Amorphous Calcium Magnesium Phosphate Nanocomposites with Superior Osteogenic Activity for Bone Regeneration

Abstract The seek of bioactive materials for promoting bone regeneration is a challenging and long-term task. Functionalization with inorganic metal ions or drug molecules are considered effective strategies to improve the bioactivity of various existing biomaterials. Herein, amorphous calcium magnesium phosphate (ACMP) nanoparticles and simvastatin (SIM)-loaded ACMP (ACMP/SIM) nanocomposites were developed via a simple coprecipitation strategy. The physiochemical property of ACMP/SIM were explored using transmission electron microscope (TEM), Fourier transform infrared spectroscopy (FTIR), powder X-ray diffraction (XRD) and high performance liquid chromatograph (HPLC), and the role of Mg2+ in the formation of ACMP/SIM was revealed using X-ray absorption near-edge structure (XANES). After that, the transformation process of ACMP/SIM in simulated body fluid (SBF) was also tracked to simulate and explore the in vivo mineralization performance of materials. We find that ACMP/SIM releases ions of Ca2+, Mg2+ and PO43-, when it is immersed in SBF at 37 °C, and a phase transformation occured during which the initially amorphous ACMP turns into self-assembled hydroxyapatite (HAP). Furthermore, ACMP/SIM displays high cytocompatibility and promotes the proliferation and osteogenic differentiation of MC3T3-E1 cells. For the in vivo studies, lamellar ACMP/SIM/Collagen scaffolds with aligned pore structures were prepared and used to repair a rat defect model in calvaria. ACMP/SIM/Collagen scaffolds show a positive effect in promoting the regeneration of calvaria defect after 12 weeks. The bioactive ACMP/SIM nanocomposites are promising as bone repair materials. Considering the facile preparation process and superior in vitro/vivo bioactivity, the as-prepared ACMP/SIM would be a potential candidate for bone related biomedical applications.

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In Vivo Analysis of the Biocompatibility and Immune Response of Jellyfish Collagen Scaffolds and its Suitability for Bone Regeneration

International Journal of Molecular Sciences ◽

10.3390/ijms21124518 ◽

2020 ◽

Vol 21 (12) ◽

pp. 4518 ◽

Cited By ~ 2

Author(s):

Iris Flaig ◽

Milena Radenković ◽

Stevo Najman ◽

Annica Pröhl ◽

Ole Jung ◽

...

Keyword(s):

Immune Response ◽

Connective Tissue ◽

Bone Regeneration ◽

Tissue Regeneration ◽

In Vivo Studies ◽

M2 Macrophages ◽

Collagen Scaffolds ◽

Porcine Pericardium ◽

M1 And M2 Macrophages

Jellyfish collagen, which can be defined as “collagen type 0” due to its homogeneity to the mammalian types I, II, III, V, and IX and its batch-to-batch consistent producibility, is of special interest for different medical applications related to (bone) tissue regeneration as an alternative to mammalian collagen-based biomaterials. However, no in vivo studies regarding the induction of M1- and M2-macrophages and their time-dependent ration as well as the analysis of the bone regeneration capacity of jellyfish collagen scaffolds have been conducted until now. Thus, the goal of this study was to determine the nature of the immune response to jellyfish collagen scaffolds and their bone healing capacities. Two in vivo studies using established implantation models, i.e., the subcutaneous and the calvarian implantation model in Wistar rats, were conducted. Furthermore, specialized histological, histopathological, and histomorphometrical methods have been used. As a control biomaterial, a collagen scaffold, originating from porcine pericardium, which has already been stated as biocompatible, was used for the subcutaneous study. The results of the present study show that jellyfish collagen scaffolds are nearly completely resorbed until day 60 post implantation by stepwise integration within the subcutaneous connective tissue mediated mainly by macrophages and single multinucleated giant cells. Interestingly, the degradation process ended in a vessel rich connective tissue that is understood to be an optimal basis for tissue regeneration. The study results showed an overall weaker immune response to jellyfish collagen than to porcine pericardium matrices by the induction of significantly lower numbers of macrophages together with a more balanced occurrence of M1- and M2-macrophages. However, both collagen-based biomaterials induced balanced numbers of both macrophage subtypes, which supports their good biocompatibility. Moreover, the histomorphometrical results for the calvarial implantation of the jellyfish scaffolds revealed an average of 46.20% de novo bone formation at day 60, which was significantly higher compared to the control group. Thereby, the jellyfish collagen scaffolds induced also significantly higher numbers of anti-inflammatory macrophages within the bony implantation beds. Altogether, the results show that the jellyfish collagen scaffolds allowed for a directed integration behavior, which is assumed to be in accordance with the concept of Guided Bone Regeneration (GBR). Furthermore, the jellyfish collagen scaffolds induced a long-term anti-inflammatory macrophage response and an optimal vascularization pattern within their implant beds, thus showing excellent biocompatibility and (bone) tissue healing properties.

