Delivery of antagomiR204-conjugated gold nanoparticles from PLGA sheets and its implication in promoting osseointegration of titanium implant in type 2 diabetes mellitus

Abstract

Impaired osseointegration of the implant remains the big hurdle for dental implant therapy in diabetic patients. In this study, the authors first identified that miR204 was strikingly highly expressed in the bone mesenchymal stem cells (BMSCs) of diabetic rats. Forced expression of miR204 repressed the osteogenic potential of BMSCs, while inhibition of miR204 significantly increased the osteogenic capacity. Moreover, the miR204 inhibitor was conjugated with gold nanoparticles (AuNP-antagomiR204) and dispersed them in the poly(lactic-co-glycolic acid) (PLGA) solution. The AuNP-antagomiR204 containing PLGA solution was applied for coating the surface of titanium implant. Electron microscope revealed that an ultrathin sheet was formed on the surface of the implant, and the AuNPs were evenly dispersed in the coated PLGA sheet. Cellular experiments revealed that these encapsulated AuNP-antagomiR204 were able to be released from the PLGA sheet and uptaken by adherent BMSCs. In vivo animal study further confirmed that the AuNP-antagomiR204 released from PLGA sheet promoted osseointegration, as revealed by microcomputerized tomography (microCT) reconstruction and histological assay. Taken together, this study established that miR204 misexpression accounted for the deficient osseointegation in diabetes mellitus, while PLGA sheets aided the release of AuNP-antagomiR204, which would be a promising strategy for titanium implant surface functionalization toward better osseointegration.

Molecular mechanism of diabetic cardiomyopathy and modulation of microRNA function by synthetic oligonucleotides

“…In vitro delivery of anti-miR-155 with PMO and PNA modification demonstrated significant knockdown of miR-115 [ 221 ] whereas, in vivo study further demonstrated that PLGA nanoparticles encapsulating anti-miR-155 PNA could accumulate in the pre-B cell tumours through enhanced permeability and retention effect [ 222 ]. On other hand, Liu et al demonstrated that anti-miR-204 encapsulated with PLGA nanoparticles promotes osteogenesis in type 2 diabetes [ 223 ]. To date only limited reports available for using nanoparticle-mediated delivery of miRs to treat cardiovascular disease.…”

Bone Marrow Mesenchymal Stromal Cells (BMMSCs) Augment Osteointegration of Dental Implants in Type 1 Diabetic Rabbits: An X-Ray Micro-Computed Tomographic Evaluation

“…Increased levels of tissue necrotic factor (TNF) and reduction in bone morphogenetic protein-6 (BMP-6) are some of the reported mechanisms that could be implicated for delayed or failed osseointegration in diabetic cases [45,46]. Coating of polylactic-co-glycolic acid (PGLA) containing miR204 inhibitors and gold nanoparticles on the implant to overcome such attenuation has been reported to enhance implant homing [47]. However, the current study implies that the localized administration of inductive BMMSCs from a healthy rabbit can enhance osseointegration in diabetic conditions.…”

Recent Evidence on Dental Implant in Type 2 Diabetes Mellitus Patients

“…Patients suffering from DM have increased the frequency of tooth loss due to periodontitis, impaired response to infection, and delayed wound healing.Successful osseointegration of the dental implant in DM patients is a challenge and matter research since long. 1,2 Al Zahrani and Al Mutairi 1,3 evaluated stability and peri-implant bone loss (PIBL) around non-submerged and submerged dental implants in patients with and without T2DM. Increased PIBL was found around non-submerged implant-supported restorations in T2DM patients.…”

“…In the case of T2DM patients, for early intervention of postextraction, alveolar ridge preservation surgery is recommended. 9 Liu et al 2 found that miR204 misexpression accounted for the deficient osseointegration in DM. In T2DM patients, better osseointegration can be obtained by poly (lactic-co-glycolic acid) (PLGA) sheets which aid in the release of gold nanoparticles (AuNP-antagomiR204), and helps in the functionalization of the titanium implant surface and overcome the poor bone-implant contact in T2DM.…”

“…In T2DM patients, better osseointegration can be obtained by poly (lactic-co-glycolic acid) (PLGA) sheets which aid in the release of gold nanoparticles (AuNP-antagomiR204), and helps in the functionalization of the titanium implant surface and overcome the poor bone-implant contact in T2DM. 2 Recent researches had provided promising results, and it is recommended that dental implants can be placed in patients if glycemic levels are under control in T2DM patients. Delayed implant insertion protocol must be followed in T2DM patients and glycemic levels must be controlled with strict dietary control and regular exercise along with antihyperglycemic medications.…”