Zhencheng Liao,Yiming Niu,Zhenzhen Wang,Jiaxi Chen,Xiaoyan Sun,Lei Dong,Chunming Wang
3D printing enables the customized design of implant structures for accurately regulating host responses. However, polysaccharides, as a major biomaterial category with versatile immune activities, are typically “non-printable” due to the collapse of their filaments extruded during printing. This challenge renders their potential as immunomodulatory scaffolds underexploited. Here, inspired by the quench hardening in metal processing, a nonsolvent quenching (NSQ) strategy is innovatively designed for the 3D printing of polysaccharides. Through rapid solvent exchanging, NSQ instantly induces surface hardening to strengthen the polysaccharide filaments upon extrusion, requiring neither chemical modification nor physical blending that alters the material properties. Tested with five polysaccharides with varying physicochemical properties, NSQ prints predesigned structures at organ-relevant scales and a long shelf-life over 3 months. Glucomannan scaffolds, fabricated via NSQ with different grid spacings (1.5 and 2.5 cm), induce distinct host responses upon murine subcutaneous implantation—from specific carbohydrate receptor activation to differential immunocytes accumulation and tissue matrix remodeling—as mechanistically validated in wild-type and Tlr2 −/− knockout mice. Overall, NSQ as a facile and generic strategy is demonstrated to fabricate polysaccharide scaffolds with improved shape fidelity, thereby potentially unmasking their accurate immunomodulatory activities for future biomaterials design.
Min He,Xinhui Gao,Yadi Fan,Li Xie,Mo Yang,Weidong Tian
Instead of directly stimulating osteogenesis, endowing an implant surface with a favourable osteoimmunomodulatory (OIM) function has emerged as a new effective strategy to enhance osteointegration. Though metal-phenolic coatings have demonstrated to possess an immunomodulatory function, their potential application in manipulating an osteoimmune response has not been well explored. Herein, in order to develop a simple, rapid and universal coating method to impart excellent OIM to hard tissue implants, tannic acid (TA) and Mg2+ were selected to form a coating on Ti plate based on metal-phenolic chemistry. Besides its virtues of simplicity, ultrafastness, low-cost, and versatility, another merit for the coating method is that it can easily combine the unique functions of metal ions and phenolic ligands. The chelated Mg2+ can not only activate macrophage polarization towards the anti-inflammatory phenotype but also directly stimulate the osteogenic differentiation of bone marrow-derived stem cells (BMSCs). TA motifs rendered the coating with an excellent reactive oxygen species (ROS) scavenging capacity. TA and Mg2+ showed synergistic effects on regulating macrophage biological behaviour, suppressing its polarization towards the M1 phenotype, and promoting its polarization towards the M2 phenotype. In vivo histological analysis also demonstrated that the TA/Mg2+ coating could effectively inhibit the host response. Finally, the formed osteoimmune environment obviously enhanced the osteogenic differentiation of BMSCs. The above results demonstrated that the designed TA/Mg2+ coating not only possessed the function of directly stimulating osteogenesis but also the function of manipulating OIM to a desired one. Hence, it has great potential to be applied on advanced hard tissue implants to enhance osteointegration.