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16 pages, 692 KiB  
Systematic Review
Post-Traumatic Segmental Tibial Defects Management: A Systematic Review of the Literature
by Giovanni Marrara, Biagio Zampogna, Viktor Dietrich Schick, Leone Larizza, Paolo Rizzo, Ilaria Sanzarello, Matteo Nanni and Danilo Leonetti
Appl. Sci. 2025, 15(1), 64; https://doi.org/10.3390/app15010064 - 25 Dec 2024
Viewed by 44
Abstract
Introduction: Segmental tibial defects pose significant challenges in orthopedic surgery due to their complexity and high complication rates. This systematic review aimed to evaluate both the effectiveness and outcomes of distraction osteogenesis (D.O.) and the Masquelet technique in treating post-traumatic segmental tibial defects. [...] Read more.
Introduction: Segmental tibial defects pose significant challenges in orthopedic surgery due to their complexity and high complication rates. This systematic review aimed to evaluate both the effectiveness and outcomes of distraction osteogenesis (D.O.) and the Masquelet technique in treating post-traumatic segmental tibial defects. Materials and Methods: A literature search was performed on PubMed, Scopus, and Cochrane. Relevant retrospective and prospective observational studies with a minimum of 12 months follow-up were included. The primary outcome was bone union rate; the secondary outcomes were the type and rate of complications and the clinical and radiological outcomes. Results: Twenty-seven studies met the inclusion criteria, 18 studies reported data on D.O. and 9 on the Masquelet technique. D.O. demonstrated an overall union rate of 79.4% across 422 patients, and the Masquelet technique demonstrated an overall bone union rate of 85% across 113 patients. For D.O., on average, there was one complication per patient, and with the Masquelet technique, there were 0.5 complications per patient. Conclusions: D.O. and the Masquelet technique are the main treatment options for post-traumatic segmental tibial defects. Although union rates are similar, the Masquelet technique showed fewer complications. Treatment choice should consider patient-specific factors and more comparative studies are needed. Full article
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<p>PRISMA flow chart of the literature search.</p>
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21 pages, 1533 KiB  
Article
Treatment of High-Grade Chronic Osteomyelitis and Nonunions with PerOssal®: A Retrospective Analysis of Clinical Efficacy and Patient Perspectives
by Jonas Armbruster, Florian Bussmann, Holger Freischmidt, Gregor Reiter, Paul Alfred Gruetzner and Jan Siad El Barbari
J. Clin. Med. 2024, 13(24), 7764; https://doi.org/10.3390/jcm13247764 - 19 Dec 2024
Viewed by 291
Abstract
Background/Objectives: Traditional autologous bone grafts as a treatment for bone defects have drawbacks like donor-site morbidity and limited supply. PerOssal®, a ceramic bone substitute, may overcome those drawbacks and could offer additional benefits like prolonged, local antibiotic release. This study [...] Read more.
Background/Objectives: Traditional autologous bone grafts as a treatment for bone defects have drawbacks like donor-site morbidity and limited supply. PerOssal®, a ceramic bone substitute, may overcome those drawbacks and could offer additional benefits like prolonged, local antibiotic release. This study investigates the clinical and radiological outcomes, including patient-reported outcomes, of using PerOssal® in nonunions (NU) and high-grade chronic osteomyelitis (COM). Methods: A single-center, retrospective study, investigating patients treated with PerOssal® between January 2020 and December 2023. Collected data include patient characteristics as well as various surgical and outcome parameters including the Lower Extremity Functional Scale (LEFS). Results: A total of 82 patients were analyzed. Reinfection occurred in 19.5% of cases. Osseous integration of PerOssal® was achieved in 89% of cases, higher in cavitary defects (91.5%) than segmental defects (72.7%). The revision rate was 32.9%, mainly due to wound healing disorders and reinfections. Mean LEFS score was 53.4 which was heavily influenced by sex (male: 50.7 vs. female: 63.4), revision surgery (no: 55.7 vs. yes: 49.1), reinfection (no: 56.6 vs. yes: 39.4), and osseous integration of PerOssal® (yes: 55.8 vs. no: 38.4). Conclusions: PerOssal® demonstrates promising outcomes in treating NUs and high-grade COM, especially in cavitary defects, with high osseous integration rates and acceptable functional results. However, reinfection remains a concern, particularly with difficult-to-treat pathogens and extensive surgical histories. Early, comprehensive surgical intervention and tailored antibiotic strategies are essential. Patient selection, defect characteristics, and comorbidities significantly influence success. Further research is needed to optimize treatment protocols. Full article
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<p>LEFS Outcome measurement: (<b>a</b>) mean LEFS score for all localizations (53.4 ± 2.5) and specific localizations of the lower extremity or pelvis. No statistically significant difference was observed; (<b>b</b>) analysis for main drivers for worse LEFS via linear regression showed highest differences in dependence on sex, infection, revision, and failed integration. Accordingly, direct comparison of LEFS showed significantly worse LEFS scores for male patients, patients who had reinfection, or in whom integration of the bone substitute failed. Revision in general lowered the LEFS score but statistical analysis remained non-significant. Medians are the black horizontal lines; interquartile range is the height of the rectangle; minimum and maximum value are the whiskers. LEFS: Lower Extremity Functional Scale; ns = not significant, * = <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Analysis of reinfection: (<b>a</b>) percentage of reinfection in general and split up in between different initial diagnoses; (<b>b</b>) influence of chronic kidney disease on reinfection rate; (<b>c</b>) infection rate in different localizations; (<b>d</b>) mean previous surgeries in patients without and with reinfection. CKD is chronic kidney disease, COM is chronic osteomyelitis, SNU is septic nonunion, ANU is aseptic nonunion; ns = not significant, * = <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Analysis of revision: (<b>a</b>) percentage breakdown of reasons for revision surgeries in general and categorized by the presence or absence of reinfection; (<b>b</b>) impact of bacterial testing on revision rate; (<b>c</b>) Kaplan–Meier survival analysis of PerOssal<sup>®</sup>; (<b>d</b>) average time between index surgery and first revision for different complications; (<b>e</b>) correlation between the number of revision surgeries and the time between the index surgery and the first revision. Black lines indicate linear regression with 95% confidence intervals. WHD is wound healing disorder; ns = not significant; * = <span class="html-italic">p</span> &lt; 0.05.</p>
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<p>Analysis of integration of PerOssal<sup>®</sup> in cavitary defects or consolidation of nonunions after usage of PerOssal<sup>®</sup> in segmental defects: (<b>a</b>) overall percentage across all analyzed patients; (<b>b</b>) percentage in cavitary compared to segmental defects; (<b>c</b>) percentage in patients with and without reinfection. *** = <span class="html-italic">p</span> &lt; 0.001.</p>
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14 pages, 4086 KiB  
Article
3D-Printed Poly(ester urethane)/Poly(3-hydroxybutyrate-co-3-hydroxyvalerate)/Bioglass Scaffolds for Tissue Engineering Applications
by Nayla J. Lores, Beatriz Aráoz, Xavier Hung, Mariano H. Talou, Aldo R. Boccaccini, Gustavo A. Abraham, Élida B. Hermida and Pablo C. Caracciolo
Polymers 2024, 16(23), 3355; https://doi.org/10.3390/polym16233355 - 29 Nov 2024
Viewed by 501
Abstract
Biodegradable polymers and bioceramics give rise to composite structures that serve as scaffolds to promote tissue regeneration. The current research explores the preparation of biodegradable filaments for additive manufacturing. Bioresorbable segmented poly(ester urethanes) (SPEUs) are easily printable elastomers but lack bioactivity and present [...] Read more.
