Mechanisms of in Vivo Degradation and Resorption of Calcium Phosphate Based Biomaterials.
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ABSTRACT:
SUBMITTER: Sheikh Z
PROVIDER: S-EPMC5458904 | biostudies-other | 2015 Nov
REPOSITORIES: biostudies-other
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Project description:Maxillary sinus augmentation is often necessary prior to implantology procedure, in particular in cases of atrophic posterior maxilla. In this context, bone substitute biomaterials made of biphasic calcium phosphates, produced by three-dimensional additive manufacturing were shown to be highly biocompatible with an efficient osteoconductivity, especially when combined with cell-based tissue engineering. Thus, in the present research, osteoinduction and osteoconduction properties of biphasic calcium-phosphate constructs made by direct rapid prototyping and engineered with ovine-derived amniotic epithelial cells or amniotic fluid cells were evaluated. More in details, this preclinical study was performed using adult sheep targeted to receive scaffold alone (CTR), oAFSMC, or oAEC engineered constructs. The grafted sinuses were explanted at 90 days and a cross-linked experimental approach based on Synchrotron Radiation microCT and histology analysis was performed on the complete set of samples. The study, performed taking into account the distance from native surrounding bone, demonstrated that no significant differences occurred in bone regeneration between oAEC-, oAFMSC-cultured, and Ctr samples and that there was a predominant action of the osteoconduction versus the stem cells osteo-induction. Indeed, it was proven that the newly formed bone amount and distribution decreased from the side of contact scaffold/native bone toward the bulk of the scaffold itself, with almost constant values of morphometric descriptors in volumes more than 1 mm from the border.
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Project description:Calcium phosphate cements (CPCs) represent excellent bone substitute materials due to their biocompatibility and injectability. However, their poor degradability and lack of macroporosity limits bone regeneration. The addition of poly(d,l-lactic-co-glycolic acid) (PLGA) particles improves macroporosity and therefore late stage material degradation. CPC degradation and hence, bone formation at an early stage remains challenging, due to the delayed onset of PLGA degradation (i.e., after 2-3 weeks). Consequently, we here explored multimodal porogen platforms based on sucrose porogens (for early pore formation) and PLGA porogens (for late pore formation) to enhance CPC degradation and analyzed mechanical properties, dynamic in vitro degradation and in vivo performance in a rat femoral bone defect model. Porogen addition to CPC showed to decrease compressive strength of all CPC formulations; transition of the crystal phase upon in vitro incubation increased compressive strength. Although dynamic in vitro degradation showed rapid sucrose dissolution within 1 week, no additional effects on CPC degradation or bone formation were observed upon in vivo implantation. © 2019 The Authors. journal Of Biomedical Materials Research Part A Published By Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 1713-1722, 2019.
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Project description:Compared to other materials such as 45S5 bioactive glass (BG), ?-tricalcium phosphate (?-TCP)-based bone substitutes such as Vitoss show limited material-driven stimulation of osteogenesis and/or angiogenesis. The unfavorable degradation kinetics of ?-TCP-based bone substitutes may result in an imbalance between resorption and osseous regeneration. Composite materials like Vitoss BA (Vitoss supplemented with 20 wt % 45S5-BG particles) might help to overcome these limitations. However, the influence of BG particles in Vitoss BA compared to unsupplemented Vitoss on osteogenesis, resorption behavior, and angiogenesis is not yet described. In this study, Vitoss and Vitoss BA scaffolds were seeded with human mesenchymal stromal cells before subcutaneous implantation in immunodeficient mice for 10 weeks. Scaffold resorption was monitored by micro-computed tomography, while osteoid formation and vascularization were assessed by histomorphometry and gene expression analysis. Whilst slightly more osteoid and improved angiogenesis were found in Vitoss BA, maturation of the osteoid was more advanced in Vitoss scaffolds. The volume of Vitoss implants decreased significantly, combined with a significantly increased presence of resorbing cells, whilst the volume remained stable in Vitoss BA scaffolds. Future studies should evaluate the interaction of 45S5-BG with resorbing cells and bone precursor cells in greater detail to improve the understanding and application of ?-TCP/45S5-BG composite bone substitute materials.
