Custom Repair of Mandibular Bone Defects with 3D Printed Bioceramic Scaffolds

2017 ◽  
Vol 97 (1) ◽  
pp. 68-76 ◽  
Author(s):  
H. Shao ◽  
M. Sun ◽  
F. Zhang ◽  
A. Liu ◽  
Y. He ◽  
...  
Keyword(s):  
Weight Loss ◽  
Alveolar Bone ◽  
Bone Defects ◽  
Linear Shrinkage ◽  
Tris Buffer ◽  
Bone Tissue Regeneration ◽  
3 Dimensional ◽  
Flexural Resistance

Implanting artificial biomaterial implants into alveolar bone defects with individual shape and appropriate mechanical strength is still a challenge. In this study, bioceramic scaffolds, which can precisely match the mandibular defects in macro and micro, were manufactured by the 3-dimensional (3D) printing technique according to the computed tomography (CT) image. To evaluate the stimulatory effect of the material substrate on bone tissue regeneration in situ in a rabbit mandibular alveolar bone defect model, implants made with the newly developed, mechanically strong ~10% Mg-substituted wollastonite (Ca90%Mg10%SiO3; CSi-Mg10) were fabricated, implanted into the bone defects, and compared with implants made with the typical Ca-phosphate and Ca-silicate porous bioceramics, such as β-tricalcium phosphate (TCP), wollastonite (CaSiO3; CSi), and bredigite (Bred). The initial physicochemical tests indicated that although the CSi-Mg10 scaffolds had the largest pore dimension, they had the lowest porosity mainly due to the significant linear shrinkage of the scaffolds during sintering. Compared with the sparingly dissolvable TCP scaffolds (~2% weight loss) and superfast dissolvable (in Tris buffer within 6 wk) pure CSi and Bred scaffolds (~12% and ~14% weight loss, respectively), the CSi-Mg10 exhibited a mild in vitro biodissolution and moderate weight loss of ~7%. In addition, the CSi-Mg10 scaffolds showed a considerable initial flexural strength (31 MPa) and maintained very high flexural resistance during soaking in Tris buffer. The in vivo results revealed that the CSi-Mg10 scaffolds have markedly higher osteogenic capability than those on the TCP, CSi, and Bred scaffolds after 16 wk. These results suggest a promising potential application of customized CSi-Mg10 3D robocast scaffolds in the clinic, especially for repair of alveolar bone defects.

scholarly journals The possibility of healing alveolar bone defects with simvastatin thermosensitive gel: in vitro/in vivo evaluation

2018 ◽  
Vol Volume 12 ◽  
pp. 1997-2003 ◽  
Author(s):  
Hong Ruan ◽  
Youcheng Yu ◽  
Xuehua Guo ◽  
Qian Jiang ◽  
Ying Luo
Keyword(s):  
Alveolar Bone ◽  
Bone Defects ◽  
In Vivo Evaluation ◽  
Thermosensitive Gel

scholarly journals Cellularizing hydrogel-based scaffolds to repair bone tissue: How to create a physiologically relevant micro-environment?

2017 ◽  
Vol 8 ◽  
pp. 204173141771207 ◽  
Author(s):  
Mathieu Maisani ◽  
Daniele Pezzoli ◽  
Olivier Chassande ◽  
Diego Mantovani
Keyword(s):  
Bone Regeneration ◽  
Bone Tissue ◽  
Bone Repair ◽  
Critical Issue ◽  
Bone Defects ◽  
Bone Tissue Regeneration ◽  
Differentiation Potential ◽  
Promising Alternative

