Extensive early mineralization of pre-osteoblasts, inhibition of osteoclastogenesis and faster peri-implant bone healing in osteoporotic rat model: principle effectiveness of bone-specific delivery of Tibolone as evaluated in vitro and in vivo

Abstract

Hydrophobic drug molecules pose a significant challenge in immobilization on super-hydrophobic metallic surfaces like conventional titanium implants. Pre-coating surface modifications may yield a better platform with improved wettability for such purposes. Such modifications, as depicted in this study, were hypothesized to provide the requisite roughness to assist deposition of polymers like silk fibroin (SF) as a drug-binding matrix in addition to significant improvement in early protein adsorption, which facilitates faster cellular adhesion and proliferation. A silk-based localized drug delivery module was developed on the titanium surface and tested for its surface roughness, wettability, biocompatibility and in vitro differentiation potential of cells cultured on the coated metallic surfaces with/without external supplementation of the active metabolite of Tibolone. Conditioning of the matrix-coated implants with osteogenic as well as osteoclastogenic media supplemented with Tibolone stimulated the expression of early osteogenic gene and calcium deposition in the extracellular matrix. Significant inhibition in resorptive activity was also observed in the presence of the drug. To assess the efficacy of localized delivery of Tibolone via topographically modified titanium implants for inducing early peri-implant bone formation, osteoporosis was artificially induced in rats subjected to bilateral ovariectomy and implants were placed thereafter. Bone-specific release of Tibolone through the biomimetic matrix in osteoporotic rats collectively indicated significant improvement in peri-implant bone growth after 2 and 4 weeks (p < 0.05 compared to dummy-coated implants). These findings demonstrate for the first time that Tibolone released from SF matrix-coated implants can accelerate the biological stability of bone fixtures.

Electrospun Silk Fibroin/kappa-Carrageenan Hybrid Nanofibers with Enhanced Osteogenic Properties for Bone Regeneration Applications

“…ALP is a biomarker of osteogenesis that appears in the early stage of osteo differentiation and is linked to osteoblast cell mineralization activity [50,51]. Calcific occurs through the hydrolysis of phosphate esters by ALP, which leads to the accum tion of inorganic phosphates and Ca 2+ and thereby increasing ECM mineralization ALP enzyme is a transcription factor that activates the cell differentiation factors, as as playing a role in message transmission and osteoblast differentiation [52].…”

“…ALP is a biomarker of osteogenesis that appears in the early stage of osteogenic differentiation and is linked to osteoblast cell mineralization activity [50,51]. Calcification occurs through the hydrolysis of phosphate esters by ALP, which leads to the accumulation of inorganic phosphates and Ca 2+ and thereby increasing ECM mineralization.…”

Titanium‐Based Nanoarchitectures for Sonodynamic Therapy‐Involved Multimodal Treatments

“…In addition, the use of other formulations and devices, including hydrogels, implants, microneedle patches, sprays, and wearable devices can pave such a route. [ 182,183 ] However, Ti‐based multifunctional medicines could move from the bench to the bedside to improve patient prognosis with the ongoing advancement of clinical research and the sustained development of nanomedicine.…”

Protective effects of curcumin against osteoporosis and its molecular mechanisms: a recent review in preclinical trials

“…CUR, derived from natural plants, is one of the most common bioactive supplements used to treat various chronic diseases, such as cardiovascular diseases, diabetes, tumors, and osteoarthritis ( Hong et al, 2019 ; Abu-Taweel et al, 2020 ; Pourbagher-Shahri et al, 2021 ; Yang et al, 2022 ). In vivo and in vitro studies have shown that the beneficial effects of CUR on bone are primarily related to improved bone density and mechanical properties, indicating the possible use of CUR to prevent and treat bone diseases ( Barik et al, 2020 ). However, studies on CUR in patients with OP are relatively limited, but all of them reported excellent protective effect.…”