Effects of locally administered insulin on bone formation in non‐diabetic rats

Abstract

The possibility to control bone formation would be favorable in many areas of medicine, where bone defects is still a major challenge. Insulin has been suggested to exert both systemic and local anabolic effects in bone tissues. This raised the question whether locally administrated insulin could provide new therapeutic strategies for patients with local bone defects and impaired bone healing. The aim of this study was to evaluate bone formation in non-diabetic rats when local insulin is administered. This study differs from previous reports in two aspects: the use of non-diabetic animals and locally administered insulin. Twenty-four implants were inserted into 12 rats-one insulin-coated and one control-in each tibia for four weeks. Interferometry and histomorphometry were used to evaluate the surface topography and bone formation, respectively. Results demonstrated no significant changes in surface topography after insulin immobilization. Histomorphometry revealed significantly more bone around the insulin-coated implants (BA) (p = 0.005) and a similar amount of bone at the implant surface (BIC) (p = 0.117) compared with the controls. It was concluded that locally administered insulin from a titanium implant surface has the potential to increase bone formation not only in diabetic subjects but also in non-diabetic subjects.

Insulin improves osteogenesis of titanium implants under diabetic conditions by inhibiting reactive oxygen species overproduction via the PI3K-Akt pathway

“…Either general insulin administration [7] or local infiltration at the implantebone interface [8] may naturally improve the success of oral implantation in diabetic rats. Malekzadeh et al demonstrated that insulin therapy can neutralize the effects of diabetes on bone healing and can enhance peri-implant bone formation in the disease [9]. Although existing evidence suggests that insulin has potential benefits with respect to osteogenesis under conditions of DM, the underlying mechanisms responsible for this effect are unclear.…”

Insulin released from titanium discs with insulin coatings-Kinetics and biological activity

“…In the authors' previous study, the insulin coated titanium implants demonstrated a larger bone area (BA) around implants, compared to uncoated controls. One hypothesis then was that the significantly higher BA for insulin‐coated implants was due to an insulin release effect, that is, insulin acting on bone cells in the periphery.…”

“…The thickness of the immobilized insulin on the reference Si‐samples ( n = 5) was measured at three different spots on every sample by null ellipsometry, programmed for measurements in air and calculated as reported in our previous study (HeNe laser equipped Auto‐Ell III, Rudolph Research, USA). The immobilized layer thickness was calculated according to the McCrackin evaluation algorithm and converted to an approximate adsorbed amount per unit area by the de Feijter's formula .…”

“…18 A recent in vivo study by the present authors demonstrated increased bone formation around titanium implants when insulin was delivered locally, via immobilization onto the implant surface. 19 The promising initial animal experiments raised the question of whether the improved bone formation around the implants was caused by insulin attached onto the surface, insulin that was released from the surface and acting on a distance, or a combination of both. Other uncertainties were related to the control of insulin release from the surface, and whether released insulin retained its biological activity or was damaged by the immobilization process.…”

Enhanced bone regeneration using an insulin-loaded nano-hydroxyapatite/collagen/PLGA composite scaffold

“…24,25 However, the plasma half-life of insulin is only 5-15 minutes; so, in vivo applications are limited due to short periods of insulin activity. 26,27 In this study, we optimized controlled release of bioactive insulin from nanospheres within the composite scaffold and maintained high insulin concentration at the defect site. To investigate the influence of the composite scaffolds on cell proliferation and osteogenic differentiation, human BMSCs were cultured on the scaffolds.…”