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- ItemGlycerylphytate as an ionic crosslinker for 3D printing of multi-layered scaffolds with improved shape fidelity and biological features(London : Royal Society of Chemistry, 2020) Mora-Boza, A.; Włodarczyk-Biegun, M.K.; Del Campo, A.; Vázquez-Lasa, B.; Román, J.S.The fabrication of intricate and long-term stable 3D polymeric scaffolds by a 3D printing technique is still a challenge. In the biomedical field, hydrogel materials are very frequently used because of their excellent biocompatibility and biodegradability, however the improvement of their processability and mechanical properties is still required. This paper reports the fabrication of dual crosslinked 3D scaffolds using a low concentrated (<10 wt%) ink of gelatin methacryloyl (GelMA)/chitosan and a novel crosslinking agent, glycerylphytate (G1Phy) to overcome the current limitations in the 3D printing field using hydrogels. The applied methodology consisted of a first ultraviolet light (UV) photopolymerization followed by a post-printing ionic crosslinking treatment with G1Phy. This crosslinker provides a robust framework and avoids the necessity of neutralization with strong bases. The blend ink showed shear-thinning behavior and excellent printability in the form of a straight and homogeneous filament. UV curing was undertaken simultaneously to 3D deposition, which enhanced precision and shape fidelity (resolution ≈150 μm), and prevented the collapse of the subsequent printed layers (up to 28 layers). In the second step, the novel G1Phy ionic crosslinker agent provided swelling and long term stability properties to the 3D scaffolds. The multi-layered printed scaffolds were mechanically stable under physiological conditions for at least one month. Preliminary in vitro assays using L929 fibroblasts showed very promising results in terms of adhesion, spreading, and proliferation in comparison to other phosphate-based traditional crosslinkers (i.e. TPP). We envision that the proposed combination of the blend ink and 3D printing approach can have widespread applications in the regeneration of soft tissues.
- ItemA “built-up” composite film with synergistic functionalities on Mg–2Zn–1Mn bioresorbable stents improves corrosion control effects and biocompatibility([Bejing] : KeAi Publishing, 2023) Dou, Zhenglong; Chen, Shuiling; Wang, Jiacheng; Xia, Li; Maitz, Manfred F.; Tu, Qiufen; Zhang, Wentai; Yang, Zhilu; Huang, NanControl of premature corrosion of magnesium (Mg) alloy bioresorbable stents (BRS) is frequently achieved by the addition of rare earth elements. However, limited long-term experience with these elements causes concerns for clinical application and alternative methods of corrosion control are sought after. Herein, we report a “built-up” composite film consisting of a bottom layer of MgF2 conversion coating, a sandwich layer of a poly (1, 3-trimethylene carbonate) (PTMC) and 3-aminopropyl triethoxysilane (APTES) co-spray coating (PA) and on top a layer of poly (lactic-co-glycolic acid) (PLGA) ultrasonic spray coating to decorate the rare earth element-free Mg–2Zn–1Mn (ZM21) BRS for tailoring both corrosion resistance and biological functions. The developed “built-up” composite film shows synergistic functionalities, allowing the compression and expansion of the coated ZM21 BRS on an angioplasty balloon without cracking or peeling. Of special importance is that the synergistic corrosion control effects of the “built-up” composite film allow for maintaining the mechanical integrity of stents for up to 3 months, where complete biodegradation and no foreign matter residue were observed about half a year after implantation in rabbit iliac arteries. Moreover, the functionalized ZM21 BRS accomplished re-endothelialization within one month.