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Project description:In the past few years, we have demonstrated the efficacy of a nanoparticle system, super carbonate apatite (sCA), for the in vivo delivery of siRNA/miRNA. Intravenous injection of sCA loaded with small RNAs results in safe, high tumor delivery in mouse models. To further improve the efficiency of tumor delivery and avoid liver toxicity, we successfully developed an inorganic nanoparticle device (iNaD) via high-frequency ultrasonic pulverization combined with PEG blending during the production of sCA. Compared to sCA loaded with 24 μg of miRNA, systemic administration of iNaD loaded with 0.75 μg of miRNA demonstrated similar delivery efficiency to mouse tumors with little accumulation in the liver. In the mouse therapeutic model, iNaD loaded with 3 μg of the tumor suppressor small RNA MIRTX resulted in an improved anti-tumor effect compared to sCA loaded with 24 μg. Our findings on the bio-distribution and therapeutic effect of iNaD provide new perspectives for future nanomedicine engineering.
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Project description:The state-of-the-art of biocomposites and hybrid biomaterials based on calcium orthophosphates that are suitable for biomedical applications is presented in this review. Since these types of biomaterials offer many significant and exciting possibilities for hard tissue regeneration, this subject belongs to a rapidly expanding area of biomedical research. Through successful combinations of the desired properties of matrix materials with those of fillers (in such systems, calcium orthophosphates might play either role), innovative bone graft biomaterials can be designed. Various types of biocomposites and hybrid biomaterials based on calcium orthophosphates, either those already in use or being investigated for biomedical applications, are extensively discussed. Many different formulations, in terms of the material constituents, fabrication technologies, structural and bioactive properties as well as both in vitro and in vivo characteristics, have already been proposed. Among the others, the nanostructurally controlled biocomposites, those containing nanodimensional compounds, biomimetically fabricated formulations with collagen, chitin and/or gelatin as well as various functionally graded structures seem to be the most promising candidates for clinical applications. The specific advantages of using biocomposites and hybrid biomaterials based on calcium orthophosphates in the selected applications are highlighted. As the way from the laboratory to the hospital is a long one, and the prospective biomedical candidates have to meet many different necessities, this review also examines the critical issues and scientific challenges that require further research and development.
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Project description:Tissue engineering is promising to meet the increasing need for bone regeneration. Nanostructured calcium phosphate (CaP) biomaterials/scaffolds are of special interest as they share chemical/crystallographic similarities to inorganic components of bone. Three applications of nano-CaP are discussed in this review: nanostructured calcium phosphate cement (CPC); nano-CaP composites; and nano-CaP coatings. The interactions between stem cells and nano-CaP are highlighted, including cell attachment, orientation/morphology, differentiation and in vivo bone regeneration. Several trends can be seen: (i) nano-CaP biomaterials support stem cell attachment/proliferation and induce osteogenic differentiation, in some cases even without osteogenic supplements; (ii) the influence of nano-CaP surface patterns on cell alignment is not prominent due to non-uniform distribution of nano-crystals; (iii) nano-CaP can achieve better bone regeneration than conventional CaP biomaterials; (iv) combining stem cells with nano-CaP accelerates bone regeneration, the effect of which can be further enhanced by growth factors; and (v) cell microencapsulation in nano-CaP scaffolds is promising for bone tissue engineering. These understandings would help researchers to further uncover the underlying mechanisms and interactions in nano-CaP stem cell constructs in vitro and in vivo, tailor nano-CaP composite construct design and stem cell type selection to enhance cell function and bone regeneration, and translate laboratory findings to clinical treatments.
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Project description:This article describes the synthesis of anionic polymer brushes and their mineralization with calcium phosphate. The brushes are based on poly(3-sulfopropyl methacrylate potassium salt) providing a highly charged polymer brush surface. Homogeneous brushes with reproducible thicknesses are obtained via surface-initiated atom transfer radical polymerization. Mineralization with doubly concentrated simulated body fluid yields polymer/inorganic hybrid films containing AB-Type carbonated hydroxyapatite (CHAP), a material resembling the inorganic component of bone. Moreover, growth experiments using Dictyostelium discoideum amoebae demonstrate that the mineral-free and the mineral-containing polymer brushes have a good biocompatibility suggesting their use as biocompatible surfaces in implantology or related fields.
