Application of nano-hydroxyapatite/chitosan scaffolds 
on rat calvarial critical-sized defects: A pilot study

Chatzipetros, Emmanouil; Christopoulos, Panos; Donta, Catherine; Tosios, Konstantinos I.; Tsiambas, Evangelos; Tsiourvas, Dimitris; Kalogirou, Eleni Marina; Tsiklakis, Kostas

doi:10.4317/medoral.22455

Cited by 26 publications

(28 citation statements)

References 40 publications

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“…Some limitations of this study are small sample size, analysis at a single time point after the fracture, and lack of mechanical testing, which need to be addressed in future studies. The material can also be tested using different animal models, e.g., model with a critical-sized bone defect, which is another suitable model to study bone repair 22,62 . Also, the size of the implanted scaffold might have to be revised in the future.…”

Section: Discussionmentioning

confidence: 99%

In vitro and in vivo investigation of osteogenic properties of self-contained phosphate-releasing injectable purine-crosslinked chitosan-hydroxyapatite constructs

Jahan

Manickam

Tabrizian

et al. 2020

Sci Rep

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Bone fracture repair is a multifaceted, coordinated physiological process that requires new bone formation and resorption, eventually returning the fractured bone to its original state. currently, a variety of different approaches are pursued to accelerate the repair of defective bones, which include the use of 'gold standard' autologous bone grafts. However, such grafts may not be readily available, and procedural complications may result in undesired outcomes. considering the ease of use and tremendous customization potentials, synthetic materials may become a more suitable alternative of bone grafts. in this study, we examined the osteogenic potential of guanosine 5′-diphosphate-crosslinked chitosan scaffolds with the incorporation of hydroxyapatite, with or without pyrophosphatase activity, both in vitro and in vivo. First, scaffolds embedded with cells were characterized for cell morphology, viability, and attachment. The cell-laden scaffolds were found to significantly enhance proliferation for up to threefold, double alkaline phosphatase activity and osterix expression, and increase calcium phosphate deposits in vitro. Next, chitosan scaffolds were implanted at the fracture site in a mouse model of intramedullary rod-fixed tibial fracture. Our results showed increased callus formation at the fracture site with the scaffold carrying both hydroxyapatite and pyrophosphatase in comparison to the control scaffolds lacking both pyrophosphatase and hydroxyapatite, or pyrophosphatase alone. these results indicate that the pyrophosphatasehydroxyapatite composite scaffold has a promising capacity to facilitate bone fracture healing. Current therapies for injury-related bone loss rely on the use of bone grafts taken from the patient (autograft) or a donor (allograft) that require extensive restructuring and involve invasive surgical procedures. These procedures include the bone length and axis corrections with the Ilizarov ring fixator 1 , as well as the debridement of the wound to remove any damaged tissues with the Masquelet technique 2. Moreover, grafts are associated with risks of infection, donor-site morbidity, and lack of osseointegration to the host bone 3,4. In order to overcome some of these issues, ceramic-based synthetic bone grafts such as hydroxyapatite (HA) are commonly used in bone repair therapies 5. HA is a calcium phosphate-based biomineral found in bone and is often used as a bone substitute and delivery system 6. Cranioplasty performed with porous-HA prostheses, which were designed with inputs from the surgeons, resulted in minimal adverse response and morbidity rates in 51 patients. Also, the lack of mechanical complications and the optimistic clinical data confirmed the high-level safety and good quality performance in these cranial defect repairs 7. Functional integration of HA macroporous scaffolds implanted in four patients with

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Section: Discussionmentioning

confidence: 99%

In vitro and in vivo investigation of osteogenic properties of self-contained phosphate-releasing injectable purine-crosslinked chitosan-hydroxyapatite constructs

Jahan

Manickam

Tabrizian

et al. 2020

Sci Rep

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“…Alg-nanoHA50 and Alg-nanoHA70) presented an inferior osteogenic activation, whether Alg hydrogel induced the lowest osteogenic activation, in a way similar to control. Previous studies have demonstrated the osteogenic-inducing ability of chitosan/hydroxyapatite composite systems, in bone tissue-related applications [20,66,67]. Notwithstanding, no previous studies have addressed the development and biological evaluation of Alg hydrogels' loading with nanoHA particles at different ratios.…”