- ItemInteraction between immobilized polyelectrolyte complex nanoparticles and human mesenchymal stromal cells(Auckland : DOVE Medical Press, 2014) Woltmann, B.; Torger, B.; Müller, M.; Hempel, U.Background: Implant loosening or deficient osseointegration is a major problem in patients with systemic bone diseases (eg, osteoporosis). For this reason, the stimulation of the regional cell population by local and sustained drug delivery at the bone/implant interface to induce the formation of a mechanical stable bone is promising. The purpose of this study was to investigate the interaction of polymer-based nanoparticles with human bone marrow-derived cells, considering nanoparticles' composition and surface net charge. Materials and methods: Polyelectrolyte complex nanoparticles (PECNPs) composed of the polycations poly(ethyleneimine) (PEI), poly(L-lysine) (PLL), or (N,N-diethylamino)ethyldextran (DEAE) in combination with the polyanions dextran sulfate (DS) or cellulose sulfate (CS) were prepared. PECNPs' physicochemical properties (size, net charge) were characterized by dynamic light scattering and particle charge detector measurements. Biocompatibility was investigated using human mesenchymal stromal cells (hMSCs) cultured on immobilized PECNP films (5-50 nmol·cm-2) by analysis for metabolic activity of hMSCs in dependence of PECNP surface concentration by MTS (3-[4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium, inner salt) assay, as well as cell morphology (phase contrast microscopy). Results: PECNPs ranging between ~50 nm and 150 nm were prepared. By varying the ratio of polycations and polyanions, PECNPs with a slightly positive (PEC+NP) or negative (PEC-NP) net charge were obtained. The PECNP composition significantly affected cell morphology and metabolic activity, whereas the net charge had a negligible influence. Therefore, we classified PECNPs into "variant systems" featuring a significant dose dependency of metabolic activity (DEAE/CS, PEI/DS) and "invariant systems" lacking such a dependency (DEAE/DS, PEI/CS). Immunofluorescence imaging of fluorescein isothiocyanate isomer I (FITC)-labeled PECNPs suggested internalization into hMSCs remaining stable for 8 days. Conclusion: Our study demonstrated that PECNP composition affects hMSC behavior. In particular, the PEI/CS system showed biocompatibility in a wide concentration range, representing a suitable system for local drug delivery from PECNP-functionalized bone substitute materials.
- ItemFunctionalization of Ti-40Nb implant material with strontium by reactive sputtering(London : BioMed Central, 2017-10-10) Göttlicher, Markus; Rohnke, Marcus; Moryson, Yannik; Thomas, Jürgen; Sann, Joachim; Lode, Anja; Schumacher, Matthias; Schmidt, Romy; Pilz, Stefan; Gebert, Annett; Gemming, Thomas; Janek, JürgenBackground: Surface functionalization of orthopedic implants with pharmaceutically active agents is a modern approach to enhance osseointegration in systemically altered bone. A local release of strontium, a verified bone building therapeutic agent, at the fracture site would diminish side effects, which could occur otherwise by oral administration. Strontium surface functionalization of specially designed titanium-niobium (Ti-40Nb) implant alloy would provide an advanced implant system that is mechanically adapted to altered bone with the ability to stimulate bone formation. Methods: Strontium-containing coatings were prepared by reactive sputtering of strontium chloride (SrCl2) in a self-constructed capacitively coupled radio frequency (RF) plasma reactor. Film morphology, structure and composition were investigated by scanning electron microscopy (SEM), time of flight secondary ion mass spectrometry (ToF-SIMS) and X-ray photoelectron spectroscopy (XPS). High-resolution transmission electron microscopy (HR-TEM) was used for the investigation of thickness and growth direction of the product layer. TEM lamellae were prepared using the focused ion beam (FIB) technique. Bioactivity of the surface coatings was tested by cultivation of primary human osteoblasts and subsequent analysis of cell morphology, viability, proliferation and differentiation. The results are correlated with the amount of strontium that is released from the coating in biomedical buffer solution, quantified by inductively coupled plasma mass spectrometry (ICP-MS). Results: Dense coatings, consisting of SrOxCly, of more than 100 nm thickness and columnar structure, were prepared. TEM images of cross sections clearly show an incoherent but well-structured interface between coating and substrate without any cracks. Sr2+ is released from the SrOxCly coating into physiological solution as proven by ICP-MS analysis. Cell culture studies showed excellent biocompatibility of the functionalized alloy. Conclusions: Ti-40Nb alloy, a potential orthopedic implant material for osteoporosis patients, could be successfully plasma coated with a dense SrOxCly film. The material performed well in in vitro tests. Nevertheless, the Sr2+ release must be optimized in future work to meet the requirements of an effective drug delivery system.