Biodegradable polymers and bioceramics give rise to composite structures that serve as scaffolds to promote tissue regeneration. The current research explores the preparation of biodegradable filaments for additive manufacturing. Bioresorbable segmented poly(ester urethanes) (SPEUs) are easily printable elastomers but lack bioactivity and present low elastic modulus, making them unsuitable for applications such as bone tissue engineering. Strategies such as blending and composite filament production still constitute an important challenge in addressing SPEU limitations. In this work, SPEU-poly(3-hydroxybutyrate-co-3-hydroxyvalerate) (PHBV) blends and SPEU-PHBV-Bioglass 45S5® (BG) composite materials were processed into filaments and 3D structures. A comprehensive characterization of their morphology and thermal and mechanical properties is presented. The production of 3D structures based on SPEU-PHBV with excellent dimensional precision was achieved. Although SPEU-PHBV-BG printed structures showed some defects associated with the printing process, the physicochemical, thermal, and mechanical properties of these materials hold promise. The blend composition, BG content and particle size, processing parameters, and blending techniques were carefully managed to ensure that the mechanical behavior of the material remained under control. The incorporation of PHBV in SPEU-PHBV at 70:30 w/w and BG (5 wt%) acted as reinforcement, enhancing both the elastic modulus of the filaments and the compressive mechanical behavior of the 3D matrices. The compressive stress of the printed scaffold was found to be 1.48 ± 0.13 MPa, which is optimal for tissues such as human proximal tibial trabecular bone. Therefore, these materials show potential for use in the design and manufacture of customized structures for bone tissue engineering. Full article
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<p>SEM micrographs of the cross-sectional views of the filaments: SPEU (<b>A</b>–<b>C</b>), SPEU-PHBV (<b>D</b>–<b>F</b>), and SPEU-PHBV-BG ((<b>G</b>,<b>H</b>,<b>I</b>), BG microparticles in yellow circles) (90×, 250×, and 1000×, respectively).</p>
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<p>SEM micrographs of BG particles: (<b>A</b>–<b>D</b>) (1000×, 2000×, 2500×, and 3000×, respectively).</p>
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<p>TGA curves of (<b>A</b>) PHBV, SPEU, and composite filaments; and (<b>B</b>) printed structures compared with their respective filaments.</p>
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<p>Printed structures of SPEU-PHBV (two layers). (<b>A</b>,<b>B</b>) SEM micrographs (25×, 60×), (<b>C</b>) optical microscope image (10×), and (<b>D</b>) image of the 3D-printed structure (top view, 13 mm diameter).</p>
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<p>Printed structures of SPEU-PHBV (21 layers). SEM micrographs: (<b>A</b>–<b>C</b>) cross-sectional view (55×, 100×, and 150×), (<b>D</b>,<b>E</b>) top view (130×, 60×), and (<b>F</b>) image of the 3D-printed structure (top view, 15 mm diameter).</p>
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<p>Printed structures of SPEU-PHBV-BG (two layers). (<b>A</b>,<b>B</b>) SEM micrographs (15×, 20×) and (<b>C</b>) image of the 3D-printed structure (top view, 13 mm diameter).</p>
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17 pages, 2025 KiB  
Systematic Review
Generative Adversarial Networks (GANs) in the Field of Head and Neck Surgery: Current Evidence and Prospects for the Future—A Systematic Review
by Luca Michelutti, Alessandro Tel, Marco Zeppieri, Tamara Ius, Edoardo Agosti, Salvatore Sembronio and Massimo Robiony
J. Clin. Med. 2024, 13(12), 3556; https://doi.org/10.3390/jcm13123556 - 18 Jun 2024
Viewed by 1339
Abstract
Background: Generative Adversarial Networks (GANs) are a class of artificial neural networks capable of generating content such as images, text, and sound. For several years already, artificial intelligence algorithms have shown promise as tools in the medical field, particularly in oncology. Generative Adversarial [...] Read more.
Background: Generative Adversarial Networks (GANs) are a class of artificial neural networks capable of generating content such as images, text, and sound. For several years already, artificial intelligence algorithms have shown promise as tools in the medical field, particularly in oncology. Generative Adversarial Networks (GANs) represent a new frontier of innovation, as they are revolutionizing artificial content generation, opening opportunities in artificial intelligence and deep learning. Purpose: This systematic review aims to investigate what the stage of development of such technology is in the field of head and neck surgery, offering a general overview of the applications of such algorithms, how they work, and the potential limitations to be overcome in the future. Methods: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines were followed in conducting this study, and the PICOS framework was used to formulate the research question. The following databases were evaluated: MEDLINE, Embase, Cochrane Central Register of Controlled Trials (CENTRAL), Scopus, ClinicalTrials.gov, ScienceDirect, and CINAHL. Results: Out of 700 studies, only 9 were included. Eight applications of GANs in the head and neck region were summarized, including the classification of craniosynostosis, recognition of the presence of chronic sinusitis, diagnosis of radicular cysts in panoramic X-rays, segmentation of craniomaxillofacial bones, reconstruction of bone defects, removal of metal artifacts from CT scans, prediction of the postoperative face, and improvement of the resolution of panoramic X-rays. Conclusions: Generative Adversarial Networks may represent a new evolutionary step in the study of pathology, oncological and otherwise, making the approach to the disease much more precise and personalized. Full article
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<p>(<b>A</b>) Hierarchy between machine learning, deep learning, and artificial neural networks. (<b>B</b>) The composition of an artificial neural network consisting of an input layer (in green), two hidden layers (in blue), and an output layer (in orange) is shown. Each output within the ANN is used as input for the next layer. These artificial intelligence models, to perform the task for which they are trained, require a significant amount of data for the training set, particularly CNNs. In fact, there are studies in the literature that report the size of the data sample analyzed as a limitation. For example, the study conducted by Romeo et al. (2020) showed how the application of radiomic ML to primary tumor lesions has great potential in predicting the lymph node status of patients with oral cavity and oropharynx lesions, but they report how the small sample size is a problem. This is just one of many promising studies in the literature that report a similar impediment in evaluating the effectiveness and accuracy of such artificial intelligence models [<a href="#B10-jcm-13-03556" class="html-bibr">10</a>].</p>
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<p>Basic architecture operation of a GAN.</p>
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<p>PRISMA flowchart of the systematic review process.</p>
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<p>Robvis tool for assessing the risk of bias.</p>
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<p>Different applications of GANs for the head and neck region.</p>
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20 pages, 1041 KiB  
Systematic Review
Reconstruction of Segmental Mandibular Defects with Double-Barrel Fibula Flap and Osseo-Integrated Implants: A Systematic Review
by Saad Khayat, Ángela Sada Urmeneta, Borja González Moure, Diego Fernández Acosta, Marta Benito Anguita, Ana López López, Juan José Verdaguer Martín, Ignacio Navarro Cuéllar, Farzin Falahat and Carlos Navarro Cuéllar
J. Clin. Med. 2024, 13(12), 3547; https://doi.org/10.3390/jcm13123547 - 17 Jun 2024
Viewed by 1259
Abstract
Background: Mandibular defects resulting from oncological treatment pose significant aesthetic and functional challenges due to the involvement of bone and soft tissues. Immediate reconstruction is crucial to address complications such as malocclusion, mandibular deviation, temporomandibular joint (TMJ) changes, and soft tissue retraction. These [...] Read more.