Section: Discussionmentioning

confidence: 99%

Alginate-nanohydroxyapatite hydrogel system: Optimizing the formulation for enhanced bone regeneration

Barros

Ferraz

Azeredo

et al. 2019

Materials Science and Engineering: C

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A B S T R A C TCeramic/polymer-based biocomposites have emerged as potential biomaterials to fill, replace, repair or regenerate injured or diseased bone, due to their outstanding features in terms of biocompatibility, bioactivity, injectability, and biodegradability. However, these properties can be dependent on the amount of ceramic component present in the polymer-based composite. Therefore, in the present study, the influence of nanohydroxyapatite content (30 to 70 wt%) on alginate-based hydrogels was studied in order to evaluate the best formulation for maximizing bone tissue regeneration. The composite system was characterized in terms of physic-chemical properties and biological response, with in vitro cytocompatibility assessment with human osteoblastic cells and ex vivo functional evaluation in embryonic chick segmental bone defects. The main morphological characteristics of the alginate network were not affected by the addition of nanohydroxyapatite. However, physic-chemical features, like water-swelling rate, stability at extreme pH values, apatite formation, and Ca 2+ release were nanoHA dose-dependent. Within in vitro cytocompatibility assays it was observed that hydrogels with nanoHA 30% content enhanced osteoblastic cells proliferation and expression of osteogenic transcription factors, while those with higher concentrations (50 and 70%) decreased the osteogenic cell response. Ex vivo data underlined the in vitro findings, revealing an enhanced collagenous deposition, trabecular bone formation and matrix mineralization with Alg-nanoHA30 composition, while compositions with higher nanoHA content induced a diminished bone tissue response.The outcomes of this study indicate that nanohydroxyapatite concentration plays a major role in physicchemical properties and biological response of the composite system and the optimization of the components ratio must be met to maximize bone tissue regeneration.

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“…HA alone or in combination with the other biomaterials was used to accelerate repairing the mandibular defect in animal model [ 39 ]. HA with different particle size were used to treat the defects [ 39 , 40 ]. HA remains for long term on the histological sections, when large particle size was used [ 39 ], while using HA nanoparticles for treatment could not be observed within first weeks after transplantation [ 40 , 41 ].…”

Section: Discussionmentioning

confidence: 99%

Synergic effects of decellularized bone matrix, hydroxyapatite, and extracellular vesicles on repairing of the rabbit mandibular bone defect model

et al. 2020

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Background Extracellular vesicles (ECV) and bone extracellular matrix (ECM) have beneficial effects on the treatment of some pathological conditions. The purpose of this study was to find the synergic effects of decellularized bone (DB) ECM and ECVs on the repair of rabbit. Methods The quality of decellularized sheep bones was confirmed by H&E, Hoechst, DNA quantification, immunohistochemistry, histochemical staining, and scanning electron microscopy (SEM). Osteoblast-derived ECVs were evaluated by internalization test, Transmission electron microscopy, Dynamic light scattering, and flow cytometry for CD9, CD63, CD81 markers. The hydrogel containing DB and hydroxyapatite (HA) with or without ECVs was evaluated for osteoblast functions and bone repair both in vitro and in vivo. Results The data indicated ECM preservation after decellularization as well as cell depletion. In vitro assessments revealed that mineralization and alkaline phosphatase activity did not improve after treatment of MG63 cells by ECVs, while in vivo morphomatrical estimations showed synergic effects of ECVs and DB + HA hydrogels on increasing the number of bone-specific cells and vessel and bone area compared to the control, DB + HA and ECV-treated groups. Conclusions The DB enriched with ECVs can be an ideal scaffold for bone tissue engineering and may provide a suitable niche for bone cell migration and differentiation.

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Application of nano-hydroxyapatite/chitosan scaffolds on rat calvarial critical-sized defects: A pilot study

Cited by 26 publications

References 40 publications

In vitro and in vivo investigation of osteogenic properties of self-contained phosphate-releasing injectable purine-crosslinked chitosan-hydroxyapatite constructs

In vitro and in vivo investigation of osteogenic properties of self-contained phosphate-releasing injectable purine-crosslinked chitosan-hydroxyapatite constructs

Alginate-nanohydroxyapatite hydrogel system: Optimizing the formulation for enhanced bone regeneration

Synergic effects of decellularized bone matrix, hydroxyapatite, and extracellular vesicles on repairing of the rabbit mandibular bone defect model

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