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Calcium phosphate (CaP) is the principal inorganic constituent of bone and teeth in vertebrates and has various applications in biomedical areas. Among various types of CaPs, amorphous calcium phosphate (ACP) is considered to have superior bioactivity and biodegradability. With regard to the instability of ACP, the phosphorus-containing molecules are usually adopted to solve this issue, but the specific roles of the molecules in the formation of nano-sized CaP have not been clearly clarified yet. Herein, alendronate, cyclophosphamide, zoledronate, and foscarnet are selected as the model molecules, and theoretical calculations were performed to elucidate the interaction between calcium ions and different model molecules. Subsequently, CaPs were prepared with the addition of the phosphorus-containing molecules. It is found that cyclophosphamide has limited influence on the generation of CaPs due to their weak interaction. During the co-precipitation process of Ca2+ and PO43-, the competitive relation among alendronate, zoledronate, and foscarnet plays critical roles in the produced inorganic-organic complex. Moreover, the biocompatibility of CaPs was also systematically evaluated. The DFT calculation provides a convincing strategy for predicting the structure of CaPs with various additives. This work is promising for designing CaP-based multifunctional drug delivery systems and tissue engineering materials.

Since their discovery, Black Phosphorus (BP)-based nanomaterials have received extensive attentions in the fields of electromechanics, optics and biomedicine, due to their remarkable properties and excellent biocompatibility. The most essential feature of BP is that it is composed of a single phosphorus element, which has a high degree of homology with the inorganic components of natural bone, therefore it has a full advantage in the treatment of bone defects. This review will first introduce the source, physicochemical properties, and degradation products of BP, then introduce the remodeling process of bone, and comprehensively summarize the progress of BP-based materials for bone therapy in the form of hydrogels, polymer membranes, microspheres, and three-dimensional (3D) printed scaffolds. Finally, we discuss the challenges and prospects of BP-based implant materials in bone immune regulation and outlook the future clinical application.

With the rapid development of population ageing, bone-related diseases seriously affecting the life of the elderly. Over the past few years, organoids, cell clusters with specific functions and structures that are self-induced from stem cells after three-dimensional culture in vitro, have been widely used for bone therapy. Moreover, organoid extracellular vesicles (OEVs) have emerging as promising cell-free nanocarriers due to their vigoroso physiological effects, significant biological functions, stable loading capacity, and great biocompatibility. In this review, we first provide a comprehensive overview of biogenesis, internalisation, isolation, and characterisation of OEVs. We then comprehensively highlight the differences between OEVs and traditional EVs. Subsequently, we present the applications of natural OEVs in disease treatment. We also summarise the engineering modifications of OEVs, including engineering parental cells and engineering OEVs after isolation. Moreover, we provide an outlook on the potential of natural and engineered OEVs in bone-related diseases. Finally, we critically discuss the advantages and challenges of OEVs in the treatment of bone diseases. We believe that a comprehensive discussion of OEVs will provide more innovative and efficient solutions for complex bone diseases.

