Noninvasive monitoring of bone regeneration using NaYF_4: Yb~(3+) , Er~(3+) upconversion hollow microtubes supporting PLGA-PEG-PLGA hydrogel

摘要

In this work, a novel injectable luminescent hydrogel composite composed of poly(c-lactide-co-glycolide)-poly (ethylene glycol)-poly(L-lactide-co-glycolide) (PLGA-PEG-PLGA) triblock copolymer and NaYF4: Yb3+, Er3+ hollow microtubes was successfully prepared for noninvasive monitoring of bone regeneration. The incorporation of NaYF4: Yb3+, Er3+ hollow microtubes into the matrix of PLGA-PEG-PLGA resulted in the hydrogel with much rougher surface, enhanced mechanical strength, and bright upconversion luminescence. The in vitro experiments showed that the composite hydrogel possessed ideal sustained drug release property for protein drugs. Besides, it also exhibited good cellular compatibility and cell adhesion property for bone marrow mesenchymal stem cells. After loading of recombinant human bone morphogenetic protein 2 (osteogenic induction factor), the composite hydrogel was definitively implanted into the tibial defect of rats to evaluate the bone regeneration. The degradation of the composite hydrogel scaffolds and the bone defect repairing in vivo was noninvasive monitored by real-time upconversion luminescent imaging and X-ray computed tomography. The results showed that the composite hydrogel scaffold was completely degraded after 4 weeks. Moreover, a successful tibial defect repairing was realized after 6 weeks of bone regeneration. The hematoxylin-eosin staining experiments showed that the implantation and degradation of the composite hydrogel have no significant damages to the organs of heart, liver, spleen, lung and kidney during the therapeutic process, indicating its good biological safety. Our strategy provides a safety way for the noninvasive monitoring of bone regeneration, which is believed to have great potential clinical uses.