Biomaterials-aided mandibular reconstruction using in vivo bioreactors

Large mandibular defects are clinically challenging to reconstruct due to the complex anatomy of the jaw and the limited availability of appropriate tissue for repair. We envision leveraging current advances in fabrication and biomaterials to create implantable devices that generate bone within the patients themselves suitable for their own specific anatomical pathology. The in vivo bioreactor strategy facilitates the generation of large autologous vascularized bony tissue of customized geometry without the addition of exogenous growth factors or cells. To translate this technology, we investigated its success in reconstructing a mandibular defect of physiologically relevant size in sheep. We fabricated and implanted 3D-printed in vivo bioreactors against rib periosteum and utilized biomaterial-based space maintenance to preserve the native anatomical mandibular structure in the defect site before reconstruction. Nine weeks after bioreactor implantation, the ovine mandibles were repaired with the autologous bony tissue generated from the in vivo bioreactors. We evaluated tissues generated in bioreactors by radiographic, histological, mechanical, and biomolecular assays and repaired mandibles by radiographic and histological assays. Biomaterial-aided mandibular reconstruction was successful in a large superior marginal defect in five of six (83%) sheep. Given that these studies utilized clinically available biomaterials, such as bone cement and ceramic particles, this strategy is designed for rapid human translation to improve outcomes in patients with large mandibular defects.

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Marker for the pre-clinical development of bone substitute materials

Current Directions in Biomedical Engineering ◽

10.1515/cdbme-2017-0151 ◽

2017 ◽

Vol 3 (2) ◽

pp. 711-715

Author(s):

Michael de Wild ◽

Simon Zimmermann ◽

Marcel Obrecht ◽

Michel Dard

Keyword(s):

Bone Graft ◽

Mechanical Stability ◽

Clinical Performance ◽

Ex Vivo ◽

Region Of Interest ◽

Defect Site ◽

Novel Approach ◽

Bone Substitute Materials ◽

Clinical Experiments

AbstractThin mechanically stable Ti-cages have been developed for the in-vivo application as X-ray and histology markers for the optimized evaluation of pre-clinical performance of bone graft materials. A metallic frame defines the region of interest during histological investigations and supports the identification of the defect site. This standardization of the procedure enhances the quality of pre-clinical experiments. Different models of thin metallic frameworks were designed and produced out of titanium by additive manufacturing (Selective Laser Melting). The productibility, the mechanical stability, the handling and suitability of several frame geometries were tested during surgery in artificial and in ex-vivo bone before a series of cages was preclinically investigated in the female Göttingen minipigs model. With our novel approach, a flexible process was established that can be adapted to the requirements of any specific animal model and bone graft testing.

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Design, Fabrication, and Accuracy of a Novel Noncovering Lock-Mechanism Bilateral Patient-Specific Drill Guide Template for Nondeformed and Deformed Thoracic Spines

HSS Journal ® ◽

10.1177/1556331621996331 ◽

2021 ◽

pp. 155633162199633

Author(s):

Mehran Ashouri-Sanjani ◽

Shima Mohammadi-Moghadam ◽

Parisa Azimi ◽

Navid Arjmand

Keyword(s):

Thoracic Spine ◽

Sagittal Plane ◽

Ct Scanning ◽

Entry Point ◽

In Vivo Studies ◽

Patient Specific ◽

Plane Angle ◽

Severe Scoliosis ◽

3D Printed

Background: Pedicle screw (PS) placement has been widely used in fusion surgeries on the thoracic spine. Achieving cost-effective yet accurate placements through nonradiation techniques remains challenging. Questions/Purposes: Novel noncovering lock-mechanism bilateral vertebra-specific drill guides for PS placement were designed/fabricated, and their accuracy for both nondeformed and deformed thoracic spines was tested. Methods: One nondeformed and 1 severe scoliosis human thoracic spine underwent computed tomographic (CT) scanning, and 2 identical proportions of each were 3-dimensional (3D) printed. Pedicle-specific optimal (no perforation) drilling trajectories were determined on the CT images based on the entry point/orientation/diameter/length of each PS. Vertebra-specific templates were designed and 3D printed, assuring minimal yet firm contacts with the vertebrae through a noncovering lock mechanism. One model of each patient was drilled using the freehand and one using the template guides (96 pedicle drillings). Postoperative CT scans from the models with the inserted PSs were obtained and superimposed on the preoperative planned models to evaluate deviations of the PSs. Results: All templates fitted their corresponding vertebra during the simulated operations. As compared with the freehand approach, PS placement deviations from their preplanned positions were significantly reduced: for the nonscoliosis model, from 2.4 to 0.9 mm for the entry point, 5.0° to 3.3° for the transverse plane angle, 7.1° to 2.2° for the sagittal plane angle, and 8.5° to 4.1° for the 3D angle, improving the success rate from 71.7% to 93.5%. Conclusions: These guides are valuable, as the accurate PS trajectory could be customized preoperatively to match the patients’ unique anatomy. In vivo studies will be required to validate this approach.