Background: Correction of calcium, phosphorus, and parathyroid hormone disorders is the standard of treatment in nondialysis patients with chronic kidney disease-mineral and bone disorder (CKD-MBD). However, the side effects and adverse reactions are still the main problems. Moreover, the lack of protection of kidney function in the treatment dramatically affects patients' health. Although Traditional Chinese Medicine, specifically tonifying kidney and strengthen bone (TKSB) therapy, is wildly applied to patients with CKD-MBD in China, the evidence of TKSB therapy in the treatment of CKD-MBD is limited. Thus, we conducted this meta-analysis to evaluate the efficacy and safety of TKSB therapy combined with Western medicine (WM) for nondialysis patients with CKD-MBD., Methods: Two investigators conducted systematic research of randomized controlled trials of TKSB therapy for CKD-MBD from 7 electronic databases. Methodological quality evaluations were performed using the Cochrane collaboration tool, and data analysis was conducted by RevMan v5.3 software and STATA v15.0., Results: In total, 8 randomized controlled trials involving 310 patients met the criteria of meta-analysis. The complete results showed that compared with WM alone, TKSB treatment could improve the clinical efficacy rate (risk ratio = 4.49, 95% confidence interval [CI]: [2.64, 7.61], P  .00001), calcium (weighted mean difference [WMD] = 0.11, 95% CI: [0.08, 0.14], P < .00001), serum creatinine (WMD = 45.58, 95% CI: [32.35, 58.8], P < .00001) phosphorus (WMD = 0.11, 95% CI: [0.08, 0.13], P < .00001), parathyroid hormone (WMD = 16.72, 95% CI: [12.89, 20.55], P < .00001), blood urea nitrogen levels (WMD = 0.95, 95% CI: [0.26, 1.64], P = .007) on nondialysis patients with CKD-MBD, which was beneficial to improve the patients' bone metabolic state and renal function. In addition, evidence shows that, compared with WM alone, TKSB treatment is safe and does not increase side effects., Conclusion: The systematic review found that TKSB therapy combined with WM has a positive effect on improving renal function and correcting bone metabolism disorder in nondialysis patients with CKD-MBD, which shows that Traditional Chinese Medicine is effective and safe in treating CKD-MBD. However, more high-quality, large-sample, multicenter clinical trials should be conducted to assess the safety and efficacy of TKSB therapy in treating nondialysis patients with CKD-MBD.Systematic review registration: INPLASY2020120086., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2023 the Author(s). Published by Wolters Kluwer Health, Inc.)

The tumor microenvironment plays a central role in the onset and progression of cancer in the bone. Cancer cells, either from tumors originating in the bone or from metastatic cancer cells from other body systems, are located in specialized niches where they interact with different cells of the bone marrow. These interactions transform the bone into an ideal niche for cancer cell migration, proliferation, and survival and cause an imbalance in bone homeostasis that severely affects the integrity of the skeleton. During the last decade, preclinical studies have identified new cellular mechanisms responsible for the dependency between cancer cells and bone cells. In this review, we focus on osteocytes, long-lived cells residing in the mineral matrix that have recently been identified as key players in the spread of cancer in bone. We highlight the most recent discoveries on how osteocytes support tumor growth and promote bone disease. Additionally, we discuss how the reciprocal crosstalk between osteocytes and cancer cells provides the opportunity to develop new therapeutic strategies to treat cancer in the bone.

The aim of the current study is to prevent and reduce the number of bacterial infections in surgical implantation procedures. The hydroxyapatite is a calcium phosphate ceramic with important applications in the medicine and chemistry fields. The hydroxyapatite is a main mineral constituent of the hard tissues such as bones and teeth. The hydroxyapatite has remarkable properties including biocompatibility, bioactivity and ability to form a direct chemical bond with human hard tissues. Over the last decades, the biomedical orthopaedic and dentistry sectors have witnessed an unprecedented demand for a large variety and number of scaffolds, grafts, implants, and endo-prostheses. The increase in life expectancy, and the higher frequency of injuries and diseases are regarded as the main factors for this growing demand in orthopaedic and dental devices. The quality of life for millions of people has been drastically improved by using hydroxyapatite for bone repair and tissue regeneration. Recent findings in the realm of ion-substituted hydroxyapatite (HA) could pave the road towards significant developments in biomedicine, with an emphasis on a new generation of orthopaedic and dentistry applications, since such bioceramics are able to mimic the structural, compositional and mechanical properties of the bone mineral phase.