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In Vivo Investigation of the Distribution and the Local Speciation of Selenium inAlliumcepa L. by Means of Microscopic X-ray Absorption Near-Edge Structure Spectroscopy and Confocal Microscopic X-ray Fluorescence Analysis

Analytical Chemistry ◽

10.1021/ac060380s ◽

2006 ◽

Vol 78 (22) ◽

pp. 7616-7624 ◽

Cited By ~ 49

Author(s):

Ewa Bulska ◽

Irena A. Wysocka ◽

Małgorzata H. Wierzbicka ◽

Kristof Proost ◽

Koen Janssens ◽

...

Keyword(s):

Fluorescence Analysis ◽

Edge Structure ◽

X Ray ◽

X Ray Absorption

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In-Vivo Degradation Behavior and Osseointegration of 3D Powder-Printed Calcium Magnesium Phosphate Cement Scaffolds

Materials ◽

10.3390/ma14040946 ◽

2021 ◽

Vol 14 (4) ◽

pp. 946

Author(s):

Katharina Kowalewicz ◽

Elke Vorndran ◽

Franziska Feichtner ◽

Anja-Christina Waselau ◽

Manuel Brueckner ◽

...

Keyword(s):

Three Dimensional ◽

Bone Substitutes ◽

Magnesium Phosphate ◽

Degradation Behavior ◽

Micro Computed Tomography ◽

Calcium Magnesium ◽

Interest In Research ◽

In Vivo Degradation ◽

Volume Decrease

Calcium magnesium phosphate cements (CMPCs) are promising bone substitutes and experience great interest in research. Therefore, in-vivo degradation behavior, osseointegration and biocompatibility of three-dimensional (3D) powder-printed CMPC scaffolds were investigated in the present study. The materials Mg225 (Ca0.75Mg2.25(PO4)2) and Mg225d (Mg225 treated with diammonium hydrogen phosphate (DAHP)) were implanted as cylindrical scaffolds (h = 5 mm, Ø = 3.8 mm) in both lateral femoral condyles in rabbits and compared with tricalcium phosphate (TCP). Treatment with DAHP results in the precipitation of struvite, thus reducing pore size and overall porosity and increasing pressure stability. Over 6 weeks, the scaffolds were evaluated clinically, radiologically, with Micro-Computed Tomography (µCT) and histological examinations. All scaffolds showed excellent biocompatibility. X-ray and in-vivo µCT examinations showed a volume decrease and increasing osseointegration over time. Structure loss and volume decrease were most evident in Mg225. Histologically, all scaffolds degraded centripetally and were completely traversed by new bone, in which the remaining scaffold material was embedded. While after 6 weeks, Mg225d and TCP were still visible as a network, only individual particles of Mg225 were present. Based on these results, Mg225 and Mg225d appear to be promising bone substitutes for various loading situations that should be investigated further.