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Fabrication of 3D-Printed Interpenetrating Hydrogel Scaffolds for Promoting Chondrogenic Differentiation

Polymers ◽

10.3390/polym13132146 ◽

2021 ◽

Vol 13 (13) ◽

pp. 2146

Author(s):

Jian Guan ◽

Fu-zhen Yuan ◽

Zi-mu Mao ◽

Hai-lin Zhu ◽

Lin Lin ◽

...

Keyword(s):

Tissue Engineering ◽

Elastic Modulus ◽

Chondrogenic Differentiation ◽

Marker Genes ◽

Self Healing ◽

Polyethylene Glycol Diacrylate ◽

3D Microenvironment ◽

3D Printed

The limited self-healing ability of cartilage necessitates the application of alternative tissue engineering strategies for repairing the damaged tissue and restoring its normal function. Compared to conventional tissue engineering strategies, three-dimensional (3D) printing offers a greater potential for developing tissue-engineered scaffolds. Herein, we prepared a novel photocrosslinked printable cartilage ink comprising of polyethylene glycol diacrylate (PEGDA), gelatin methacryloyl (GelMA), and chondroitin sulfate methacrylate (CSMA). The PEGDA-GelMA-CSMA scaffolds possessed favorable compressive elastic modulus and degradation rate. In vitro experiments showed good adhesion, proliferation, and F-actin and chondrogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) on the scaffolds. When the CSMA concentration was increased, the compressive elastic modulus, GAG production, and expression of F-actin and cartilage-specific genes (COL2, ACAN, SOX9, PRG4) were significantly improved while the osteogenic marker genes of COL1 and ALP were decreased. The findings of the study indicate that the 3D-printed PEGDA-GelMA-CSMA scaffolds possessed not only adequate mechanical strength but also maintained a suitable 3D microenvironment for differentiation, proliferation, and extracellular matrix production of BMSCs, which suggested this customizable 3D-printed PEGDA-GelMA-CSMA scaffold may have great potential for cartilage repair and regeneration in vivo.

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Midface Reconstruction: Planning and Outcome

Indian Journal of Plastic Surgery ◽

10.1055/s-0040-1721870 ◽

2020 ◽

Vol 53 (03) ◽

pp. 324-334

Author(s):

Gautam Biswas

Keyword(s):

Digital Imaging ◽

3D Structure ◽

Three Dimensional ◽

The Past ◽

Complex Anatomy ◽

Osseointegrated Implants ◽

Low Profile ◽

3D Printed ◽

Midface Reconstruction ◽

Reconstruction Planning

Abstract Reconstruction of the complex anatomy and aesthetics of the midface is often a challenge. A careful understanding of this three-dimensional (3D) structure is necessary. Anticipating the extent of excision and its planning following oncological resections is critical.In the past over two decades, with the advances in microsurgical procedures, contributions toward the reconstruction of this area have generated interest. Planning using digital imaging, 3D printed models, osseointegrated implants, and low-profile plates, has favorably impacted the outcome. However, there are still controversies in the management: to use single composite tissues versus multiple tissues; implants versus autografts; vascularized versus nonvascularized bone; prosthesis versus reconstruction.This article explores the present available options in maxillary reconstruction and outlines the approach in the management garnered from past publications and experiences.

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Three-dimensional printing for heart diseases: clinical application review

Bio-Design and Manufacturing ◽

10.1007/s42242-021-00125-8 ◽

2021 ◽

Author(s):

Yanyan Ma ◽

Peng Ding ◽

Lanlan Li ◽

Yang Liu ◽

Ping Jin ◽

...

Keyword(s):

3D Printing ◽

Clinical Application ◽

Heart Diseases ◽

Three Dimensional ◽

Convincing Evidence ◽

Surgical Interventions ◽

Three Dimensional Printing ◽

Complex Anatomy ◽

Precise Understanding ◽

3D Printed

AbstractHeart diseases remain the top threat to human health, and the treatment of heart diseases changes with each passing day. Convincing evidence shows that three-dimensional (3D) printing allows for a more precise understanding of the complex anatomy associated with various heart diseases. In addition, 3D-printed models of cardiac diseases may serve as effective educational tools and for hands-on simulation of surgical interventions. We introduce examples of the clinical applications of different types of 3D printing based on specific cases and clinical application scenarios of 3D printing in treating heart diseases. We also discuss the limitations and clinically unmet needs of 3D printing in this context.