Tissue engineering is a promising alternative to autografts or allografts for the regeneration of large bone defects. Cell-free biomaterials with different degrees of sophistication can be used for several therapeutic indications, to stimulate bone repair by the host tissue. However, when osteoprogenitors are not available in the damaged tissue, exogenous cells with an osteoblast differentiation potential must be provided. These cells should have the capacity to colonize the defect and to participate in the building of new bone tissue. To achieve this goal, cells must survive, remain in the defect site, eventually proliferate, and differentiate into mature osteoblasts. A critical issue for these engrafted cells is to be fed by oxygen and nutrients: the transient absence of a vascular network upon implantation is a major challenge for cells to survive in the site of implantation, and different strategies can be followed to promote cell survival under poor oxygen and nutrient supply and to promote rapid vascularization of the defect area. These strategies involve the use of scaffolds designed to create the appropriate micro-environment for cells to survive, proliferate, and differentiate in vitro and in vivo. Hydrogels are an eclectic class of materials that can be easily cellularized and provide effective, minimally invasive approaches to fill bone defects and favor bone tissue regeneration. Furthermore, by playing on their composition and processing, it is possible to obtain biocompatible systems with adequate chemical, biological, and mechanical properties. However, only a good combination of scaffold and cells, possibly with the aid of incorporated growth factors, can lead to successful results in bone regeneration. This review presents the strategies used to design cellularized hydrogel-based systems for bone regeneration, identifying the key parameters of the many different micro-environments created within hydrogels.

scholarly journals Toward Biofabrication of Resorbable Implants Consisting of a Calcium Phosphate Cement and Fibrin—A Characterization In Vitro and In Vivo

2021 ◽  
Vol 22 (3) ◽  
pp. 1218
Author(s):  
Tilman Ahlfeld ◽  
Anja Lode ◽  
Richard Frank Richter ◽  
Winnie Pradel ◽  
Adrian Franke ◽  
...  
Keyword(s):  
Calcium Phosphate ◽  
Delivery System ◽  
Calcium Phosphate Cement ◽  
Alveolar Bone ◽  
Bone Defects ◽  
Cell Delivery ◽  
Fibrin Gel ◽  
Resorbable Implants

Cleft alveolar bone defects can be treated potentially with tissue engineered bone grafts. Herein, we developed novel biphasic bone constructs consisting of two clinically certified materials, a calcium phosphate cement (CPC) and a fibrin gel that were biofabricated using 3D plotting. The fibrin gel was loaded with mesenchymal stromal cells (MSC) derived from bone marrow. Firstly, the degradation of fibrin as well as the behavior of cells in the biphasic system were evaluated in vitro. Fibrin degraded quickly in presence of MSC. Our results showed that the plotted CPC structure acted slightly stabilizing for the fibrin gel. However, with passing time and fibrin degradation, MSC migrated to the CPC surface. Thus, the fibrin gel could be identified as cell delivery system. A pilot study in vivo was conducted in artificial craniofacial defects in Lewis rats. Ongoing bone formation could be evidenced over 12 weeks but the biphasic constructs were not completely osseous integrated. Nevertheless, our results show that the combination of 3D plotted CPC constructs and fibrin as suitable cell delivery system enables the fabrication of novel regenerative implants for the treatment of alveolar bone defects.

scholarly journals Icaritin Enhancing Bone Formation Initiated by Sub-Microstructured Calcium Phosphate Ceramic for Critical Size Defect Repair

2020 ◽  
Vol 7 ◽  
Author(s):  
Haitao Peng ◽  
Jianxiao Li ◽  
Yanan Xu ◽  
Guoyu Lv
Keyword(s):  
Calcium Phosphate ◽  
Bone Formation ◽  
Bone Tissue ◽  
Tissue Regeneration ◽  
Bone Defects ◽  
Bone Tissue Regeneration ◽  
Calcium Phosphate Ceramic ◽  
Dose Dependent

