Pamidronate-Encapsulated Electrospun Polycaprolactone-Based Composite Scaffolds for Osteoporotic Bone Defect Repair

Abstract

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.

Nano-Hydroxyapatite Composite Scaffolds Loaded with Bioactive Factors and Drugs for Bone Tissue Engineering

“…Rajan et al used electrostatic spinning technology to load pamidronate into polycaprolac-tone/polycaprolactone-polyethyleneglycol-polycaprolactone/n-HAp (PCH) scaffold, and the study confirmed that PDS in the composite scaffolds was well-released in phosphate buffer. The PCH scaffolds incorporating 3 wt % PDS can effectively promote the bone healing of calvarial defects in osteoporotic rats [ 166 ]. Alendronate is a nitrogen-containing bisphosphonate.…”

Modified Poly(ε-caprolactone) with Tunable Degradability and Improved Biofunctionality for Regenerative Medicine

“…Poly­(ε-caprolactone) is widely applied in long-term surgical implants − and slow-releasing drug-delivery systems − due to its biocompatibility, biodegradability, and suitable mechanical properties. In tissue engineering, PCL has been studied for applications that require slowly degrading materials, for example, guided bone regeneration − and vascular grafts. − Researchers have also explored ways to modify PCL to increase its degradation rate. , One approach is to make copolymers or to blend PCL with other polymers, such as polylactic acid, − poly­( N -(2-hydroxypropyl)­methacrylamide), alginate, , starch, , and zein . However, blending polymers can result in phase separation, degrading the mechanical properties of the resulting material. , In addition, blending may lead to loss of the desired characteristics of the original system, such as solubility, biocompatibility, mechanical properties, etc.…”

UV-Crosslinked Electrospun Zein/PEO Fibroporous Membranes for Wound Dressing

“…The production of fibroporous membranes via the electrospinning technique has turned into an area of extensive research with the potential of fabricating commercial products on a large scale . The large surface area-to-volume ratio of the electrospun membrane is a favorable attribute for drug delivery applications, tissue repair, biological dressing, enzyme immobilization, etc. , The versatility of the technique lies in the fact that different processing modifications are possible with it including multiple fluid processing like co-axial electrospinning, side-by-side electrospinning, tri-axial electrospinning, , etc. Recently, fabrication of fibrous membranes with “smart” properties is gaining much attention also .…”