Uniform-sized insulin-loaded PLGA microspheres for improved early-stage peri-implant bone regeneration

Abstract

Poor initial stability at the first four weeks after surgery is becoming the major causes for metal implant failure. Previous attempts neglected the control release of insulin for the bone regeneration among nondiabetic subjects. The major reason may lie in the adverse effects, such as attenuated bone formation, hypoglycemia or hyperinsulinemia, that caused by the excessive insulin. Thus, spatiotemporal release of insulin may serve as the promising strategy. To address this, through solvent extraction (EMS), solvent evaporation (SMS) and cosolvent methods (CMS), we prepared three types of PLGA microspheres with various internal structures, but similar size distribution. The effects of the preparation methods on the properties of the microspheres, such as their release behavior, degradation of molecular weight, and structural evolution, were investigated. Human bone marrow mesenchymal stromal cells (BMSCs) and rabbit implant models were used to test the bioactivity of the microspheres in vitro and in vivo, respectively. The result demonstrated that these three preparation methods did not influence the polymer degradation but instead affected the internal structural evolution, which plays a crucial role in the release behavior, osteogenesis and peri-implant bone regeneration. Compared with EMS and CMS microspheres, SMS microspheres exhibited a relatively steady release rate in the first four weeks, which evidently stimulated the osteogenic differentiation of the stem cells and peri-implant bone regeneration. Meanwhile, SMS microspheres significantly enhanced the stability of the implant at Week 4, which is promising to reduce early failure rate of the implant without inducing adverse effects on the serum biochemical indices.

A Multi‐Functional Implant Induces Bone Formation in a Diabetic Model

“…In addition, the blood glucose levels of ZDF rats were checked pre‐operatively and at the time of euthanasia (7, 14, 21, and 28 days) and showed no significant difference in blood glucose levels in rats receiving either treatment, and were consistent with previous reports (Figure 2c). [ 46 ] Thus, the biocompatibility of the implants was confirmed as all rats remained healthy for the entire period of the study and showed no noticeable signs of toxicity or other adverse effects.…”

“…[ 55 ] Looking at the ZL rat groups, the general trend was that the addition of VD3 or INS MPs improved bone generation which is consistent with previously reported data. [ 46,56 ] Wang et al. coated similarly prepared INS MPs onto titanium screws in a rabbit mandibular defect model and found increased bone formation and pull out strength when INS was released steadily at the defect site.…”

“…coated similarly prepared INS MPs onto titanium screws in a rabbit mandibular defect model and found increased bone formation and pull out strength when INS was released steadily at the defect site. [ 46 ] VD3, as previously mentioned, has also been used for bone tissue regeneration. For example, VD3 in a Pluronic coating on a titanium scaffold significantly increased bone ingrowth in a rabbit femur model.…”

Local delivery of insulin/IGF-1 for bone regeneration: carriers, strategies, and effects

“…The degradation rate of PLGA is mainly dependent on the ratio of glycolic acid to lactic acid monomer [45]. To obtain more detailed information on accurate regulation of the release profile of insulin-loaded particles, three kinds of uniform-sized insulin microspheres were prepared using the solvent extraction, solvent evaporation and cosolvent methods, respectively [46]. It was found that insulin-loaded microspheres prepared by the solvent evaporation method exhibited a relatively steady release rate during the first four weeks, which significantly stimulated the osteogenic differentiation of the stem cells and peri-implant bone regeneration.…”

Clinical and Radiographic Variables Around Implant With Simultaneous Graft Among Type 2 Diabetic Patients Treated With Different Hypoglycemic Medications: A Retrospective Study.

“…This bene cial effect might improve the outcome of dental implants. It was reported that local application of insulin could promote osseointegration in T2DM rats 14 . Glucagon-like peptide-1 (GLP-1) drugs also have the potential to promote osseointegration around implants 15 .…”