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Although bone tissues possess an intrinsic capacity for repair, there are cases where bone healing is either impaired or insufficient, such as fracture non-union, osteoporosis, osteomyelitis, and cancers. In these cases, treatments like surgical interventions are used, either alone or in combination with bioactive agents, to promote tissue repair and manage associated clinical complications. Improving the efficacy of bioactive agents often requires carriers, with biomaterials being a pivotal player. In this review, we discuss the role of biomaterials in realizing the local and systemic delivery of biomolecules to the bone tissue. The versatility of biomaterials enables design of carriers with the desired loading efficiency, release profile, and on-demand delivery. Besides local administration, systemic administration of drugs is necessary to combat diseases like osteoporosis, warranting bone-targeting drug delivery systems. Thus, chemical moieties with the affinity towards bone extracellular matrix components like apatite minerals have been widely utilized to create bone-targeting carriers with better biodistribution, which cannot be achieved by the drugs alone. Bone-targeting carriers combined with the desired drugs or bioactive agents have been extensively investigated to enhance bone healing while minimizing off-target effects. Herein, these advancements in the field have been systematically reviewed. Drug delivery is imperative when surgical interventions are not sufficient to address various bone diseases/defects. Biomaterial-assisted delivery systems have been designed to provide drugs with the desired loading efficiency, sustained release, and on-demand delivery to enhance bone healing. By surveying recent advances in the field, this review outlines the design of biomaterials as carriers for the local and systemic delivery of bioactive agents to the bone tissue. Particularly, biomaterials that bear chemical moieties with affinity to bone are attractive, as they can present the desired bioactive agents to the bone tissue efficiently and thus enhance the drug efficacy for bone repair. [ABSTRACT FROM AUTHOR]

Extracellular adenosine has been shown to play a key role in maintaining bone health and could potentially be used to treat bone loss. However, systemic administration of exogenous adenosine to treat bone disorders remains a challenge due to the ubiquitous presence of adenosine receptors in different organs and the short half-life of adenosine in circulation. Towards this, we have developed a bone-targeting nanocarrier and determined its potential for systemic administration of adenosine. The nanocarrier, synthesized via emulsion suspension photopolymerization, is comprised of hyaluronic acid (HA) copolymerized with phenylboronic acid (PBA), a moiety that can form reversible bonds with adenosine. The bone binding affinity of the nanocarrier was achieved by alendronate (Aln) conjugation. Nanocarriers functionalized with the alendronate (Aln-NC) showed a 45% higher accumulation in the mice vertebrae in vivo compared to those lacking alendronate molecules (NCs). Systemic administration of adenosine via bone-targeting nanocarriers (Aln-NC) attenuated bone loss in ovariectomized (OVX) mice. Furthermore, bone tissue of mice treated with adenosine-loaded Aln-NC displayed trabecular bone characteristics comparable to healthy controls as shown by microcomputed tomography, histochemical staining, bone labeling, and mechanical strength. Overall, our results demonstrate the use of a bone-targeting nanocarrier towards systemic administration of adenosine and its application in treating bone degenerative diseases such as osteoporosis. [Display omitted] [ABSTRACT FROM AUTHOR]

• A comprehensive arsenic awareness index (CAAI) was developed. • 15 key awareness drivers (KADs) were derived using hybrid feature selection. • Bangladesh farmers were less aware of the food component of CAAI. • Stakeholder interventions and cropping practices influenced arsenic awareness. • CART and SCT models achieved an overall prediction accuracy of 84%. High levels of arsenic in drinking water and food materials continue to pose a global health challenge. Over 127 million people alone in Bangladesh (BD) and West Bengal (WB) state of India are exposed to elevated levels of arsenic in drinking water. Despite decades of research and outreach, arsenic awareness in communities continue to be low. Specifically, very few studies reported arsenic awareness among low-income farming communities. A comprehensive approach to assess arsenic awareness is a key step in identifying research and development priorities so that appropriate stakeholder engagement may be designed to tackle arsenic menace. In this study, we developed a comprehensive arsenic awareness index (CAAI) and identified key awareness drivers (KADs) of arsenic to help evaluate farmers' preferences in dealing with arsenic in the environment. The CAAI and KADs were developed using a questionnaire survey in conjunction with ten machine learning (ML) models coupled with a hybrid feature selection approach. Two questionnaire surveys comprising of 73 questions covering health, water and community, and food were conducted in arsenic-affected areas of WB and BD. Comparison of CAAIs showed that the BD farmers were generally more arsenic-aware (CAAI = 7.7) than WB farmers (CAAI = 6.8). Interestingly, the reverse was true for the awareness linked to arsenic in the food chain. Application of hybrid feature selection identified 15 KADs, which included factors related to stakeholder interventions and cropping practices instead of commonly perceived factors such as age, gender and income. Among ML algorithms, classification and regression trees and single C5.0 tree could estimate CAAIs with an average accuracy of 84%. Both communities agreed on policy changes on water testing and clean water supply. The CAAI and KADs combination revealed a contrasting arsenic awareness between the two farming communities, albeit their cultural similarities. Specifically, our study shows the need for increasing awareness of risks through the food chain in BD, whereas awareness campaigns should be strengthened to raise overall awareness in WB possibly through media channels as deemed effective in BD. [ABSTRACT FROM AUTHOR]