RESUMO
Spinal cord injury (SCI) is a serious clinical disease. Due to the deformability and fragility of the spinal cord, overly rigid hydrogels cannot be used to treat SCI. Hence, we used TPA and Laponite to develop a hydrogel with shear-thinning ability. This hydrogel exhibits good deformation, allowing it to match the physical properties of the spinal cord; additionally, this hydrogel scavenges ROS well, allowing it to inhibit the lipid peroxidation caused by ferroptosis. According to the in vivo studies, the TPA@Laponite hydrogel could synergistically inhibit ferroptosis by improving vascular function and regulating iron metabolism. In addition, dental pulp stem cells (DPSCs) were introduced into the TPA@Laponite hydrogel to regulate the ratios of excitatory and inhibitory synapses. It was shown that this combination biomaterial effectively reduced muscle spasms and promoted recovery from SCI.
RESUMO
The development of 3D printing techniques has provided a promising platform to study tissue engineering and mechanobiology; however, the pursuit of printability limits the possibility of tailoring scaffolds' mechanical properties. The brittleness of those scaffolds also hinders potential clinical application. To overcome these drawbacks, a double-network ink composed of only natural biomaterials is developed. A shear-thinning hydrogel made of silk fibroin (SF) and methacrylated hyaluronic acid (MAHA) presents a high mechanical modulus with a low concentration of macromers. The physical cross-linking due to protein folding further increases the strength of the scaffolds. The proposed SF/MAHA scaffold exhibits a storage modulus 10 times greater than that of methacrylated gelatin scaffold, along with better flexibility and biodegradation. The synergistic effect between fibroin and hyaluronic allows us to tailor the mechanical strength of scaffolds without compromising their printability. The hierarchy porous structure of the SF/MAHA scaffolds offers a better spatial microenvironment for the migration and proliferation of cells compared to gelatin scaffolds. For the first time, this strategy achieves 3D printing of natural biomaterials with controlled mechanical characteristics by manipulating the cross-linking of peptide chains. The design of such ductile scaffolds with hydrolysis resistance provides a new platform for the mechanobiology research. It also shows promise in the tissue engineering of musculoskeletal system where structural strength is needed.
Assuntos
Fibroínas , Materiais Biocompatíveis , Impressão Tridimensional , Engenharia Tecidual , Alicerces TeciduaisRESUMO
Either the natural biodegradation process or the industrial hydrolytic process requires synergistic interactions between various cellulases. However, it is sometimes impeded by low hydrolytic rate of existing cellulases and the lack of accessory enzymes. Herein, the ability of a commercial cellulase (Spezyme CP, from Genencor) to degrade steam explosion-pretreated corn stover was significantly improved. Firstly, a fungal cellulase producer, Aspergillus fumigatus ECU0811, was isolated from hundreds of soil samples. A 96-deep-well microscale-based platform was developed here to reduce the labor-intensive screening work and proved to be consistent with macroscale screening work. After optimization of fermentation, 3% corn cob could induce A. fumigatus ECU0811 to yield the highest cellulase production. Based on the high activities of ß-glucosidase and xylanase by A. fumigatus ECU0811, 0.91 and 125 U/mg protein, respectively, an enzyme cocktail was composed with a fixed dosage of Spezyme CP (CPCel) at 14.2 filter paper units (FPU)/g glucan and varied dosages of A. fumigatus cellulase (AFCel). Consequently, the glucan-to-glucose conversion of corn stover was increased from 25.6% in the presence of CPCel at a dosage of 14.2 FPU/g glucan to 99.5% in the presence of the enzyme cocktail (14.2 FPU CPCel plus 1.21 FPU AFCel per gram of glucan). On the other side, it reduced the total protein amount of CPCel by as much as tenfold, which extremely improved the hydrolytic rate of Spezyme CP and reduced its dosage.