Adequate bone tissue regeneration has been challenging to achieve at critical-sized bone defects caused by disease. Bone tissue engineering using a combination of scaffolds and bioactive factors provides new hope for the treatment of this extreme condition. Icaritin, a herb-derived chemical, has shown its ability to enhance bone formation both in vitro and in vivo, and it has been found that sub-micron surface structure instructs bone formation in calcium phosphate ceramics (CaPs). Here, we evaluated the possibility of using a submicron surface structured CaP ceramic as the carrier of icaritin for bone tissue regeneration in critical-sized bone defects. Icaritin, an herb-derived chemical, was loaded into a submicron surface structured porous calcium phosphate ceramic (Ø12.8 × 3 mm) to get samples with 0, 10, 50, 250, and 1,250 µg icaritin per CaP disc (M0, M10, M50, M250, M1250 groups, respectively). In vitro evaluation with the certain dosages correlated to those released from the samples showed a dose-dependent enhancement of osteogenic differentiation and mineralization of human bone marrow stromal cells with the presence of osteogenic factors in the culture medium, indicating icaritin is an osteopromotive factor. After intramuscular implantation of the samples in dogs for 8 weeks, a dose-dependent of bone formation was seen with enhanced bone formation at the dosage of 50 and 250 µg. To evaluate the in vivo osteogenic potentials of icaritin-containing CaP ceramic scaffolds in the orthopedic site, a 12.8 mm calvarial defect model in rabbits was established. Micro-computed tomography (micro-CT) and histology results at weeks 4, 8 and 12 post-surgery showed more newly formed bone in M250 group, with correspondingly more new vessel ingrowth. The results presented herein suggested that being osteopromotive, icaritin could enhance bone formation initiated by sub-microstructured CaP ceramics and the CaP ceramics scaffold incorporating icaritin is a promising biomaterial for the treatment of critical-sized defect.

scholarly journals An ARF GTPase module promoting invasion and metastasis through regulating phosphoinositide metabolism

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Marisa Nacke ◽  
Emma Sandilands ◽  
Konstantina Nikolatou ◽  
Álvaro Román-Fernández ◽  
Susan Mason ◽  
...  
Keyword(s):  
Metastatic Cancer ◽  
Cellular Responses ◽  
Signalling Pathways ◽  
External Signal ◽  
Phosphoinositide Metabolism ◽  
Invasion And Metastasis ◽  
3 Dimensional

AbstractThe signalling pathways underpinning cell growth and invasion use overlapping components, yet how mutually exclusive cellular responses occur is unclear. Here, we report development of 3-Dimensional culture analyses to separately quantify growth and invasion. We identify that alternate variants of IQSEC1, an ARF GTPase Exchange Factor, act as switches to promote invasion over growth by controlling phosphoinositide metabolism. All IQSEC1 variants activate ARF5- and ARF6-dependent PIP5-kinase to promote PI(3,4,5)P3-AKT signalling and growth. In contrast, select pro-invasive IQSEC1 variants promote PI(3,4,5)P3 production to form invasion-driving protrusions. Inhibition of IQSEC1 attenuates invasion in vitro and metastasis in vivo. Induction of pro-invasive IQSEC1 variants and elevated IQSEC1 expression occurs in a number of tumour types and is associated with higher-grade metastatic cancer, activation of PI(3,4,5)P3 signalling, and predicts long-term poor outcome across multiple cancers. IQSEC1-regulated phosphoinositide metabolism therefore is a switch to induce invasion over growth in response to the same external signal. Targeting IQSEC1 as the central regulator of this switch may represent a therapeutic vulnerability to stop metastasis.

scholarly journals Dual Network Composites of Poly(vinyl alcohol)-Calcium Metaphosphate/Alginate with Osteogenic Ions for Bone Tissue Engineering in Oral and Maxillofacial Surgery

2021 ◽  
Vol 8 (8) ◽  
pp. 107
Author(s):  
Lilis Iskandar ◽  
Lucy DiSilvio ◽  
Jonathan Acheson ◽  
Sanjukta Deb
Keyword(s):  
Tissue Engineering ◽  
Bone Tissue Engineering ◽  
Bone Tissue ◽  
Vinyl Alcohol ◽  
Maxillofacial Surgery ◽  
Bone Defects ◽  
Bone Tissue Regeneration ◽  
Poly Vinyl Alcohol ◽  
Oral And Maxillofacial Surgery

