cytocompatibility was comprehensively evaluated using viability assays, demonstrating enhanced metabolic activity of cells encapsulated in gelatin/oSMoMA-3.5 hydrogels compared to established reference systems, with sustained compatibility for up to seven days. Extrusion-based 3D bioprinting was performed using a modified printhead with integrated temperature control to maintain physiological conditions. The bioinks were successfully printed with embedded murine 3T3 fibroblasts, and post-printing analyses confirmed cell proliferation within the hydrogel constructs. Overall, the results demonstrate the broad compatibility of amin–anhydride-crosslinked oSMoMA systems with different biopolymers and highlight gelatin/oSMoMA bioinks as promising cytocompatible materials for stable 3D bioprinting applications in tissue engineering. Full article

In this work, we studied the thermal behavior and infrared fingerprint of anhydrous and hydrated DL-tartaric acid via conventional and modulated Differential Scanning Calorimetry (DSC), Thermogravimetry (TGA), Fourier Transform Infrared Spectroscopy (FTIR), nuclear magnetic resonance (NMR), pH measurements, and ab initio density functional theory (DFT) calculations. Six samples were examined in total (raw, recrystallized from D₂O solution, freeze-dried, and three heated samples). The results reveal that both forms (anhydrous and hydrated) do not exhibit melting prior to decomposition. It is also shown that the so-called DL-tartaric acid does not exist in the solid state in pure form, but it contains water and a tartaric acid oligomer, which is produced through esterification. Alteration of the chemical structure (reflected through decomposition) is initiated at quite low temperatures and is more pronounced for the hydrated form. Up to 75 °C, decomposition proceeds through esterification, while at higher temperatures it seems to be reversed due to the increase in water and decrease in COOH groups emerging through anhydride formation. Either upon heating or at sub-zero temperatures during freeze-drying, the hydrated form decomposes, and although some water is removed, new water is produced due to esterification. The conclusions are also supported by DFT calculations. Full article

Gelatin-based hydrogels have shown good injectability and biocompatibility and have been broadly used for drug delivery and tissue regeneration. However, their low mechanical strengths and fast degradation rates must be modified for long-term implantation applications. With an aim to develop mechanically stable hydrogels, reactive anhydride-based oligomers were developed and used to fabricate gelatin-based crosslinked hydrogels in this study. A cascade of hydrophilic oligomers containing reactive anhydride groups was synthesized by free radical polymerization. These oligomers varied in degree of reactivity, comonomer composition, and showed low molecular weights (M_n < 5 kDa). The reactive oligomers were utilized to fabricate hydrogels that differed in their mechanical strengths and degradation profiles. These formulations exhibited good cytocompatibility with human adipose tissue-derived stem cells (hADCs). In conclusion, the reactive MA-containing oligomers were successfully synthesized and utilized for the development of oligomer-crosslinked hydrogels. Such oligomer-crosslinked gelatin-based hydrogels hold promise as drug or cell carriers in various biomedical applications. Full article

The local release of complexed siRNA from biomaterials opens precisely targeted therapeutic options. In this study, complexed siRNA was loaded to gelatin microparticles cross-linked (cGM) with an anhydride-containing oligomer (oPNMA). We aggregated these siRNA-loaded cGM with human mesenchymal stem cells (hMSC) to microtissues and stimulated them with osteogenic supplements. An efficient knockdown of chordin, a BMP-2 antagonist, caused a remarkably increased alkaline phosphatase (ALP) activity in the microtissues. cGM, as a component of microtissues, mineralized in a differentiation medium within 8–9 days, both in the presence and in the absence of cells. In order to investigate the effects of our pre-differentiated and chordin-silenced microtissues on bone homeostasis, we simulated in vivo conditions in an unstimulated co-culture system of hMSC and human peripheral blood mononuclear cells (hPBMC). We found enhanced ALP activity and osteoprotegerin (OPG) secretion in the model system compared to control microtissues. Our results suggest osteoanabolic effects of pre-differentiated and chordin-silenced microtissues. Full article

New organophilic montmorillonites with oligomers of lactic acid and other compounds such as citric acid, stearic acid, maleic anhydride, pentaerythritol and ε-caprolactone were synthesized. They were characterized by Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Thermogravimetric Analysis (TGA), Scanning Electron Microscopy (SEM), elemental analysis and swelling capacity in water. In all tested composites, an increase in the montmorillonite interlayer distance resulting from intercalation of the modifying substance in the montmorillonite was found by means of XRD. Elemental analysis and FTIR showed that all of the tested samples contained an organic segment in the montmorillonite structure. TGA studies revealed that composites modified with lactic acid oligomers, stearic acid or ε-caprolactone had the highest thermal stability. They also exhibited the lowest swelling capacity which was 2–3 times lower than that for unmodified sodium montmorillonite. Some preliminary studies on the mechanical properties of PLA/modified montmorillonite are also presented and discussed. Full article