Calcium phosphate (CaP) is the principal inorganic constituent of bone and teeth in vertebrates and has various applications in biomedical areas. Among various types of CaPs, amorphous calcium phosphate (ACP) is considered to have superior bioactivity and biodegradability. With regard to the instability of ACP, the phosphorus-containing molecules are usually adopted to solve this issue, but the specific roles of the molecules in the formation of nano-sized CaP have not been clearly clarified yet. Herein, alendronate, cyclophosphamide, zoledronate, and foscarnet are selected as the model molecules, and theoretical calculations were performed to elucidate the interaction between calcium ions and different model molecules. Subsequently, CaPs were prepared with the addition of the phosphorus-containing molecules. It is found that cyclophosphamide has limited influence on the generation of CaPs due to their weak interaction. During the co-precipitation process of Ca 2+ and PO 4 3- , the competitive relation among alendronate, zoledronate, and foscarnet plays critical roles in the produced inorganic-organic complex. Moreover, the biocompatibility of CaPs was also systematically evaluated. The DFT calculation provides a convincing strategy for predicting the structure of CaPs with various additives. This work is promising for designing CaP-based multifunctional drug delivery systems and tissue engineering materials., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Jiang, Tao, Chen, Xue, Ding, Wang, Liu, Li and Su.)

Aim: To investigate asingle-walled carbon nanotube (SWCNT) joint to bisphosphonate agents of 5AEL, 5AFX, 4QPF, 3DYG, 2F92, 2I19 chelated to metal cations of Mg2+, Ca2+, Sr2+ due to the direct electron transfer principle which has been studied by density functional theory methods. Method: It has been accomplished the B3LYP/6-311+G(d,p)/LANL2DZ to estimate the susceptibility of SWCNT for adsorbing 5AEL, 5AFX, 4QPF, 3DYG, 2F92, 2I19 chelated to metal cations of Mg2+, Ca2+, Sr2+ through nuclear magnetic resonance and thermodynamic parameters. Results: The data explained that the feasibility of using SWCNT and bisphosphonate agents becomes the norm in metal chelating of delivery system, which has been selected through several bisphosphonate agents of 5AEL, 5AFX, 4QPF, 3DYG, 2F92, and 2I19 using DFT method due to physico-chemical properties of NMR and IR methodologies. [ABSTRACT FROM AUTHOR]

Regenerative biomaterials play a crucial role in the success of maxillofacial reconstructive procedures. Yet today, limited options are available when choosing polymeric biomaterials to treat critical size bony defects. Further, there is a requirement for 3D printable regenerative biomaterials to fabricate customized structures confined to the defect site. We present here a 3D printable composite formulation consisting of polycaprolactone (PCL) and silk fibroin microfibers and have established a robust protocol for fabricating customized 3D structures of complex geometry with the composite. The 3D printed composite scaffolds demonstrated higher compressive modulus than 3D printed scaffolds of PCL alone. Furthermore, the compressive modulus of PCL- Antheraea mylitta (AM) silk scaffolds is higher than that of the PCL- Bombyx mori (BM) silk scaffolds at their respective ratios. Compressive modulus of PCL-25AM silk scaffolds (73.4 MPa) is higher than that of PCL-25BM silk scaffolds (65.1 MPa). Compressive modulus of PCL-40AM silk scaffolds (106.1 MPa) is higher than that of PCL-40BM silk scaffolds (77.7 MPa). Moreover, we have isolated, characterized, and integrated human gingival mesenchymal stem cells (hGMSCs), an effective autologous cell source, onto the 3D printed scaffolds to evaluate their bone regeneration potential. The results demonstrated that PCL-silk microfiber composite scaffolds of Antheraea mylitta origin showed much higher bioactivity than the Bombyx mori ones because of arginine-glycine-aspartic acid (RGD) sequences present in the Antheraea mylitta silk fibroin protein favoring cell attachment and proliferation. By day 14, the metabolic activity of hGMSCs was highest in PCL-40AM (4.5 times higher than that at day 1). In addition, to show the translational potential of this work, we have fabricated a patient defect-specific model (mandible) using the CT scan obtained by the micro-CT imaging to understand the printability of the composite for fabricating complex structures to restore maxillofacial bony defects with precision when applied in a clinical scenario.