Despite considerable advances in biomaterials-based bone tissue engineering technologies, autografts remain the gold standard for rehabilitating critical-sized bone defects in the oral and maxillofacial (OMF) region. A majority of advanced synthetic bone substitutes (SBS’s) have not transcended the pre-clinical stage due to inferior clinical performance and translational barriers, which include low scalability, high cost, regulatory restrictions, limited advanced facilities and human resources. The aim of this study is to develop clinically viable alternatives to address the challenges of bone tissue regeneration in the OMF region by developing ‘dual network composites’ (DNC’s) of calcium metaphosphate (CMP)—poly(vinyl alcohol) (PVA)/alginate with osteogenic ions: calcium, zinc and strontium. To fabricate DNC’s, single network composites of PVA/CMP with 10% (w/v) gelatine particles as porogen were developed using two freeze–thawing cycles and subsequently interpenetrated by guluronate-dominant sodium alginate and chelated with calcium, zinc or strontium ions. Physicochemical, compressive, water uptake, thermal, morphological and in vitro biological properties of DNC’s were characterised. The results demonstrated elastic 3D porous scaffolds resembling a ‘spongy bone’ with fluid absorbing capacity, easily sculptable to fit anatomically complex bone defects, biocompatible and osteoconductive in vitro, thus yielding potentially clinically viable for SBS alternatives in OMF surgery.

scholarly journals Halofuginone functions as a therapeutic drug for chronic periodontitis in a mouse model

2020 ◽  
Vol 34 ◽  
pp. 205873842097489
Author(s):  
Jiang Wang ◽  
Bo Wang ◽  
Xin Lv ◽  
Yingjie Wang
Keyword(s):  
Alveolar Bone ◽  
Immune Cell ◽  
Critical Role ◽  
Therapeutic Drug ◽  
Mice Model ◽  
T Helper 17 ◽  
Th17 Cell Differentiation ◽  
Tnf Α

Periodontitis is an inflammatory disease caused by host immune response, resulting in a loss of periodontium and alveolar bone. Immune cells, such as T cells and macrophages, play a critical role in the periodontitis onset. Halofuginone, a natural quinazolinone alkaloid, has been shown to possess anti-fibrosis, anti-cancer, and immunomodulatory properties. However, the effect of halofuginone on periodontitis has never been reported. In this study, a ligature-induced mice model of periodontitis was applied to investigate the potential beneficial effect of halofuginone on periodontitis. We demonstrated that the administration of halofuginone significantly reduced the expression levels of pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) in vivo, and markedly suppressed immune cell infiltration into the infected sites. Furthermore, we also observed that halofuginone treatment blocked the T-helper 17 (Th17) cell differentiation in vivo and in vitro. We demonstrated for the first time that halofuginone alleviated the onset of periodontitis through reducing immune responses.

scholarly journals Interaction of periodontitis and orthodontic tooth movement—an in vitro and in vivo study

2021 ◽  
Author(s):  
Birgit Rath-Deschner ◽  
Andressa V. B. Nogueira ◽  
Svenja Beisel-Memmert ◽  
Marjan Nokhbehsaim ◽  
Sigrun Eick ◽  
...  
Keyword(s):  
Alveolar Bone ◽  
Tooth Movement ◽  
Mechanical Strain ◽  
Orthodontic Tooth Movement ◽  
Fusobacterium Nucleatum ◽  
In Vivo Study ◽  
Rt Pcr ◽  
Periodontal Inflammation

Abstract Objectives The aim of this in vitro and in vivo study was to investigate the interaction of periodontitis and orthodontic tooth movement on interleukin (IL)-6 and C-X-C motif chemokine 2 (CXCL2). Materials and methods The effect of periodontitis and/or orthodontic tooth movement (OTM) on alveolar bone and gingival IL-6 and CXCL2 expressions was studied in rats by histology and RT-PCR, respectively. The animals were assigned to four groups (control, periodontitis, OTM, and combination of periodontitis and OTM). The IL-6 and CXCL2 levels were also studied in human gingival biopsies from periodontally healthy and periodontitis subjects by RT-PCR and immunohistochemistry. Additionally, the synthesis of IL-6 and CXCL2 in response to the periodontopathogen Fusobacterium nucleatum and/or mechanical strain was studied in periodontal fibroblasts by RT-PCR and ELISA. Results Periodontitis caused an increase in gingival levels of IL-6 and CXCL2 in the animal model. Moreover, orthodontic tooth movement further enhanced the bacteria-induced periodontal destruction and gingival IL-6 gene expression. Elevated IL-6 and CXCL2 gingival levels were also found in human periodontitis. Furthermore, mechanical strain increased the stimulatory effect of F. nucleatum on IL-6 protein in vitro. Conclusions Our study suggests that orthodontic tooth movement can enhance bacteria-induced periodontal inflammation and thus destruction and that IL-6 may play a pivotal role in this process. Clinical relevance Orthodontic tooth movement should only be performed after periodontal therapy. In case of periodontitis relapse, orthodontic therapy should be suspended until the periodontal inflammation has been successfully treated and thus the periodontal disease is controlled again.

