Three-dimensional (3D) bioprinting of medium toughened dipeptide hydrogel scaffolds with Hofmeister effect.

Short peptide self-assembled hydrogels as 3D bioprinting inks show excellent biocompatibility and diverse functional expansion, and have broad application prospects in cell culture and tissue engineering. However, the preparation of biological hydrogel inks with adjustable mechanical strength and controllable degradation for 3D bioprinting still faces big challenges. Herein, we develop dipeptide bio-inks that can be gelled in-situ based on Hofmeister sequence, and prepare hydrogel scaffold by using a layer-by-layer 3D printing strategy. Excitingly, after the introduction of Dulbecco's Modified Eagle's medium (DMEM), which is necessary for cell culture, the hydrogel scaffolds show an excellent toughening effect, which matches the needs of cell culture. It's notable that in the whole process of preparation and 3D printing of hydrogel scaffolds, no cross-linking agent, ultraviolet (UV), heating or other exogenous factors are involved, ensuring high biosafety and biocompatibility. After two weeks of 3D culture, millimeter-sized cell spheres are obtained. This work provides an opportunity for the development of short peptide hydrogel bioinks without exogenous factors in 3D printing, tissue engineering, tumor simulant reconstruction and other biomedical fields.

Surface Self-Assembly of Dipeptides on Porous CaCO3 Particles Promoting Cell Internalization.

The self-assembling behavior of peptides and derivatives is crucial in the natural process to construct various architectures and achieve specific functions. However, the surface or interfacial self-assembly, in particular, on the surface of micro- or nanoparticles is even less systematically investigated. Here, uniform porous CaCO3 microparticles were prepared with different charged, hydrophobic and hydrophilic surfaces to assess the self-assembling behavior of dipeptides composed of various sequences. Experimental results indicate that dipeptides with a negative charge in an aqueous solution preferred to self-assemble on the hydrophobic and positively charged surface of CaCO3 particles, which can be ascribed to the electrostatic and hydrophobic interaction between dipeptides and CaCO3 particles. Meanwhile, the Log p (lipid-water partition coefficient) of dipeptides has a significant effect on the self-assembling behavior of dipeptides on the surface of porous CaCO3; dipeptides with high Log p preferred to self-assemble on the surface of CaCO3 particles, resulting in the improved cell internalization efficiency of particles with low cytotoxicity. After loading with a model drug (doxorubicin), the particles show obvious antitumor activity in animal experiments and can reduce Dox side effects effectively.

In situ synthesis of superorganism-like Au NPs within microgels with ultra-wide absorption in visible and near-infrared regions for combined cancer therapy.

The whole is a collection of parts and fulfills specific functions that the parts do not have. In this work, 50 nm Au NPs were in situ synthesized and close packed into a superorganism-like superstructure by means of microgel 3D networks. The combined microgel is endowed with ultra-wide absorption in visible and near-infrared regions between 500 and 1100 nm in spite of Au NPs not having this property. The strong collective plasmon coupling between neighboring Au NPs induces high photothermal conversion efficiency of the microgel system under irradiation at various laser wavelengths. Due to the good loading capability, microgels with nanocomposites can also load photosensitive drugs simultaneously and be used for combined cancer treatments of photothermal therapy and photodynamic therapy.

Enhanced neuroprotection and improved motor function in traumatized rat spinal cords by rAAV2-mediated glial-derived neurotrophic factor combined with early rehabilitation training.

BACKGROUND: Spinal cord injury (SCI) is a serious neurological injury that often leads to permanent disabilities for the victims. The aim of this study was to determine the effects of glial-derived neurotrophic factor (GDNF) mediated by recombinant adeno-associated virus type 2 (rAAV2) alone or in combination with early rehabilitation training on SCI. METHODS: SCI was induced on the T8-9 segments of the spinal cord by laminectomy in adult male Sprague-Dawley rats. Then besides the sham operation group, the SCI rats were randomly divided into four groups: natural healing group, gene therapy group, rehabilitation training group, and combination therapy group (gene therapy in combination with rehabilitation training). Motor dysfunction, protein expression of GDNF, edema formation, and cell injury were examined 7, 14, and 21 days after trauma. RESULTS: The topical application of rAAV-GDNF-GFP resulted in strong expression of GDNF, especially after the 14th day, and could protect the motor neuron cells. Early rehabilitative treatment resulted in significantly improved motor function, reduced edema formation, and protected the cells from injury, especially after the 7th and 14th days, and increased the GDNF expression in the damaged area, which was most evident after Day 14. The combined application of GDNF and early rehabilitative treatment after SCI resulted in a significant reduction in spinal cord pathology and motor dysfunction after the 7th and 14th days. CONCLUSION: These observations suggest that rAAV2 gene therapy in combination with rehabilitation therapy has potential clinical value for the treatment of SCI.