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Bone defect reconstruction via endochondral ossification: A developmental engineering strategy

Journal of Tissue Engineering ◽

10.1177/20417314211004211 ◽

2021 ◽

Vol 12 ◽

pp. 204173142110042

Author(s):

Rao Fu ◽

Chuanqi Liu ◽

Yuxin Yan ◽

Qingfeng Li ◽

Ru-Lin Huang

Keyword(s):

Bone Regeneration ◽

Bone Defect ◽

Bone Repair ◽

Endochondral Ossification ◽

Current Knowledge ◽

Endochondral Bone ◽

Defect Reconstruction ◽

Hypoxic Conditions ◽

Bone Defect Reconstruction

Traditional bone tissue engineering (BTE) strategies induce direct bone-like matrix formation by mimicking the embryological process of intramembranous ossification. However, the clinical translation of these clinical strategies for bone repair is hampered by limited vascularization and poor bone regeneration after implantation in vivo. An alternative strategy for overcoming these drawbacks is engineering cartilaginous constructs by recapitulating the embryonic processes of endochondral ossification (ECO); these constructs have shown a unique ability to survive under hypoxic conditions as well as induce neovascularization and ossification. Such developmentally engineered constructs can act as transient biomimetic templates to facilitate bone regeneration in critical-sized defects. This review introduces the concept and mechanism of developmental BTE, explores the routes of endochondral bone graft engineering, highlights the current state of the art in large bone defect reconstruction via ECO-based strategies, and offers perspectives on the challenges and future directions of translating current knowledge from the bench to the bedside.

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Three-Dimensional Zirconia-Based Scaffolds for Load-Bearing Bone-Regeneration Applications: Prospects and Challenges

Materials ◽

10.3390/ma14123207 ◽

2021 ◽

Vol 14 (12) ◽

pp. 3207

Author(s):

Kumaresan Sakthiabirami ◽

Vaiyapuri Soundharrajan ◽

Jin-Ho Kang ◽

Yunzhi Peter Yang ◽

Sang-Won Park

Keyword(s):

Bone Regeneration ◽

Biological Activities ◽

Three Dimensional ◽

In Vivo Studies ◽

High Mechanical Strength ◽

Real World Applications ◽

3D Fabrication ◽

Dental Applications

The design of zirconia-based scaffolds using conventional techniques for bone-regeneration applications has been studied extensively. Similar to dental applications, the use of three-dimensional (3D) zirconia-based ceramics for bone tissue engineering (BTE) has recently attracted considerable attention because of their high mechanical strength and biocompatibility. However, techniques to fabricate zirconia-based scaffolds for bone regeneration are in a stage of infancy. Hence, the biological activities of zirconia-based ceramics for bone-regeneration applications have not been fully investigated, in contrast to the well-established calcium phosphate-based ceramics for bone-regeneration applications. This paper outlines recent research developments and challenges concerning numerous three-dimensional (3D) zirconia-based scaffolds and reviews the associated fundamental fabrication techniques, key 3D fabrication developments and practical encounters to identify the optimal 3D fabrication technique for obtaining 3D zirconia-based scaffolds suitable for real-world applications. This review mainly summarized the articles that focused on in vitro and in vivo studies along with the fundamental mechanical characterizations on the 3D zirconia-based scaffolds.

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Zn-Containing Membranes for Guided Bone Regeneration in Dentistry

Polymers ◽

10.3390/polym13111797 ◽

2021 ◽

Vol 13 (11) ◽

pp. 1797

Author(s):

Manuel Toledano ◽

Marta Vallecillo-Rivas ◽

María T. Osorio ◽

Esther Muñoz-Soto ◽

Manuel Toledano-Osorio ◽

...

Keyword(s):

Mechanical Properties ◽

Bone Regeneration ◽

Bone Healing ◽

Bone Repair ◽

Complex Modulus ◽

Bacterial Colonization ◽

Guided Bone Regeneration ◽

M2 Macrophage

Barrier membranes are employed in guided bone regeneration (GBR) to facilitate bone in-growth. A bioactive and biomimetic Zn-doped membrane with the ability to participate in bone healing and regeneration is necessary. The aim of the present study is to state the effect of doping the membranes for GBR with zinc compounds in the improvement of bone regeneration. A literature search was conducted using electronic databases, such as PubMed, MEDLINE, DIMDI, Embase, Scopus and Web of Science. A narrative exploratory review was undertaken, focusing on the antibacterial effects, physicochemical and biological properties of Zn-loaded membranes. Bioactivity, bone formation and cytotoxicity were analyzed. Microstructure and mechanical properties of these membranes were also determined. Zn-doped membranes have inhibited in vivo and in vitro bacterial colonization. Zn-alloy and Zn-doped membranes attained good biocompatibility and were found to be non-toxic to cells. The Zn-doped matrices showed feasible mechanical properties, such as flexibility, strength, complex modulus and tan delta. Zn incorporation in polymeric membranes provided the highest regenerative efficiency for bone healing in experimental animals, potentiating osteogenesis, angiogenesis, biological activity and a balanced remodeling. Zn-loaded membranes doped with SiO2 nanoparticles have performed as bioactive modulators provoking an M2 macrophage increase and are a potential biomaterial for promoting bone repair. Zn-doped membranes have promoted pro-healing phenotypes.