Background: Mandibular defects resulting from oncological treatment pose significant aesthetic and functional challenges due to the involvement of bone and soft tissues. Immediate reconstruction is crucial to address complications such as malocclusion, mandibular deviation, temporomandibular joint (TMJ) changes, and soft tissue retraction. These issues can lead to functional impairments, including difficulties in chewing, swallowing, and speech. The fibula flap is widely used for mandibular reconstruction due to its long bone segment and robust vascular supply, though it may not always provide adequate bone height for optimal dental rehabilitation. This systematic review aims to determine if the double-barreled fibula flap (DBFF) configuration is a viable alternative for mandibular reconstruction and to evaluate the outcomes of dental implants placed in this type of flap. Materials and Methods: This study adhered to the Cochrane Collaboration criteria and PRISMA guidelines and was registered on the International Platform of Registered Systematic Review and Meta-Analysis Protocols Database (INPLASY2023120026). We included clinical studies published in English, Spanish, or French that focused on adult patients undergoing segmental mandibulectomy followed by DBFF reconstruction and dental rehabilitation. Data sources included Medline/PubMed, the Cochrane Library, EMBASE, Scopus, and manual searches. Two reviewers independently screened and selected studies, with discrepancies resolved by a third reviewer. Data extraction captured variables such as publication year, patient demographics, number of implants, follow-up duration, flap survival, implant failure, and aesthetic outcomes. The risk of bias was assessed using the JBI appraisal tool, and the certainty of evidence was evaluated using the GRADE approach. Results: A total of 17 clinical studies were included, evaluating 245 patients and 402 dental implants. The average patient age was 43.7 years, with a mean follow-up period of 34.3 months. Flap survival was high, with a 98.3% success rate and only four flap losses. The implant failure rate was low at 1.74%. Esthetic outcomes were varied, with only three studies using standardized protocols for evaluation. The overall certainty of evidence for flap survival was moderate, low for implant failure, and very low for aesthetics due to the subjective nature of assessments and variability in reporting. Conclusions: The primary limitations of the evidence included in this review are the observational design of the studies, leading to an inherent risk of bias, inconsistency in reporting methods, and imprecision in outcome measures. Additionally, the subjective nature of aesthetic evaluations and the variability in assessment tools further limit the reliability of the findings. The DBFF technique demonstrates excellent outcomes for mandibular reconstruction, with high flap survival and low implant failure rates, making it a viable option for dental rehabilitation. However, the evidence for aesthetic outcomes is less certain, highlighting the need for more rigorous and standardized research. This review supports the DBFF as a good alternative for mandibular reconstruction with successful dental implant integration, although further studies are needed to enhance the reliability of aesthetic evaluations. Full article
(This article belongs to the Special Issue Craniofacial and Reconstructive Plastic Surgery)
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<p>Flowchart for the study selection.</p>
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<p>SCC: squamous cell carcinoma; OS: osteosarcoma; KC: keratocyst; ORN: osteoradionecrosis.</p>
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44 pages, 2422 KiB  
Review
Towards Stem Cell Therapy for Critical-Sized Segmental Bone Defects: Current Trends and Challenges on the Path to Clinical Translation
by Jolene Quek, Catarina Vizetto-Duarte, Swee Hin Teoh and Yen Choo
J. Funct. Biomater. 2024, 15(6), 145; https://doi.org/10.3390/jfb15060145 - 27 May 2024
Cited by 2 | Viewed by 2085
Abstract
The management and reconstruction of critical-sized segmental bone defects remain a major clinical challenge for orthopaedic clinicians and surgeons. In particular, regenerative medicine approaches that involve incorporating stem cells within tissue engineering scaffolds have great promise for fracture management. This narrative review focuses [...] Read more.
The management and reconstruction of critical-sized segmental bone defects remain a major clinical challenge for orthopaedic clinicians and surgeons. In particular, regenerative medicine approaches that involve incorporating stem cells within tissue engineering scaffolds have great promise for fracture management. This narrative review focuses on the primary components of bone tissue engineering—stem cells, scaffolds, the microenvironment, and vascularisation—addressing current advances and translational and regulatory challenges in the current landscape of stem cell therapy for critical-sized bone defects. To comprehensively explore this research area and offer insights for future treatment options in orthopaedic surgery, we have examined the latest developments and advancements in bone tissue engineering, focusing on those of clinical relevance in recent years. Finally, we present a forward-looking perspective on using stem cells in bone tissue engineering for critical-sized segmental bone defects. Full article
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<p>(<b>a</b>) Number of studies published in the last 10 years and (<b>b</b>) their geographical distribution.</p>
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<p>Low-serum/serum-free media supported BM-MSC growth and viability. Comparison of the yield (<b>a</b>,<b>c</b>) and viability (<b>b</b>,<b>d</b>) of BM-MSCs expanded in six different commercially available low-serum/serum-free media at P4 (<b>a</b>,<b>b)</b> and P5 (<b>c</b>,<b>d</b>) (* <span class="html-italic">p</span> &lt; 0.05), Figures are reprinted from Reference [<a href="#B57-jfb-15-00145" class="html-bibr">57</a>], with permission from the authors.</p>
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<p>Rabbit BM-MSCs and bone morphogenetic protein-2 (BMP-2) encapsulated in a chitosan hydrogel in a 3D-printed poly(ε-caprolactone) (PCL) scaffold. (<b>a</b>) (<b>i</b>) Appearance of a 3D PCL scaffold. (<b>ii</b>) SEM images of a PCL scaffold (<b>left</b>) and hybrid scaffold (<b>right</b>). Red rectangle shows the pores of PCL scaffold filled with chitosan gel. Scale bars = 100 μm. (<b>b</b>) (<b>i</b>) A hybrid scaffold of rBM-MSCs encapsulated in a chitosan hydrogel offers similar compressive strength to a PCL scaffold. (<b>ii</b>) CCK-8 assay (<b>left</b>) showed that rBM-MSCs remained viable in a hybrid scaffold with the highest ALP activity (<b>right</b>) (*<sup>,#</sup> <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01). Figures are reprinted from Reference [<a href="#B75-jfb-15-00145" class="html-bibr">75</a>], with permission from the authors.</p>
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<p>Schematic diagram of the development process of a customised design of a 3D-printed polycaprolactone-tricalcium phosphate (PCL-TCP) scaffold for the patient’s defect. Cross-sectional images of a CT scan (<b>A</b>). Based on the CT scan, the surface geometry of a 3D model (<b>B</b>) and patient-specific scaffold (<b>C</b>) are 3D-printed. The figure is reprinted from Reference [<a href="#B185-jfb-15-00145" class="html-bibr">185</a>], with permission from the authors.</p>
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<p>Schematic illustration of (<b>a</b>) an in vivo bioreactor strategy, (<b>b</b>) AV loop-based vascularisation and (<b>c</b>) regenerative matching axial vascularization. Figures are reprinted from (<b>a</b>) Reference [<a href="#B252-jfb-15-00145" class="html-bibr">252</a>], (<b>b</b>) Reference [<a href="#B258-jfb-15-00145" class="html-bibr">258</a>], and (<b>c</b>) Reference [<a href="#B174-jfb-15-00145" class="html-bibr">174</a>], with permission from the authors.</p>
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12 pages, 1779 KiB  
Article
The Impact of Bonding Agents and Bone Defects on the Fracture Resistance of Reattached Vertically Root-Fractured Teeth
by Satheesh B. Haralur, Nasser Mohammed Alshahrani, Saeed Hadi Alafra, Muath Ali Hakami, Omar Abdulaziz AbuMesmar, Mohammed A. Al-Qarni, Saeed M. AlQahtani and Nasser M. Alqahtani
Coatings 2024, 14(6), 661; https://doi.org/10.3390/coatings14060661 - 23 May 2024
Viewed by 1260
Abstract
Many patients experience vertical root fractures, and clinicians often consider conservative treatment options like reattaching the fractured root segments. The study investigated the impact of different bonding agents on the fracture resistance of rebonded vertically fractured teeth with various alveolar bone defects. Human [...] Read more.
