Novel Aptamer-Functionalized Nanoparticles Enhances Bone Defects Repair by Improving Stem Cell Recruitment

Abstract

The restoration and repair method in clinic of delayed fracture healing and non-union after comminuted fractures are urgently needed to improve the prognosis of patients. Although recruitment of endogenous stem cells has been considered a promising approach in bone defect repair, the current methods are mainly dependent on bio-scaffolds which own disadvantages. Thus, a theranostic platform to overcome these inadequacies is needed indeed. Methods: In this study, using the whole-cell SELEX technique and chemical polymerization, we generated a de novel MSCs aptamer and developed the first, feasible, economical, bio-compatible, and functional MSCs aptamer-directed nanoparticles (Nano-Aptamer Ball, NAB) without complex manufacture to recruit mesenchymal stem cells (MSCs) for bone defect regeneration. Results: In vitro, this MSCs aptamer (termed as HM69) can bind with MSCs with high specificity and Kd of 9.67 nM, while has minimal cross reactivities to other negative cells. Further, aptamer HM69 could capture MSCs with a purity of >89%. In vivo, NAB enhanced MSCs homing in comparison with random DNA or saline, and exhibited superior cartilage restoration when compared with the control group. Principal conclusions: These suggested that HM69 and HM69-functionalized nanoparticles NAB exhibited the ability to recruit MSCs both in vitro and in vivo and achieved a better outcome of bone defect repair in a rat model. The findings demonstrate a promising strategy of using aptamer-functionalized bio-nanoparticles for restoration of bone defects via aptamer-introduced homing of MSCs. Funding Statement: This work was funded by Shaanxi key research and development program (2019SF-207& 2017SF-280); Xi’an Science and Technology program SF1510(4). Declaration of Interests: The authors declare no conflicts of interests. Ethical Approval Statement: Missing.