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Thrombus Imaging Using 3D Printed Middle Cerebral Artery Model and Preclinical Imaging Techniques: Application to Thrombus Targeting and Thrombolytic Studies

Pharmaceutics ◽

10.3390/pharmaceutics12121207 ◽

2020 ◽

Vol 12 (12) ◽

pp. 1207

Author(s):

Andrea Vítečková Wünschová ◽

Adam Novobilský ◽

Jana Hložková ◽

Peter Scheer ◽

Hana Petroková ◽

...

Keyword(s):

Middle Cerebral Artery ◽

Cerebral Artery ◽

Imaging Techniques ◽

Barium Sulphate ◽

Flow Conditions ◽

Preclinical Imaging ◽

Blood Clots ◽

3D Printed

Diseases with the highest burden for society such as stroke, myocardial infarction, pulmonary embolism, and others are due to blood clots. Preclinical and clinical techniques to study blood clots are important tools for translational research of new diagnostic and therapeutic modalities that target blood clots. In this study, we employed a three-dimensional (3D) printed middle cerebral artery model to image clots under flow conditions using preclinical imaging techniques including fluorescent whole-body imaging, magnetic resonance imaging (MRI), and computed X-ray microtomography (microCT). Both liposome-based, fibrin-targeted, and non-targeted contrast agents were proven to provide a sufficient signal for clot imaging within the model under flow conditions. The application of the model for clot targeting studies and thrombolytic studies using preclinical imaging techniques is shown here. For the first time, a novel method of thrombus labeling utilizing barium sulphate (Micropaque®) is presented here as an example of successfully employed contrast agents for in vitro experiments evaluating the time-course of thrombolysis and thus the efficacy of a thrombolytic drug, recombinant tissue plasminogen activator (rtPA). Finally, the proof-of-concept of in vivo clot imaging in a middle cerebral artery occlusion (MCAO) rat model using barium sulphate-labelled clots is presented, confirming the great potential of such an approach to make experiments comparable between in vitro and in vivo models, finally leading to a reduction in animals needed.

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In Vivo Evaluation of 3D-Printed Polycaprolactone Scaffold Implantation Combined with β-TCP Powder for Alveolar Bone Augmentation in a Beagle Defect Model

Materials ◽

10.3390/ma11020238 ◽

2018 ◽

Vol 11 (2) ◽

pp. 238 ◽

Cited By ~ 33

Author(s):

Su Park ◽

Hyo-Jung Lee ◽

Keun-Suh Kim ◽

Sang Lee ◽

Jung-Tae Lee ◽

...

Keyword(s):

Alveolar Bone ◽

Bone Augmentation ◽

Defect Model ◽

In Vivo Evaluation ◽

3D Printed

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Abstract 17070: Engineering a Novel Ex Vivo Heart Simulator for Biomechanical Analysis of the Aortomitral Junction

Circulation ◽

10.1161/circ.142.suppl_3.17070 ◽

2020 ◽

Vol 142 (Suppl_3) ◽

Author(s):

Matthew H Park ◽

Annabel Imbrie-moore ◽

Yuanjia Zhu ◽

Hanjay Wang ◽

Michael J Paulsen ◽

...

Keyword(s):

Cardiac Output ◽

Ex Vivo ◽

Clinical Care ◽

Biomechanical Analysis ◽

Future Experimentation ◽

3D Printed ◽

Biomechanical Changes ◽

Predictive Risk ◽

Future Work

Introduction: Advances in ex vivo heart simulation have enabled the study of valvular biomechanics, disease pathologies, and repair strategies. However, these simulators test the valves in isolation, which does not fully replicate in vivo physiology. We hypothesize that by engineering a simulator that preserves the aortomitral junction, we can better recreate pathophysiologies such as systolic anterior motion (SAM). Here, we present a new heart simulator that preserves and manipulates the native aortomitral physiology. Methods: Our simulator is comprised of three subsystems: the ventricular chamber, atrial chamber, and aortic chamber (Fig A, B). The heart is excised at the apex to preserve the papillary muscles, and the left ventricle, atrial cuff, and aorta are fixed to their respective chambers via hemostatic suturing to 3D-printed elastomeric rings. The chambers are equipped with pressure and flow sensors, and a linear piston pump generates physiologic pressures and flows. The atrial and aortic chambers are mounted on 5-degree-of-freedom arms. To demonstrate system function, we manipulated the aortomitral angle and measured aortic cardiac output. Results: In our testing, we evaluated two unique configurations of an explanted porcine heart, of which the aortomitral angles spanned the SAM predictive risk threshold of <120° (Fig C, D). From the flow readings, we measured a 36% reduction in aortic cardiac output upon decreasing the aortomitral angle by 25°. Conclusions: This work highlights the design and development of an ex vivo heart simulator capable of modeling native aortomitral physiology. Our results point to a clear direction for future experimentation, particularly evaluating the biomechanical changes of the heart based on the aortomitral angle. Future work will utilize this platform to create new models and repair techniques to ultimately improve clinical care of valvular pathologies.

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