Many patients experience vertical root fractures, and clinicians often consider conservative treatment options like reattaching the fractured root segments. The study investigated the impact of different bonding agents on the fracture resistance of rebonded vertically fractured teeth with various alveolar bone defects. Human premolar teeth with a single root were sectioned and reattached using dual-cure resin cement (DCRC), resin-modified glass ionomer (RMGI), and cyanoacrylate. The reattached teeth were then restored with a resin fiber post, composite resin core, and full veneer metal copings. These teeth were embedded in acrylic blocks with angular, V-shaped, and step-shaped bone defects to simulate various alveolar bone conditions. After subjecting the samples to thermal cycling, the fracture resistance was evaluated using a universal testing machine. Teeth samples reattached with RMGI exhibited a higher average fracture resistance. The study also found that DCRC proved to be an effective bonding agent for VRF teeth. However, cyanoacrylate-rebonded teeth exhibited the lowest fracture resistance. The V-shaped defects had a significant impact on the fracture resistance of reattached VRF teeth, with largely unfavorable fractures observed in these cases. Predominantly favorable fractures were observed in the teeth treated with RMGI. The fracture loads in both RMGI and DCRC groups exceeded the expected masticatory load. Full article
(This article belongs to the Special Issue Surface Properties of Dental Materials and Instruments, 2nd Edition)
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<p>Graphical representation of a model for vertical bone defects with varying widths.</p>
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<p>Flowchart of method: sample distribution.</p>
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<p>Teeth samples with cemented metal coping ready for fracture resistance testing.</p>
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<p>Teeth samples bonded with various bonding agents are being tested for their resistance to fracture using a universal testing machine.</p>
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16 pages, 6663 KiB  
Article
Nanofibrous ε-Polycaprolactone Matrices Containing Nano-Hydroxyapatite and Humulus lupulus L. Extract: Physicochemical and Biological Characterization for Oral Applications
by Jaime Villanueva-Lumbreras, Ciro Rodriguez, María Rosa Aguilar, Hamlet Avilés-Arnaut, Geoffrey A. Cordell and Aida Rodriguez-Garcia
Polymers 2024, 16(9), 1258; https://doi.org/10.3390/polym16091258 - 30 Apr 2024
Viewed by 2204
Abstract
Oral bone defects occur as a result of trauma, cancer, infections, periodontal diseases, and caries. Autogenic and allogenic grafts are the gold standard used to treat and regenerate damaged or defective bone segments. However, these materials do not possess the antimicrobial properties necessary [...] Read more.
Oral bone defects occur as a result of trauma, cancer, infections, periodontal diseases, and caries. Autogenic and allogenic grafts are the gold standard used to treat and regenerate damaged or defective bone segments. However, these materials do not possess the antimicrobial properties necessary to inhibit the invasion of the numerous deleterious pathogens present in the oral microbiota. In the present study, poly(ε-caprolactone) (PCL), nano-hydroxyapatite (nHAp), and a commercial extract of Humulus lupulus L. (hops) were electrospun into polymeric matrices to assess their potential for drug delivery and bone regeneration. The fabricated matrices were analyzed using scanning electron microscopy (SEM), tensile analysis, thermogravimetric analysis (TGA), FTIR assay, and in vitro hydrolytic degradation. The antimicrobial properties were evaluated against the oral pathogens Streptococcus mutans, Porphyromonas gingivalis, and Aggregatibacter actinomycetemcomitans. The cytocompatibility was proved using the MTT assay. SEM analysis established the nanostructured matrices present in the three-dimensional interconnected network. The present research provides new information about the interaction of natural compounds with ceramic and polymeric biomaterials. The hop extract and other natural or synthetic medicinal agents can be effectively loaded into PCL fibers and have the potential to be used in oral applications. Full article
(This article belongs to the Section Smart and Functional Polymers)
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<p>SEM micrographs showing the diameter and distribution of the electrospun fibers of PCL, nHAp, and hop extract: (<b>A</b>) PCL; (<b>B</b>) PCL + nHAp; and (<b>C</b>) PCL + nHAp + hop extract. Median fibers were calculated using more than 100 random fiber positions in three different SEM images.</p>
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<p>Thermographs of the analyzed matrices. (<b>A</b>) The blue line is for the PCL matrices, the green line is for the PCL + nHAp matrices, and the red line is for the PCL + nHAp + hop extract matrices; (<b>B</b>) degradation curves of PCL; (<b>C</b>) degradation curves of PCL + nHAp; and (<b>D</b>) degradation curves of PCL + nHAp + hop extract.</p>
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<p>FTIR spectra for the electrospun matrices. (<b>A</b>): comparison between all the samples; (<b>B</b>): FTIR spectrum of PCL; (<b>C</b>): FTIR spectrum of PCL + nHAp; and (<b>D</b>): FTIR spectrum of PCL + nHAp + hop extract. The arrows show the characteristic absorptions of each material and the functional group assignments.</p>
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<p>Electrospun matrices. (<b>A</b>) PCL-only sample, (<b>B</b>) PCL + nHAp + hop extract sample after 8 weeks of immersion in PBS at 37 °C with constant agitation at 120 rpm and a pH of 7.4.</p>
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<p>Graph and inset table showing the mean and standard deviation (±SD) of the percentage viability (<span class="html-italic">N</span> = 4) of the human skin fibroblasts cultured on the electrospun matrices. Distinct lowercase letters after the standard deviation indicate statistically significant differences between the matrice samples (<span class="html-italic">p</span> &lt; 0.05).</p>
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28 pages, 20226 KiB  
Article
Poly(dl-lactide) Polymer Blended with Mineral Phases for Extrusion 3D Printing—Studies on Degradation and Biocompatibility
by Corina Vater, Christian Bräuer, Stefanie Grom, Tatjana Fecht, Tilman Ahlfeld, Max von Witzleben, Anna-Maria Placht, Kathleen Schütz, Jan Marc Schehl, Tobias Wolfram, Frank Reinauer, Martin Scharffenberg, Jakob Wittenstein, Andreas Hoess, Sascha Heinemann, Michael Gelinsky, Günter Lauer and Anja Lode
Polymers 2024, 16(9), 1254; https://doi.org/10.3390/polym16091254 - 30 Apr 2024
Cited by 1 | Viewed by 1665
Abstract
A promising therapeutic option for the treatment of critical-size mandibular defects is the implantation of biodegradable, porous structures that are produced patient-specifically by using additive manufacturing techniques. In this work, degradable poly(DL-lactide) polymer (PDLLA) was blended with different mineral phases with the aim [...] Read more.