The performance of artificial nerve guidance conduits (NGC) in peripheral nerve regeneration can be improved by providing structures with multiple small channels instead of a single wide lumen. 3D-printing is a strategy to access such multi-channeled structures in a defined and reproducible way. This study explores extrusion-based 3D-printing of two-component hydrogels from a single cartridge printhead into multi-channeled structures under aseptic conditions. The gels are based on a platform of synthetic, anhydride-containing oligomers for cross-linking of gelatinous peptides. Stable constructs with continuous small channels and a variety of footprints and sizes were successfully generated from formulations containing either an organic or inorganic gelation base. The adjustability of the system was investigated by varying the cross-linking oligomer and substituting the gelation bases controlling the cross-linking kinetics. Formulations with organic N‑methyl-piperidin-3-ol and inorganic K₂HPO₄ yielded hydrogels with comparable properties after manual processing and extrusion-based 3D-printing. The slower reaction kinetics of formulations with K₂HPO₄ can be beneficial for extending the time frame for printing. The two-component hydrogels displayed both slow hydrolytic and activity-dependent enzymatic degradability. Together with satisfying in vitro cell proliferation data, these results indicate the suitability of our cross-linked hydrogels as multi-channeled NGC for enhanced peripheral nerve regeneration. Full article

Cross-linking is an effective way to enhance biodegradable poly(propylene carbonate) (PPC) from CO₂ and propylene oxide (PO). Cross-linked PPC can be prepared by one-step terpolymerization of multifunctional third monomers with CO₂ and PO. However, few such third monomers are available. Each molecule of maleic anhydride oligomer (MAO) contains more than two cyclic anhydride groups. Here, we use it to synthesize PPC with cross-linked networks by adding a small quantity of MAO (0.625–5 wt% of PO) in CO₂/PO copolymerization that was catalyzed by zinc glutarate. The formation of networks in the prepared copolymers was confirmed by the presence of gel in copolymers combined Fourier transform infrared spectroscopy (FT-IR), ¹H NMR, and the improved mechanical properties. The 5% weight-loss degradation temperatures and maximum weight-loss degradation temperatures greatly increase up to 289.8 °C and 308.8 °C, respectively, which are remarkably high when compared to those of PPC. The minimum permanent deformation of the copolymers closes to 0, while that of PPC is 173%. The maximum tensile strength of the copolymers is 25.5 MPa higher than that of PPC, reaching 38.4 MPa, and it still has some toughness with the elongation at break of 25%. The above phenomena indicate that MAO that was inserted in PPC chains play a cross-linking role, which results in enhanced thermal stability, dimensional stability, and mechanical strength, comprehensively. Full article

Palm fatty acid distillate (PFAD), is a by-product of the crude palm oil refining process. It comprises mainly of free fatty acids—around 45% palmitic and 33% oleic acids—as the major components. Ultra-violet (UV) curable urethane acrylate (UA) oligomers could be synthesized from PFAD, by the following procedure. A hydroxyl terminated macromer was first prepared by reacting PFAD with a mixture of isophthalic acid, phthalic anhydride, neopentagylcol (NPG), and pentaerythritol. The macromer was then reacted with 2-hydroxylethylacrylate (2HEA) and toluene diisocynate (TDI) to generate a resin, containing acrylate side chains for UV curable application. A series of UA resins were prepared by using 15, 25, 45, 55, and 70% of PFAD, respectively. The UA resin has M_w in the range of 3,200 to 27,000. They could be cured by UV irradiation at an intensity of 225 mW/cm². Glass transition temperature (T_g) of the cured film was measured by differential scanning calorimeter (DSC), and hardness of the film was determined by a pendulum hardness tester, according to American Society for Testing and Materials (ASTM)4366. The resins were used in a wood-coating application. All of the cured films showed good adhesion, hardness, and chemical resistance except for the one using the 70% PFAD, which did not cure properly. Full article

Toward the next generation of nerve guidance conduits (NGCs), novel biomaterials and functionalization concepts are required to address clinical demands in peripheral nerve regeneration (PNR). As a biological polymer with bioactive motifs, gelatinous peptides are promising building blocks. In combination with an anhydride-containing oligomer, a dual-component hydrogel system (cGEL) was established. First, hollow cGEL tubes were fabricated by a continuous dosing and templating process. Conduits were characterized concerning their mechanical strength, in vitro and in vivo degradation and biocompatibility. Second, cGEL was reformulated as injectable shear thinning filler for established NGCs, here tyrosine-derived polycarbonate-based braided conduits. Thereby, the formulation contained the small molecule LM11A-31. The biofunctionalized cGEL filler was assessed regarding building block integration, mechanical properties, in vitro cytotoxicity, and growth permissive effects on human adipose tissue-derived stem cells. A positive in vitro evaluation motivated further application of the filler material in a sciatic nerve defect. Compared to the empty conduit and pristine cGEL, the functionalization performed superior, though the autologous nerve graft remains the gold standard. In conclusion, LM11A-31 functionalized cGEL filler with extracellular matrix (ECM)-like characteristics and specific biochemical cues holds great potential to support PNR. Full article

Laboratory preparations of liquid crystalline prepolymers, distillates accompanying prepolymers, final polymers, and sublimates accompanying final polymers were examined. NaOD/D₂O depolymerization of prepolymers and polymers back to monomers with integration of the ¹H NMR spectra showed up to 6% excess of carboxyls over phenol groups, caused partly by loss of the low-boiling comonomer hydroquinone through distillation during prepolymerization and leaving anhydride units in the polymer chain. ESI⁻ MS and MS/MS of hexafluoroisopropanol extracts of the prepolymer detected small molecules including some containing anhydride groups; ESI⁺ MS showed the presence of small cyclic oligomers. ¹H NMR (including TOCSY) spectra provided more quantitative analyses of these oligomers. The final polymerization increases the length of the polymer chains and sublimes out the small oligomers. Anhydride linkages remaining in the polymer must make LCP’s more susceptible to degradation by nucleophilic reagents such as water, alkalis, and amines. Full article