Development of a biostable and biosafe vitreous substitute is highly desirable, but remains a grand challenge. Herein, we propose a novel strategy for constructing a readily administered vitreous substitute based on a thiol-acrylate clickable polyzwitterion macromonomer. A biocompatible multivinyl polycarboxybetaine (PCB-OAA) macromonomer is designed and synthesized, and mixed with dithiothreitol (DTT) via a Michael addition reaction to form a hydrogel in vitreous cavity. This resultant PCB-OAA hydrogel exhibits controllable gelation time, super anti-fouling ability against proteins and cells, excellent biocompatibility, and approximate key parameters to human vitreous body including equilibrium water content, density, optical properties, modulus. Remarkably, outperforming clinically used silicone oil in biocompatibility, this rapidly formed hydrogel in the vitreous cavity of rabbit eyes remains stable in vitreous cavity, showing an appealing ability to prevent significantly inflammatory response, fibrosis and complications such as raised intraocular pressure (IOP), and cataract formation. This zwitterionic polymer hydrogel holds great potential as a vitreous substitute.
Periosteum, a membrane covering the surface of the bone, plays an essential role in maintaining the function of bone tissue-and especially in providing nourishment and vascularization during the bone regeneration process. Currently, most artificial periostea have relatively weak mechanical strength and a rapid degradation rate, and they lack integrated angiogenesis and osteogenesis functions. In this study, a bi-layer, biomimetic, artificial periosteum composed of a methacrylated gelatin-nano-hydroxyapatite (GelMA-nHA) cambium layer and a poly (N-acryloyl 2-lycine) (PACG) -GelMA-Mg 2+ fibrous layer was fabricated via 3D printing. The GelMA-nHA layer is shown to undertake the function of improving osteogenic differentiation of rat bone marrow mesenchymal stem cells with the sustainable release of Ca 2+ from nHA nanoparticles. The hydrogen-bonding-strengthened P(ACG-GelMA-L)-Mg 2+ hydrogel layer serves to protect the inner defect site and prolong degradation time (60 days) to match new bone regeneration. Furthermore, the released magnesium ion exhibits a prominent effect in regulating the polarization phenotype of macrophage cells into the M2 phenotype and thus promotes the angiogenesis of the human umbilical vein endothelial cells in vitro. This bi-layer artificial periosteum was implanted into a critical-sized cranial bone defect in rats, and the 12-week post-operative outcomes demonstrate optimal new bone regeneration.
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