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Project description:Objective: The objective of this study is to compare the bone induction of five kinds of calcium phosphate (Ca-P) biomaterials implanted in mice and explore the vascularization and particle-size-related osteoinductive mechanism. Methods: The following five kinds of Ca-P biomaterials including hydroxyapatite (HA) and/or tricalcium phosphate (TCP) were implanted in the muscle of 30 BALB/c mice (n = 6): 20 nm HA (20HA), 60 nm HA (60HA), 12 µm HA (12HA), 100 nm TCP (100TCP) and 12 µm HA + 100 nm TCP (HATCP). Then, all animals were put on a treadmill to run 30 min at a 6 m/h speed each day. Five and ten weeks later, three mice of each group were killed, and the samples were harvested to assess the osteoinductive effects by hematoxylin eosin (HE), Masson's trichrome and safranine-fast green stainings, and the immunohistochemistry of the angiogenesis and osteogenesis markers CD31 and type I collagen (ColI). Results: The numbers of blood vessels were 139 ±&nbsp;29,&nbsp;118&nbsp;±&nbsp;25,&nbsp;78&nbsp;±&nbsp;15,&nbsp;65&nbsp;±&nbsp;14 in groups HATCP, 100TCP, 60HA and 20HA, respectively, which were significantly higher than that of group 12HA (12 ± 5) in week 5 (p < 0.05). The area percentages of new bone tissue were (7.33 ± 1.26)% and (8.49 ±&nbsp;1.38)% in groups 100TCP and HATCP, respectively, which were significantly higher than those in groups 20HA (3.27 ±&nbsp;0.38)% and 60HA (3.43 ±&nbsp;0.27)% (p < 0.05); however, no bone tissue was found in group 12HA 10 weeks after transplantation. The expression of CD31 was positive in new blood vessels, and the expression of ColI was positive in new bone tissue. Conclusions: Nanoscale Ca-P biomaterials could induce osteogenesis in mice muscle, and the osteoinductive effects of TCP were about 124% higher than those of 20HA and 114% higher than those of 60HA. The particle size of the biomaterials affected angiogenesis and osteogenesis. There was a positive correlation between the number of blood vessels and the area percentage of new bone tissue; therefore, osteoinduction is closely related to vascularization. Our results provide an experimental basis for the synthesis of calcium-phosphorus matrix composites and for further exploration of the osteoinductive mechanism.
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Project description:Here, we demonstrate the in vivo efficacy of glucose microparticles (GMPs) to serve as porogens within calcium phosphate cements (CPCs) to obtain a fast-degrading bone substitute material. Composites were fabricated incorporating 20 wt% GMPs at two different GMP size ranges (100-150 ?m (GMP-S) and 150-300 ?m (GMP-L)), while CPC containing 20 wt% poly(lactic-co-glycolic acid) microparticles (PLGA) and plain CPC served as controls. After 2 and 8 weeks implantation in a rat femoral condyle defect model, specimens were retrieved and analyzed for material degradation and bone formation. Histologically, no adverse tissue response to any of the CPC-formulations was observed. All CPC-porogen formulations showed faster degradation compared to plain CPC control, but only GMP-containing formulations showed higher amounts of new bone formation compared to plain CPC controls. After 8 weeks, only CPC-porogen formulations with GMP-S or PLGA porogens showed higher degradation compared to plain CPC controls. Overall, the inclusion of GMPs into CPCs resulted in a macroporous structure that initially accelerated the generation of new bone. These findings highlight the efficacy of a novel approach that leverages simple porogen properties to generate porous CPCs with distinct degradation and bone regeneration profiles.
| S-EPMC7683932 | biostudies-literature
Project description:Calcium phosphate-based materials (CaP) have been widely used as bone graft substitutes with a decent osseointegration. However, the mechanism whereby cells function and repair the bone defect in CaP micro-environment is still elusive. The aim of this study is to find the mechanism how osteoclast behaviors mediate bone healing with CaP scaffolds. Recent reports show that behaviors of osteoclast are closely related with osteogenesis, thus we make a hypothesis that active osteoclast behaviors induced by CaP facilitate bone healing. Here, we found a new mechanism that CaP can regulate osteoclast-mediated osseointegration. Calcium phosphate cement (CPC) is selected as a representative CaP. We demonstrate that the osteoclast-mediated osseointegration can be strongly modulated by the stimulation with CaP. An appropriate Ca/P ratio in CaP can effectively promote the RANKL-RANK binding and evoke more activated NF-κB signaling transduction, which results in vigorous osteoclast differentiation. We observe significant improvement of bone healing in vivo, owing to the active coupling effect of osteoclasts. What is more noteworthy is that the phosphate ions released from CaP can be a pivotal role regulating osteoclast activity by changing Ca/P ratio readily in materials. These studies suggest the potential of harnessing osteoclast-mediated osteogenesis in order to develop a materials-manipulated approach for improving osseointegration.
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