A promising therapeutic option for the treatment of critical-size mandibular defects is the implantation of biodegradable, porous structures that are produced patient-specifically by using additive manufacturing techniques. In this work, degradable poly(DL-lactide) polymer (PDLLA) was blended with different mineral phases with the aim of buffering its acidic degradation products, which can cause inflammation and stimulate bone regeneration. Microparticles of CaCO3, SrCO3, tricalcium phosphates (α-TCP, β-TCP), or strontium-modified hydroxyapatite (SrHAp) were mixed with the polymer powder following processing the blends into scaffolds with the Arburg Plastic Freeforming 3D-printing method. An in vitro degradation study over 24 weeks revealed a buffer effect for all mineral phases, with the buffering capacity of CaCO3 and SrCO3 being the highest. Analysis of conductivity, swelling, microstructure, viscosity, and glass transition temperature evidenced that the mineral phases influence the degradation behavior of the scaffolds. Cytocompatibility of all polymer blends was proven in cell experiments with SaOS-2 cells. Patient-specific implants consisting of PDLLA + CaCO3, which were tested in a pilot in vivo study in a segmental mandibular defect in minipigs, exhibited strong swelling. Based on these results, an in vitro swelling prediction model was developed that simulates the conditions of anisotropic swelling after implantation. Full article
(This article belongs to the Special Issue Extrusion of Polymer Blends and Composites)
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<p>Design of 3D-printed porous and bulk scaffolds used for the in vitro analyses of degradation and cytocompatibility, respectively (<b>a</b>), and one of the two implants for the in vivo analysis (<b>b</b>) with approximate dimensions of 29 × 20 × 20 mm (length × width × height). Exact dimensions were dependent on the individual DVT data.</p>
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<p>Dimensional change in 3D-printed porous scaffolds consisting of PDLLA blended with different mineral phases in comparison to pure PDLLA during aging in water over 24 weeks: average scaffold height (<b>a</b>) and diameter (<b>c</b>); average strand width in x- (<b>b</b>) and y-direction (<b>d</b>); (n = 3, mean ± SD, significant differences of PDLLA vs. the blends: * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001). The dotted line in (<b>a</b>,<b>c</b>) represents the dimension according to the scaffold design.</p>
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<p>Scanning electron microscopic images of 3D-printed porous scaffolds consisting of pure PDLLA or PDLLA blended with different mineral phases before (week 0) and after aging in water over 24 weeks; scale bars represent 100 µm (100x) and 20 µm (500x).</p>
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<p>Measurement of pH value (<b>a</b>) and conductivity (<b>b</b>) in the supernatant of 3D-printed porous scaffolds consisting of pure PDLLA or PDLLA blended with different mineral phases during aging in water over 24 weeks; highly significant differences in pH value (<b>c</b>) and conductivity (<b>d</b>) at week 24 (n = 3, mean ± SD, **** <span class="html-italic">p</span> &lt; 0.0001).</p>
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<p>Differential scanning calorimetry of 3D-printed porous scaffolds consisting of pure PDLLA (<b>a</b>) or PDLLA blended with different mineral phases (<b>b</b>–<b>g</b>) before (week 0 (W0)) and at various time points of aging (weeks 2 (W2), 4 (W4), 24 (W24)) in water. The glass transition temperature is in the range of 50–60 °C.</p>
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<p>Measurement of the inherent viscosity of 3D-printed porous scaffolds consisting of pure PDLLA or PDLLA blended with different mineral phases before (week 0 (W0)) and at various time points of aging (weeks 2 (W2), 4 (W4), 24 (W24)) in water (<b>a</b>); differences in viscosity at week 24 (<b>b</b>) (n = 2, mean and minimum as well as maximum value are depicted).</p>
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<p>Cultivation of SAOS-2 cells on 3D-printed bulk scaffolds consisting of PDLLA blended with different mineral phases in comparison to pure PDLLA: total cell number was correlated with the DNA amount measured after cell lysis (<b>a</b>); the number of metabolically active cells was correlated with the cytosolic LDH activity measured after cell lysis (<b>b</b>); the ALP activity as indicator of osteogenic differentiation is shown as specific activity in relation to the cell number (<b>c</b>); for analysis of ALP activity, the cell-seeded samples were cultured in medium with osteogenic supplements; (n = 3, mean ± SD, significant differences of PDLLA vs. the blends: * <span class="html-italic">p</span> &lt; 0.05, ** <span class="html-italic">p</span> &lt; 0.01, *** <span class="html-italic">p</span> &lt; 0.001, **** <span class="html-italic">p</span> &lt; 0.0001).</p>
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<p>Minipig #1: good fit of the scaffold into the segmental mandibular defect as verified by X-ray analysis directly after implantation (<b>a</b>) (dotted lines = osteotomy borders, * = scaffold); examination at 6 weeks postoperation showed a large intraoral dehiscence (<b>b</b>) (arrow = dehiscence/swollen scaffold) due to a swollen scaffold (<b>c</b>–<b>e</b>).</p>
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<p>New bone formation after 0, 2, 4, and 6 months as analyzed by DVT measurement (top view of the defect area containing the reconstruction plate on the right side).</p>
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<p>Anisotropic swelling of 3D-printed porous scaffolds consisting of PDLLA, PDLLA + CaCO<sub>3</sub>, and PDLLA + SrHAp (90:10) in a 3D-printed model for simulation of the situation after implantation in a bone defect (scale bar: 2 mm). Incubation was carried out in cell culture medium at 37 °C.</p>
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<p>Quantitative analysis of anisotropic swelling of 3D-printed porous scaffolds consisting of PDLLA blended with different mineral phases in comparison to pure PDLLA in the 3D-printed degradation model; incubation was carried out in cell culture medium, 0.9% NaCl, or 0.9% NaCl + HCl (pH4.2) at 37 °C: (<b>a</b>) anisotropic quotient, reflecting the ratio of the scaffold widths in the open (channel) direction and in the closed direction (perpendicular to the channel) and (<b>b</b>) the diagonal pore diameters (n = 3, mean ± SD).</p>
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<p>Scaffold fabrication: porous samples for in vitro analysis. Three-dimensional printed porous scaffolds of PDLLA and PDLLA blended with various mineral phases used for the in vitro degradation experiment. Light microscopic images taken at week 0 of the degradation experiment (scaffold dimensions: diameter of 10 mm, height of 5 mm, designed with a strand thickness of 1 mm and pore dimensions in x and y directions of 1.3 mm and 0.6 mm, respectively (diagonal ca. 1.4 mm)).</p>
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<p>Pilot in vivo study. Segmental mandibular defect model used to test individually manufactured scaffolds (<b>a</b>). Surgical procedure: skin incision (<b>b</b>), dissection of soft tissue and periosteum to expose the lower jawbone (<b>c</b>), application of individually produced cutting and drill guides followed by drilling of the holes for fixing the osteosynthesis plate (<b>d</b>), osteotomy (<b>e</b>), application of individually manufactured osteosynthesis plate and PDLLA + CaCO<sub>3</sub> scaffold followed by fixing of the scaffold to the reconstruction plate (<b>f</b>), closing of intra- and extraoral incisions in multilayer fashion (<b>g</b>–<b>i</b>).</p>
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<p>Analysis of cytocompatibility. Fluorescence microscopic images of SAOS-2 cells on 3D-printed bulk scaffolds consisting of pure PDLLA and PDLLA blended with different mineral phases. After seeding, the samples were incubated over 14 days in cell culture medium without osteogenic supplements. Cytoskeletons are stained with Alexa Fluor 488 Phalloidin (green), and cell nuclei are stained with DAPI (blue). Scale bars represent 100 µm.</p>