With the development of society, traumatic bone defects caused by accidents, diseases and surgeries have become common, eventually resulting in an increase in bone defects. The treatment of bone defects is characterized by a long period of treatment, high cost and uncontrollable outcomes. Also, it results in complications such as infection and bone discontinuity. Hence, due to this situation, the physical, mental and financial aspects of the patient are severely affected. What's more, such outcomes pose a challenge to orthopaedic surgeons. As a result, bone therapy and bone repair have become a hot topic of interest. In repairing bone defects, materials other than autogenous bone are still unable to provide good biocompatibility, osteogenesis, osteoconductivity and osteoinduction properties at the same time. In addition, the scarcity of autologous bone sources has forced the search for new autologous bone replacement materials. Metal organic frameworks (MOFs) are a new class of developed functional materials that have been widely used in the biomedical field during the recent years due to their porous nature, large specific surface area and diverse structures. With the progress in the investigation into bone treatment and repair, more and more investigators are using MOFs in bone therapy and bone repair. With these viewpoints, in the present perspective, the use of MOFs in bone therapy and bone repair has been summarized, and an insight into the future of MOFs in bone therapy and bone repair has been provided.

Due to their prominent physicochemical properties, 2D materials are broadly applied in biomedicine. Currently, 2D materials have achieved great success in treating many diseases such as cancer and tissue engineering as well as bone therapy. Based on their different characteristics, 2D materials could function in various ways in different bone diseases. Herein, the application of 2D materials in bone tissue engineering, joint lubrication, infection of orthopedic implants, bone tumors, and osteoarthritis are firstly reviewed comprehensively together. Meanwhile, different mechanisms by which 2D materials function in each disease reviewed below are also reviewed in detail, which in turn reveals the versatile functions and application of 2D materials. At last, the outlook on how to further broaden applications of 2D materials in bone therapies based on their excellent properties is also discussed., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Correction of calcium (Ca), phosphorus (P), and parathyroid hormone (PTH) disorders is the standard of treatment in non-dialysis patients with chronic kidney disease-mineral and bone disorder (CKD-MBD), but the side effects and adverse reactions brought by western medicine (WM) are still the main problems. More importantly, the lack of protection of kidney function in the treatment greatly affects the health of patients. Although traditional Chinese medicine (TCM), specifically tonifying kidney and strengthen bone (TKSB) therapy is wildly applied for patients with CKD-MBD in China, the evidence of TKSB therapy in the treatment of CKD-MBD is limited. Thus, we pretent to conduct this protocol to evaluate the efficacy and safety of TKSB therapy combined with WM for non-dialysis patients with CKD-MBD., Methods: A system research of randomized controlled trials (RCTs) of TKSB therapy for CKD-MBD will be conducted by 2 investigators from 7 electronic databases. Methodological quality evaluations will be performed by using the Cochrane collaboration tool and data analysis will be conducted by RevMan V5.3 software and STATA v15.0., Results: The results of this paper will be submitted to a peer-reviewed journal for publication., Conclusion: This research will determine the safety and efficacy of TKSB therapy in treating non-dialysis patients with CKD-MBD., Inplasy Registration Number: INPLASY2020120086., Competing Interests: The authors have no conflicts of interest to disclose., (Copyright © 2021 the Author(s). Published by Wolters Kluwer Health, Inc.)

This study evaluated the application of laser-induced bone therapy (LIBT) to reduce implant healing time in rat tibia. Twenty 10-week-old female Sprague-Dawlay rats were used. The rats received laser irradiation (laser group) or sham operation (control group) on either side of the tibia. Five days after invasion, titanium implants were inserted in proximal tibia. Five, 10, and 20 days after implant placement, tibiae were collected. After taking micro-CT and performing a torque test, the tibiae were decalcified and 8-μm-thick sections were prepared. Specimens were stained with hematoxylin and eosin. Results. Micro-CT images, removal torque values, and histomorphometric analysis data demonstrated a significantly accelerated bone formation in the laser group earlier in the healing process. Conclusion. The use of laser irradiation was effective in promoting bone formation and acquiring osseointegration of titanium implants inserted in rat tibia. LIBT may be suitable for use in implant therapy.