Journal
ACS APPLIED MATERIALS & INTERFACES
Volume 12, Issue 34, Pages 37873-37884Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acsami.0c09004
Keywords
injectability; strontium; dendrimer; osteoporosis; biphasic calcium phosphate
Funding
- National Natural Science Foundation of China [81971755]
- PNR Aging Program (2012-2018)
- Sichuan Science and Technology Program [2020YFS0038]
- Sichuan Science and Technology Innovation Team of China [2019JDTD0008]
- Young Elite Scientist Sponsorship Program by CAST [2019QNRC001]
- Fundamental Research Funds for the Central Universities
- Guike [AA17204085-2]
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Injectable biphasic calcium phosphates have been proposed as a solution in the treatment of a range of clinical applications including as fillers in the augmentation of osteoporotic bone. To date, various biodegradable natural or synthetic organics have been used as a polymer component of bone materials to increase their cohesiveness. Herein, a novel bone material was developed combining osteoconductive biphasic calcium phosphate (BCP) nanoparticles with phosphoserine-tethered generation 3 poly(epsilon-lysine) dendron (G3-K PS), a class of hyperbranched peptides previously shown to induce biomineralization and stem cell osteogenic differentiation. Strontium was also incorporated into the BCP nanocrystals (SrBCP) to prevent bone resorption. Within 24 h, an antiwashout behavior was observed in G3-K PS-integrated pure BCP group (BCPG3). Moreover, both in vitro tests by relevant cell phenotypes and an in vivo tissue regeneration study by an osteoporotic animal bone implantation showed that the integration of G3-K PS would downregulate Cxcl9 gene and protein expressions, thus enhancing bone regeneration measured as bone mineral density, new bone volume ratio, and trabecular microarchitectural parameters. However, no synergistic effect was found when Sr was incorporated into the BCPG3 bone pastes. Notably, results indicated a concomitant reduction of bone regeneration potential assessed as reduced Runx2 and PINP expression when bone resorptive RANKL and CTX-I levels were reduced by Sr supplementation. Altogether, the results suggest the potential of injectable BCPG3 bone materials in the treatment of osteoporotic bone defects.
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