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<p>Swelling of PDLLA + CaCO<sub>3</sub> in vivo vs. in vitro. Comparison of swelling between native and explanted scaffold of animal #1 (<b>a</b>,<b>b</b>) and swollen PDLLA + CaCO<sub>3</sub> scaffold at the top and at the bottom after 4 weeks of incubation in vitro (<b>c</b>). In contrast to the scaffold explanted from the animal, pores of the in vitro scaffold remained open at both sides due to homogeneous swelling.</p>
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<p>Histological evaluation of the newly formed bone within the defect area 6 month postoperation in sagittal (<b>a</b>,<b>c</b>) and coronar (<b>b</b>,<b>d</b>) direction (Goldner staining). The red dotted area in (<b>b</b>,<b>d</b>) depicts the area between the osteosynthesis plate and the newly formed bone where the implant was originally placed (yellow asterisks = osteosynthesis plate).</p>
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<p>In vitro degradation of PDLLA vs. PDLLA-PGA in terms of pH development. Measurement of pH value in the supernatant of 3D-printed porous scaffolds consisting of PLLA-PGA or PDLLA during aging in water over 24 weeks (n = 3, mean ± SD).</p>
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15 pages, 9865 KiB  
Article
Reconstruction of Segmental Bone Defect in Canine Tibia Model Utilizing Bi-Phasic Scaffold: Pilot Study
by Dae-Won Haam, Chun-Sik Bae, Jong-Min Kim, Sung-Yun Hann, Chang-Min Richard Yim, Hong-Seok Moon and Daniel S. Oh
Int. J. Mol. Sci. 2024, 25(9), 4604; https://doi.org/10.3390/ijms25094604 - 23 Apr 2024
Cited by 1 | Viewed by 1673
Abstract
The reunion and restoration of large segmental bone defects pose significant clinical challenges. Conventional strategies primarily involve the combination of bone scaffolds with seeded cells and/or growth factors to regulate osteogenesis and angiogenesis. However, these therapies face inherent issues related to immunogenicity, tumorigenesis, [...] Read more.
The reunion and restoration of large segmental bone defects pose significant clinical challenges. Conventional strategies primarily involve the combination of bone scaffolds with seeded cells and/or growth factors to regulate osteogenesis and angiogenesis. However, these therapies face inherent issues related to immunogenicity, tumorigenesis, bioactivity, and off-the-shelf transplantation. The biogenic micro-environment created by implanted bone grafts plays a crucial role in initiating the bone regeneration cascade. To address this, a highly porous bi-phasic ceramic synthetic bone graft, composed of hydroxyapatite (HA) and alumina (Al), was developed. This graft was employed to repair critical segmental defects, involving the creation of a 2 cm segmental defect in a canine tibia. The assessment of bone regeneration within the synthetic bone graft post-healing was conducted using scintigraphy, micro-CT, histology, and dynamic histomorphometry. The technique yielded pore sizes in the range of 230–430 μm as primary pores, 40–70 μm as secondary inner microchannels, and 200–400 nm as tertiary submicron surface holes. These three components are designed to mimic trabecular bone networks and to provide body fluid adsorption, diffusion, a nutritional supply, communication around the cells, and cell anchorage. The overall porosity was measured at 82.61 ± 1.28%. Both micro-CT imaging and histological analysis provided substantial evidence of robust bone formation and the successful reunion of the critical defect. Furthermore, an histology revealed the presence of vascularization within the newly formed bone area, clearly demonstrating trabecular and cortical bone formation at the 8-week mark post-implantation. Full article
(This article belongs to the Special Issue Recent Development in Scaffolds for Tissue Engineering)
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<p>Various micro-CT images of HA/Al bi-phasic scaffold with dimensions. (<b>A</b>) Overview of scaffold, (<b>B</b>) interconnected macro-pore structure, (<b>C</b>,<b>D</b>) 3 mm-in-diameter inner cavity structure.</p>
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<p>Interconnected, three different structures in the scaffold body. (<b>A</b>) Interconnected macro-pores with trabecular-like structure, (<b>B</b>) micro-channels that exist inside of each trabecular septum (yellow arrowhead), (<b>C</b>) submicron holes for cells to anchor to that exist on the surface of the trabecular septum (blue arrowhead), (<b>D</b>) pore size distribution.</p>
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<p>SEM observation after sintering (<b>A</b>), X-ray diffraction (XRD) analysis (<b>B</b>), EDS spectra (<b>C</b>), and FT-IR spectra (<b>D</b>) of HA/Al bi-phasic scaffold.</p>
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<p>Surgical procedure. (<b>A</b>,<b>B</b>) creation of a 2 cm segmental defect in the beagle tibia, (<b>C</b>) control without scaffold (blue arrow head pointed 2 cm defect only), (<b>D</b>) experiment subject with HA/Al bi-phasic scaffold implantation (yellow arrow head pointed 2 cm defect filled with scaffold).</p>
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<p>Radiographs of segmental defect site in beagle tibia after 0, 2, 4, 6, and 8 weeks. (<b>A0</b>–<b>A8</b>) negative control without scaffold, (<b>A8-1</b>) reconstructed 3D micro-CT image of the defect site without scaffold at 8 weeks after surgery, (<b>B0</b>–<b>B8</b>) experiment subject treated with HA/Al bi-phasic scaffold, (<b>B8-1</b>) reconstructed 3D micro-CT image of the defect site treated with scaffold at 8 weeks after surgery.</p>
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<p>Scintigraphic evaluation at 0 (<b>A</b>), 4 (<b>B</b>), and 8 weeks (<b>C</b>) after surgery for bone uptake (<b>D</b>) into the HA/Al bi-phasic scaffold that was implanted in the segmental defect site for treatment.</p>
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<p>Complete reunion Micro-CT image of 2 cm segmental defect in the beagle tibia by HA/Al bi-phasic scaffold at 8 weeks after surgery (<b>A</b>). Segmental defect region is denoted with rectangular white dotted line (<b>B</b>).</p>
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<p>Seamless bone regeneration was evidenced from the host bone (gray area, left side of the yellow dotted line) into the HA/Al bi-phasic scaffold area (dark area, right side of the yellow dotted line) (<b>A</b>). Zoomed in bright field image (<b>B</b>). Dynamic histology was performed using alizarin red for 6 weeks (<b>C</b>) and calcein green for 8 weeks after surgery (<b>D</b>).</p>
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<p>Evidence of bone regeneration into macro-pore space and micro-channel of HA/Al bi-phasic scaffold. OB: osteoblast lining cell, RBC: red blood cell, OT: osteoid, Ocy: osteocyte, and BM: new bone matrix.</p>
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<p>Evidence of vascularization in macro-pore space and micro-channel of HA/Al bi-phasic scaffold (<b>A</b>,<b>B</b>). RBC: red blood cell and BM: new bone matrix.</p>
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24 pages, 20720 KiB  
Article
Bone Marrow-Derived Mesenchymal Stem Cell-Laden Nanocomposite Scaffolds Enhance Bone Regeneration in Rabbit Critical-Size Segmental Bone Defect Model
by Elangovan Kalaiselvan, Swapan Kumar Maiti, Shivaraju Shivaramu, Shajahan Amitha Banu, Khan Sharun, Divya Mohan, Sangeetha Palakkara, Sadhan Bag, Monalisa Sahoo, Suresh Ramalingam and Jürgen Hescheler
J. Funct. Biomater. 2024, 15(3), 66; https://doi.org/10.3390/jfb15030066 - 10 Mar 2024
Cited by 2 | Viewed by 2370
Abstract
Bone regeneration poses a significant challenge in the field of tissue engineering, prompting ongoing research to explore innovative strategies for effective bone healing. The integration of stem cells and nanomaterial scaffolds has emerged as a promising approach, offering the potential to enhance regenerative [...] Read more.
