Osteogenic efficacy of strontium hydroxyapatite micro-granules in osteoporotic rat model

Abstract

Excessive demineralization in osteoporotic bones impairs its self-regeneration potential following a defect/fracture and is of great concern among the aged population. In this context, implants with inherent osteogenic ability loaded with therapeutic ions like Strontium (Sr) may bring forth promising outcomes. Micro-granular Strontium incorporated Hydroxyapatite scaffolds have been synthesized and in vivo osteogenic efficacy was evaluated in a long-term osteoporosis-induced aged (LOA) rat model. Micro-granules with improved surface area are anticipated to resorb faster and together with the inherent bioactive properties of Hydroxyapatite with the leaching of Strontium ions from the scaffold, osteoporotic bone healing may be promoted. Long-term osteoporosis-induced aged rat model was chosen to extrapolate the results to clinical osteoporotic condition in the aged. Micro-granular 10% Strontium incorporated Hydroxyapatite synthesized by wet precipitation method exhibited increased in vitro dissolution rate and inductively coupled plasma studies confirmed Strontium ion release of 0.01 mM, proving its therapeutic potential for osteoporotic applications. Wistar rats were induced to long-term osteoporosis-induced aged model by ovariectomy along with a prolonged induction period of 10 months. Thereafter, osteogenic efficacy of Strontium incorporated Hydroxyapatite micro-granules was evaluated in femoral bone defects in the long-term osteoporosis-induced aged model. Post eight weeks of implantation in vivo regeneration efficacy ratio was highest in the Strontium incorporated Hydroxyapatite implanted group (0.92 ± 0.04) compared to sham and Hydroxyapatite implanted group. Micro CT evaluation further substantiated the improved osteointegration of Strontium incorporated Hydroxyapatite implants from the density histograms. Thus, the therapeutical potential of micro-granular Strontium incorporated Hydroxyapatite scaffolds becomes relevant, especially as bone void fillers in osteoporotic cases of tumor resection or trauma.

Innovative Biomaterials in Bone Tissue Engineering

“…The obtained microgranules were characterized using XRD and SEM methods and were further implanted in nine osteoporotic rats, being evaluated by Micro-CT . After explantation, the newly bone formed in presence of 10%SrHA microgranules and presented a density comparable to the host native tissue [44]. The explants with HA microgranules exhibited a slight decrease in bone density, fact supporting the idea that such composition may be used in the treatment of the osteoporotic bones [44].…”

“…In vivo studies were conducted by Chandran et al, in two different species: osteoporotic sheep and rat models. [44][45]. First, they fabricated microgranules of 10% SrHA (with the chemical formula Ca 9 Sr 1 (PO 4 ) 6 (OH) 2 ) and simple HA (used as control), in order to assess the osteogenic potential and the osteointegration speed.…”

Functionalization of Ceramic Coatings for Enhancing Integration in Osteoporotic Bone: A Systematic Review

“…Results obtained from the evaluation of osteogenic potential of Sr incorporated HA micro-granules are in line with these evidences. Chandran et al demonstrated in a long-term OP-induced aged model that the combination of Sr and highly porous HA promotes complete bone healing, showing a regeneration efficacy higher than the HA group, also confirmed by microCT evaluation of the trabecular bone status [37].…”

Ovariectomised and Long Term Induced (Oli) Rat Model for Preclinical Assessment of Osteoporotic Therapeutics.

“…Impaired proliferation and differentiation potential of resident mesenchymal stem cells and induction factors have been reported to delay bone healing 29 . In short term-induced models, delay in fracture healing is attributed to the accelerated resorption by osteoclast cells resulting in bone loss, but these models lack the reduction in osteogenic capacity of the bone-forming cells 30 . Conversely, in our study impaired osteogenic potential was evident in the long term induced osteoporotic model by 8 weeks, whereas the Control rats exhibited a complete bridging of the defect.…”