Osteoporotic fracture treatment has become a skeletal reconstructive challenge due to accelerated bone turnover and impaired bone regeneration potential. Poor osseointegration ability of the osteoporotic bone usually results in implant pull out and failure. Adoption of conventional bone fracture treatment strategies like autografts and allografts have limited applications in such pathological conditions. Hence biomaterials functionalised with therapeutic ions or drugs may be adopted to aid the delivery of therapeutic factors at the defect site to promote bone healing and implant integration, towards functional restoration of the fractured bone. This concise review narrates on improving the osseointegration ability of biomaterials using functional ions like Silica and Strontium. Silica based bone substitutes are known to promote bone healing in non pathological conditions. Further, Strontium based drugs show significant effects in the prevention and treatment of osteoporotic bones. In addition, stem cell therapy has become the focus of orthopaedic research attributed to its ability to restore and accelerate the bone healing process, but the clinical application of stem cells in osteoporotic condition is scarce. Present review suggests a novel strategy of combining the therapeutic potential of functional ions like Silica, Strontium and stem cells within a single implant unit to facilitate osseointegration and osteogenesis, so as to reduce the chances of implant rejection/pull out and encourage osteoporotic bone re-union.
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.
In the present study, we attempt to modify Polycaprolactone (PCL) by blending it with a water soluble polymer Polyethyleneoxide (PEO) having two different molecular weights (Mv ~1,00,000 and 6,00,000) using electrospinning technique. The effect of PEO molecular weight and blend ratio on fiber morphology, porosity, surface wettability, static and dynamic mechanical properties of PCL was investigated. In vitro degradation studies in phosphate buffer saline (PBS) at 37 °C demonstrated formation of pores on fiber surface especially in blend scaffolds with 50:50 ratios. In vitro studies using human osteoblast sarcoma (hOS) cell lines on blend scaffolds showed improved cellular response with good cell adhesion, viability and proliferation. The study revealed that incorporation of PEO on PCL scaffolds complemented the properties of PCL and facilitated fabrication of scaffolds with improved hydrophilicity, mechanical property and tunable degradation profile with better cell viability which makes it an ideal candidate for bone tissue engineering applications.
Bone fractures associated with osteoporosis are a major concern all over the world especially among the elderly population and postmenopausal women. Bisphosphonates (BPs) are widely used clinically for both treatment and prevention of osteoporosis despite their poor oral bioavailability and undesired side effects. Local delivery of BPs from polymeric scaffolds can improve the efficacy and overcome the undesirable side effects associated with oral bisphosphonate therapy. The aim of the present study is to explore the effectiveness of pamidronate (PDS) encapsulated electrospun polycaprolactone/polycaprolactone–polyethyleneglycol–polycaprolactone/nanohydroxyapatite (PCH) scaffolds in healing critical-size calvarial defects in an osteoporotic rat animal model. Prior to implantation studies, the effect of PDS on the fiber architecture, mechanical properties, and in vitro degradation behavior was evaluated. The in vitro release of PDS from PCH scaffolds in phosphate buffer saline (PBS) at 37 °C was monitored for a period of 21 days. An osteoporotic animal model was successfully developed in Wistar rats by bilateral ovariectomy. Results of micro CT (computed tomography) and blood serum analysis confirmed the osteoporotic model induction in rats. Critical-size calvarial defects of 8 mm size were created in osteoporotic rats, and the in vivo osteogenic efficacy of PCH-PDS scaffolds was evaluated by micro CT, histology, and histomorphometry. Micro CT analysis showed improved osseous tissue integration with the use of PDS-loaded PCH scaffolds after 12 week post implantation. Histology, density measurement using micro CT, and histomorphometry further substantiate that PCH-PDS scaffolds have the potential to be used for the repair of osteoporotic bone defects. Our findings revealed that incorporation of PDS onto PCH scaffolds provides a promising biomaterial that could be used for regenerating osteoporosis-related fractures.
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