Bone regeneration poses a significant challenge in the field of tissue engineering, prompting ongoing research to explore innovative strategies for effective bone healing. The integration of stem cells and nanomaterial scaffolds has emerged as a promising approach, offering the potential to enhance regenerative outcomes. This study focuses on the application of a stem cell-laden nanomaterial scaffold designed for bone regeneration in rabbits. The in vivo study was conducted on thirty-six healthy skeletally mature New Zealand white rabbits that were randomly allocated into six groups. Group A was considered the control, wherein a 15 mm critical-sized defect was created and left as such without any treatment. In group B, this defect was filled with a polycaprolactone–hydroxyapatite (PCL + HAP) scaffold, whereas in group C, a PCL + HAP-carboxylated multiwalled carbon nanotube (PCL + HAP + MWCNT-COOH) scaffold was used. In group D, a PCL + HAP + MWCNT-COOH scaffold was used with local injection of bone morphogenetic protein-2 (BMP-2) on postoperative days 30, 45, and 60. The rabbit bone marrow-derived mesenchymal stem cells (rBMSCs) were seeded onto the PCL + HAP + MWCNT-COOH scaffold by the centrifugal method. In group E, an rBMSC-seeded PCL + HAP + MWCNT-COOH scaffold was used along with the local injection of rBMSC on postoperative days 7, 14, and 21. For group F, in addition to the treatment given to group E, BMP-2 was administered locally on postoperative days 30, 45, and 60. Gross observations, radiological observation, scanning electron microscopic assessment, and histological evaluation study showed that group F displayed the best healing properties, followed by group E, group D, group C, and B. Group A showed no healing with ends blunting minimal fibrous tissue. Incorporating growth factor BMP-2 in tissue-engineered rBMSC-loaded nanocomposite PCL + HAP + MWCNT-COOH construct can augment the osteoinductive and osteoconductive properties, thereby enhancing the healing in a critical-sized bone defect. This novel stem cell composite could prove worthy in the treatment of non-union and delayed union fractures in the near future. Full article
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<p>(<b>A1</b>) Nanocomposite polycaprolactone (PCL) + hydroxyapatite (HAP) scaffold and (<b>B1</b>) nanocomposite PCL + HAP + multiwalled carboxylated carbon nanotube scaffold surgically placed in the critical-sized defect in the radius bone. Scanning electron microscope (SEM) image of PCL + HAP scaffold (<b>A2</b>: 1000× and <b>A3</b>: 2000×). SEM image of PCL + HAP + MWCNT-COOH scaffold (<b>B2</b>: 1000× and <b>B3</b>: 2000×).</p>
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<p>Histogram (mean ± SD) showing (<b>A</b>) pain score and (<b>B</b>) swelling score of various treatment groups at different time intervals. Line graph (mean ± SD) showing (<b>C</b>) exudation score and (<b>D</b>) lameness score of various treatment groups at different time intervals.</p>
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<p>Histogram (mean ± SD) showing (<b>A</b>) serum alkaline phosphatase (IU/L), (<b>B</b>) serum phosphorus concentration (mg/dL), and (<b>C</b>) serum ionized calcium (mg/dL) of various treatment groups at different time intervals.</p>
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<p>(<b>A</b>) Medio-lateral radiographs showing healing status of different groups at various time intervals (pre, day 0, day 30, day 60, and day 90). Histogram (mean ± SD) showing radiographic (<b>B</b>) periosteal reaction score, (<b>C</b>) osteotomy line, and (<b>D</b>) critical-size defect (CSD) filling % score of various treatment groups at different time intervals.</p>
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<p>Scanning electron microscope (SEM) images depicting healed bone tissue samples from different groups on day 90.</p>
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<p>(<b>A</b>) Histopathological images depicting healed bone tissue samples from different groups on day 90, stained with hematoxylin and eosin (H&amp;E) for microscopic analysis (scale bar: 400 µm). (<b>B</b>) Histopathological images depicting healed bone tissue samples from different groups on day 90, stained with Masson’s trichrome for microscopic analysis (scale bar: 400 µm). Histogram (mean ± SD) showing the (<b>C</b>) histopathological score and (<b>D</b>) total histopathological score of various treatment groups on day 90.</p>
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13 pages, 1799 KiB  
Article
The Vascularized Fibula as Salvage Procedure in Extremity Reconstruction: A Retrospective Analysis of Time to Heal and Possible Confounders
by Christian Smolle, Judith C. J. Holzer-Geissler, Patrick Mandal, Jessica Schwaller, Gert Petje, Johannes Rois, Lars-Peter Kamolz and Werner Girsch
Life 2024, 14(3), 318; https://doi.org/10.3390/life14030318 - 28 Feb 2024
Cited by 1 | Viewed by 1331
Abstract
The vascularized fibula transfer is a well-established technique for extremity reconstruction, but operative planning and patient selection remains crucial. Although recently developed techniques for bone reconstruction, such as bone segment transfer, are becoming increasingly popular, bone defects may still require vascularized bone grafts [...] Read more.
