PLGA Containing Human Adipose-Derived Stem Cell-Derived Extracellular Vesicles Accelerates the Repair of Alveolar Bone Defects via Transfer of CGRP

Abstract

Calcitonin gene-related peptide (CGRP) is an important neuropeptide expressed in the nerve fibers during bone repair. Here, we aimed to pinpoint the role of CGRP in the osteogenic differentiation property of human periodontal ligament stem cells (hPDLSCs) and the resultant repair of alveolar bone defect. The key factor related to the osteogenic differentiation of hPDLSCs was retrieved from the GEO database. After extraction from hADSCs (hADSC-EVs) and identification, EVs were subjected to coculture with hPDLSCs, in which the expression patterns of CGRP and osteogenic differentiation marker proteins (ALP, RUNX2, and OCN), as well as ALP activity, were detected. A novel cell-free tissue-engineered bone (TEB) comprised of PLGA/pDA and hADSC-EVs was implanted into the rats with alveolar bone defects to evaluate the repair of alveolar bone defects. CGRP was enriched in hADSC-EVs. hADSCs delivered CGRP to hPDLSCs through EVs, thereby promoting the osteogenic differentiation potential of hPDLSCs. The PLGA/pDA-EV scaffold released EVs slowly, and its implantation into the rat alveolar bone defect area significantly induced bone defect repair, which was reversed by further knockdown of CGRP. In conclusion, our newly discovered cell-free system consisted of hADSC-EVs, and PLGA/pDA scaffold shows promising function in repairing alveolar bone defects.

Superoxide dismutase 2 scavenges ROS to promote osteogenic differentiation of human periodontal ligament stem cells by regulating Smad3 in alveolar bone‐defective rats

“…We successfully constructed a rat alveolar bone defect model referring to the research of Yang et al 24 . As shown in Figure 3A, 7‐week‐old male Sprague–Dawley (SD) rats (weight range 250 ± 20 g) were provided by the Animal Center of Southern Medical University.…”

“…We successfully constructed a rat alveolar bone defect model referring to the research of Yang et al 24 As shown in Figure 3A, 7-week-old male Sprague-Dawley (SD) rats (weight range 250 ± 20 g) were provided by the Animal Center of Southern Medical University. The animals were housed under specific pathogen-free conditions (22 ± 2 • C; 55% ± 10% humidity) under a 12/12 h light-dark cycle.…”

Nerves within bone and their application in tissue engineering of bone regeneration

“…Combining CGRP directly with new biomaterials is another strategy, which was adopted by only a few studies. Yang et al ( 21 ) constructed PLGA/Pda-EV scaffold which slowly delivered CGRP and demonstrate its effect on accelerating bone repair. For such studies, the sustained release and half-life of CGRP and specific mechanisms of interaction between CGRP and bone formation need to be further elucidated.…”

The role of extracellular vesicles in periodontitis: pathogenesis, diagnosis, and therapy

“…found that the injection of adipose-derived mesenchymal stem cells (ADSCs) exosomes suspension can be used as an auxiliary tool to promote periodontal regeneration, specifically periodontal fibers, blood vessels, and alveolar bone. The polydopamine-coated poly(lactic-co-glycolic acid) (PLGA/pDA) scaffold combined with ADSCs-EVs significantly induced the alveolar bone defect repair in the rat model ( 204 ). The ADSCs exosomes immobilized on the PLGA/pDA scaffolds promote the repair of critical-size skull defects in rats by stimulating osteogenesis and promoting BMSCs migration and homing ( 205 ).…”