Nanohydroxyapatite Based Ceramic Carrier Promotes Bone Formation in a Femoral Neck Canal Defect in Osteoporotic Rats

Abstract

Hip fractures are among the most common types of fracture risks in old age osteoporotic patients that often end up with immobile disabilities. Weak bones due to loss of mineral content along with an increase in the porosity of the femur neck canal in osteoporosis reduce the mechanical properties of the bone and predispose the patients to fractures. In this study, we have used calcium sulfate/nanohydroxyapatite based nanocement (NC) as carrier of recombinant human bone morphogenetic protein-2 (BMP-2), zoledronate (ZA), and bone marrow mesenchymal stromal cells (MSCs) derived exosomes (EXO) to enhance bone formation and defect healing in a femur neck canal defect model in osteoporotic rats. A cylindrical defect in the femur neck canal with dimensions of 1 mm (diameter) × 8 mm (length) starting from the lateral cortex toward the apex of the femur head was developed. The defect was impacted using NC alone or functionalized as (a) NC + ZA (systemic), (b) NC + ZA (local), (c) NC + EXO + ZA, and (d) NC + BMP + ZA to evaluate bone formation by ex vivo micro-computed tomography (micro-CT) and histological analysis 16 weeks postsurgery. Moreover, the femurs (both defect and contralateral leg) were subjected to biomechanical analysis to assess the effect of treatments on compressive mechanical properties of the bones. The treatment groups (NC + ZA (L), NC + BMP + ZA, and NC + EXO + ZA) showed enhanced bone formation with complete healing of the defect. No differences in the mechanical properties of both the defect and contralateral across the leg were observed among the groups. However, a trend was observed where NC + BMP + ZA showed enhanced biomechanical strength in the defect leg. This suggests that NC could act as a potent carrier of bioactive molecules to reduce the risks of hip fractures in osteoporotic animals. This type of treatment can be given to patients who are at higher risk of osteoporosis mediated femur neck fracture as a preventive measure or for enhanced healing in already compromised situations. Moreover, this study provided a proof of concept regarding the use of exosomes in bone regeneration therapy, which might be used as a booster dose that will eventually reduce the dosage of BMP and hence circumvent the limitations associated with the use of BMP.

A biphasic nanohydroxyapatite/calcium sulphate carrier containing Rifampicin and Isoniazid for local delivery gives sustained and effective antibiotic release and prevents biofilm formation

“…In the current study, we have used a ceramic based hydroxyapatite bone substitute as a carrier of two first line anti-tuberculosis drugs, Rifampicin and Isoniazid. The potency of a sulphate hydroxyapatite carrier for bioactive molecules to promote bone healing was established in earlier studies 22 , 26 , 39 – 41 . Apart from achieving long term sustained release of drugs, it can act as a bone filler material to fill the dead space at the debrided site.…”

“…The aim of this study was to use a biphasic CSH/nHAP based nanocement (NC) carrier for local delivery of two first line ATDs (RFP and INH) to achieve the long-term sustained and controlled release. Similar carriers have been previously used as a carrier for bone morphogenetic proteins (BMP) and zoledronic acid (ZA) to promote either the fracture healing 22 – 24 or enhance the bone mineralization in osteoporotic rats 25 , 26 . To our knowledge, this study is the first to describe the release profile of tuberculosis drugs in a ceramic carrier.…”

Porous Zirconia/Magnesia Ceramics Support Osteogenic Potential In Vitro

“…The results from the ALP activity, calcium and collagen production clearly demonstrated that the zirconia/magnesia ceramics possess robust osteoinductive capacity, and thus present great potential for bone tissue engineering applications. In addition, ceramic materials can be used as carriers to deliver cytokines such as bone morphogenetic pro-teins [36], specific osteogenic growth factors that enhance bone formation in vitro [37] and in vivo [33], as well as plasmids for the transfection of bone-forming cells [38], or cement formulations [39] leading to enhanced osteogenic responses. Magnesium-based orthopaedic implants such as pins, plates and screws have been extensively investigated in both small and large animal models, in physiological and osteoporotic models, mainly to observe the degradation pattern of Mg-based implants and the response of peri-implant bone tissue [40].…”

The Delivery of Extracellular Vesicles Loaded in Biomaterial Scaffolds for Bone Regeneration

“…However, the effect of exosomes on enhancing osteoblast differentiation was not observed in a subsequent in vitro study. Qayoom et al (2019) also proposed the role of EVs in a femur neck canal defect model in osteoporotic rats as a biological carrier facilitating bone formation and controlling the dosage of BMP. They used nano cements to deliver BMPs, exosomes, and bisphosphonates, which improved biomechanical strength in the defect.…”