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Early commissioning results for spectroscopic X-ray Nano-Imaging Beamline BL 7C sXNI at PLS-II

Journal of Synchrotron Radiation ◽

10.1107/s1600577517013972 ◽

2017 ◽

Vol 24 (6) ◽

pp. 1276-1282 ◽

Cited By ~ 8

Author(s):

Sangsul Lee ◽

Ik hwan Kwon ◽

Jae-Young Kim ◽

Sung-Sun Yang ◽

Sechang Kang ◽

...

Keyword(s):

Lithium Iron Phosphate ◽

Phase Distribution ◽

Lithium Ion ◽

Feedback System ◽

Double Crystal ◽

Pilot Studies ◽

Beam Position ◽

Edge Structure ◽

X Ray

For spectral imaging of chemical distributions using X-ray absorption near-edge structure (XANES) spectra, a modified double-crystal monochromator, a focusing plane mirrors system and a newly developed fluorescence-type X-ray beam-position monitoring and feedback system have been implemented. This major hardware upgrade provides a sufficiently stable X-ray source during energy scanning of more than hundreds of eV for acquisition of reliable XANES spectra in two-dimensional and three-dimensional images. In recent pilot studies discussed in this paper, heavy-metal uptake by plant rootsin vivoand iron's phase distribution in the lithium–iron–phosphate cathode of a lithium-ion battery have been imaged. Also, the spatial resolution of computed tomography has been improved from 70 nm to 55 nm by means of run-out correction and application of a reconstruction algorithm.

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Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair

Bone and Joint Research ◽

10.1302/2046-3758.710.bjr-2018-0015.r2 ◽

2018 ◽

Vol 7 (10) ◽

pp. 548-560 ◽

Cited By ~ 8

Author(s):

I. Qayoom ◽

D. B. Raina ◽

A. Širka ◽

Š. Tarasevičius ◽

M. Tägil ◽

...

Keyword(s):

Bone Resorption ◽

Bone Regeneration ◽

Bone Morphogenetic Proteins ◽

Bone Repair ◽

Biological Effects ◽

Research Groups ◽

Preclinical Models ◽

Implant Fixation ◽

Local Use

During the last decades, several research groups have used bisphosphonates for local application to counteract secondary bone resorption after bone grafting, to improve implant fixation or to control bone resorption caused by bone morphogenetic proteins (BMPs). We focused on zoledronate (a bisphosphonate) due to its greater antiresorptive potential over other bisphosphonates. Recently, it has become obvious that the carrier is of importance to modulate the concentration and elution profile of the zoledronic acid locally. Incorporating one fifth of the recommended systemic dose of zoledronate with different apatite matrices and types of bone defects has been shown to enhance bone regeneration significantly in vivo. We expect the local delivery of zoledronate to overcome the limitations and side effects associated with systemic usage; however, we need to know more about the bioavailability and the biological effects. The local use of BMP-2 and zoledronate as a combination has a proven additional effect on bone regeneration. This review focuses primarily on the local use of zoledronate alone, or in combination with bone anabolic factors, in various preclinical models mimicking different orthopaedic conditions. Cite this article: I. Qayoom, D. B. Raina, A. Širka, Š. Tarasevičius, M. Tägil, A. Kumar, L. Lidgren. Anabolic and antiresorptive actions of locally delivered bisphosphonates for bone repair: A review. Bone Joint Res 2018;7:548–560. DOI: 10.1302/2046-3758.710.BJR-2018-0015.R2.

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