scholarly journals The Role of Pre-Clinical 3-Dimensional Models of Osteosarcoma

2020 ◽  
Vol 21 (15) ◽  
pp. 5499
Author(s):  
Hannah L. Smith ◽  
Stephen A. Beers ◽  
Juliet C. Gray ◽  
Janos M. Kanczler
Keyword(s):  
Three Dimensional ◽  
Chorioallantoic Membrane ◽  
3D Models ◽  
In Ovo ◽  
Future Directions ◽  
3 Dimensional ◽  
In Vivo Animal Models

Treatment for osteosarcoma (OS) has been largely unchanged for several decades, with typical therapies being a mixture of chemotherapy and surgery. Although therapeutic targets and products against cancer are being continually developed, only a limited number have proved therapeutically active in OS. Thus, the understanding of the OS microenvironment and its interactions are becoming more important in developing new therapies. Three-dimensional (3D) models are important tools in increasing our understanding of complex mechanisms and interactions, such as in OS. In this review, in vivo animal models, in vitro 3D models and in ovo chorioallantoic membrane (CAM) models, are evaluated and discussed as to their contribution in understanding the progressive nature of OS, and cancer research. We aim to provide insight and prospective future directions into the potential translation of 3D models in OS.

scholarly journals Biocompatibility and Bone Formation of Flexible, Cotton Wool-like PLGA/Calcium Phosphate Nanocomposites in Sheep

2011 ◽  
Vol 5 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Oliver D Schneider ◽  
Dirk Mohn ◽  
Roland Fuhrer ◽  
Karina Klein ◽  
Käthi Kämpf ◽  
...  
Keyword(s):  
Calcium Phosphate ◽  
Bone Formation ◽  
Antimicrobial Properties ◽  
Drill Hole ◽  
Bone Defects ◽  
Long Bone ◽  
Minimal Amount ◽  
Cotton Wool

Background: The purpose of this preliminary study was to assess the in vivo performance of synthetic, cotton wool-like nanocomposites consisting of a biodegradable poly(lactide-co-glycolide) fibrous matrix and containing either calcium phosphate nanoparticles (PLGA/CaP 60:40) or silver doped CaP nanoparticles (PLGA/Ag-CaP 60:40). Besides its extraordinary in vitro bioactivity the latter biomaterial (0.4 wt% total silver concentration) provides additional antimicrobial properties for treating bone defects exposed to microorganisms. Materials and Methods: Both flexible artificial bone substitutes were implanted into totally 16 epiphyseal and metaphyseal drill hole defects of long bone in sheep and followed for 8 weeks. Histological and histomorphological analyses were conducted to evaluate the biocompatibility and bone formation applying a score system. The influence of silver on the in vivo performance was further investigated. Results: Semi-quantitative evaluation of histology sections showed for both implant materials an excellent biocompatibility and bone healing with no resorption in the adjacent bone. No signs of inflammation were detectable, either macroscopically or microscopically, as was evident in 5 µm plastic sections by the minimal amount of inflammatory cells. The fibrous biomaterials enabled bone formation directly in the centre of the former defect. The area fraction of new bone formation as determined histomorphometrically after 8 weeks implantation was very similar with 20.5 ± 11.2 % and 22.5 ± 9.2 % for PLGA/CaP and PLGA/Ag-CaP, respectively. Conclusions: The cotton wool-like bone substitute material is easily applicable, biocompatible and might be beneficial in minimal invasive surgery for treating bone defects.

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