The vascularized fibula transfer is a well-established technique for extremity reconstruction, but operative planning and patient selection remains crucial. Although recently developed techniques for bone reconstruction, such as bone segment transfer, are becoming increasingly popular, bone defects may still require vascularized bone grafts under certain circumstances. In this study, 41 cases, 28 (68%) men and 13 (32%) women (median age: 40 years), were retrospectively analyzed. Therapy-specific data (flap vascularity [free vs. pedicled] size in cm and configuration [single- vs. double-barrel], mode of fixation [internal/external]) and potential risk factors were ascertained. Indications for reconstruction were osteomyelitis at host site (n = 23, 55%), pseudarthrosis (n = 8, 20%), congenital deformity (n = 6, 15%), traumatic defect, and giant cell tumor of the bone (n = 2, 5% each). Complete healing occurred in 34 (83%) patients after a median time of 6 months. Confounders for prolonged healing were female gender (p = 0.002), reconstruction in the lower limb (p = 0.011), smoking (p = 0.049), and the use of an external fixator (p = 0.009). Six (15%) patients required secondary limb amputation due to reconstruction failure, and one patient had persistent pseudarthrosis at last follow-up. The only risk factor for amputation assessed via logistic regression analysis was preexisting PAOD (peripheral artery occlusive disease; p = 0.008) The free fibula is a reliable tool for extremity reconstruction in various cases, but time to full osseous integration may exceed six months. Patients should be encouraged to cease smoking as it is a modifiable risk factor. Full article
(This article belongs to the Special Issue Skin, Wound, Plastic Surgery and Hand Surgery)
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<p>Schematic illustration of the fibula flap. The fibula (1) is harvested with the nourishing peroneal vessels (2), and for optimal periosteal perfusion, usually a small muscular cuff (3) is included. If needed, the lateral intermuscular septum with its perforating vessels (4) is harvested with the flap, upon which a skin island (5) can be based. In the case of free fibula transfer, the peroneal vessels are re-anastomosed at the recipient site. In the case of pedicled transfer, the fibula remains in the donor leg and is used for tibial reconstruction. The vascular pedicle is transected either distally or proximally to obtain a proximally or distally pedicled fibula graft.</p>
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<p>Time to heal in months. Censored cases are patients that required secondary amputation of the limb.</p>
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<p>Time to heal in months for male (red) and female (blue) gender. Note that amputations (censored cases) were only performed in male patients.</p>
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<p>Time to heal in non-smokers (blue) and smokers (red).</p>
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<p>Time to heal in upper (blue) and lower (red) limbs. Note that amputations (censored cases) only had to be performed in lower limbs.</p>
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<p>Time to heal in months for patients treated with (red) and without (blue) external fixator. Note that amputations (censored cases) were more frequently performed in patients with external fixator.</p>
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35 pages, 1773 KiB  
Review
Stem Cells and Bone Tissue Engineering
by Xueqin Gao, Joseph J. Ruzbarsky, Jonathan E. Layne, Xiang Xiao and Johnny Huard
Life 2024, 14(3), 287; https://doi.org/10.3390/life14030287 - 21 Feb 2024
Cited by 7 | Viewed by 3803
Abstract
Segmental bone defects that are caused by trauma, infection, tumor resection, or osteoporotic fractures present significant surgical treatment challenges. Host bone autograft is considered the gold standard for restoring function but comes with the cost of harvest site comorbidity. Allograft bone is a [...] Read more.
Segmental bone defects that are caused by trauma, infection, tumor resection, or osteoporotic fractures present significant surgical treatment challenges. Host bone autograft is considered the gold standard for restoring function but comes with the cost of harvest site comorbidity. Allograft bone is a secondary option but has its own limitations in the incorporation with the host bone as well as its cost. Therefore, developing new bone tissue engineering strategies to treat bone defects is critically needed. In the past three decades, the use of stem cells that are delivered with different scaffolds or growth factors for bone tissue engineering has made tremendous progress. Many varieties of stem cells have been isolated from different tissues for use in bone tissue engineering. This review summarizes the progress in using different postnatal stem cells, including bone marrow mesenchymal stem cells, muscle-derived stem cells, adipose-derived stem cells, dental pulp stem cells/periodontal ligament stem cells, periosteum stem cells, umbilical cord-derived stem cells, peripheral blood stem cells, urine-derived stem cells, stem cells from apical papilla, and induced pluripotent stem cells, for bone tissue engineering and repair. This review also summarizes the progress using exosomes or extracellular vesicles that are delivered with various scaffolds for bone repair. The advantages and disadvantages of each type of stem cell are also discussed and explained in detail. It is hoped that in the future, these preclinical results will translate into new regenerative therapies for bone defect repair. Full article
(This article belongs to the Special Issue Research Advances in Bone and Cartilage Tissue Engineering)
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<p>Schematic summary of 12 different stem cells for bone tissue engineering. The graph was created by Xiang Xiao using Figma (<a href="https://www.figma.com" target="_blank">https://www.figma.com</a>, accessed on 11 February 2024).</p>
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12 pages, 8994 KiB  
Case Report
Reconstruction of an Extensive Segmental Radial Shaft Bone Defect by Vascularized 3D-Printed Graft Cage
by Philipp Mommsen, Vincent März, Nicco Krezdorn, Gökmen Aktas, Stephan Sehmisch, Peter Maria Vogt, Tobias Großner and Tarek Omar Pacha
J. Pers. Med. 2024, 14(2), 178; https://doi.org/10.3390/jpm14020178 - 4 Feb 2024
Cited by 3 | Viewed by 2237
Abstract
We report here a 46-year-old male patient with a 14 cm segmental bone defect of the radial shaft after third degree open infected fracture caused by a shrapnel injury. The patient underwent fixed-angle plate osteosynthesis and bone reconstruction of the radial shaft by [...] Read more.
We report here a 46-year-old male patient with a 14 cm segmental bone defect of the radial shaft after third degree open infected fracture caused by a shrapnel injury. The patient underwent fixed-angle plate osteosynthesis and bone reconstruction of the radial shaft by a vascularized 3D-printed graft cage, including plastic coverage with a latissimus dorsi flap and an additional central vascular pedicle. Bony reconstruction of segmental defects still represents a major challenge in musculo-skeletal surgery. Thereby, 3D-printed scaffolds or graft cages display a new treatment option for bone restoration. As missing vascularization sets the limits for the treatment of large-volume bone defects by 3D-printed scaffolds, in the present case, we firstly describe the reconstruction of an extensive radial shaft bone defect by using a graft cage with additional vascularization. Full article
(This article belongs to the Special Issue Personalized Treatment for Musculoskeletal Diseases)
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<p>X-ray images (AP and lateral view) of the right forearm: (<b>a</b>) at the time of admission; (<b>b</b>) after 1st operation; and (<b>c</b>) before bone reconstructive surgery.</p>
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<p>CT-based digital planning view of the scaffold with basic (blue) and locking part (purple), and outer cage aperture for graft vascularization (red frame).</p>
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<p>3D-printed graft cage.</p>
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<p>Intraoperative images: (<b>a</b>) patient’s positioning and setting; (<b>b</b>) palmar and (<b>c</b>) dorsal soft tissues of the right forearm; (<b>d</b>) palmar approach to the forearm and preparation of the cement spacer; (<b>e</b>) Masquelet membrane; (<b>f</b>) palmar fixed-angle plate osteosynthesis of the radial shaft; (<b>g</b>) scaffold filled up with autologous bone graft; (<b>h</b>,<b>i</b>) showing the surgical site after graft insertion.</p>
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<p>Preparation of left-sided latissimus dorsi flap, including vascular serratus arcade (*) and small portion of serratus anterior muscle (#).</p>
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<p>Graft vascularization by embedding vascular pedicle into the scaffold (* vascular serratus arcade; # small portion of serratus anterior muscle).</p>
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<p>Patient’s right forearm after surgical intervention.</p>
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<p>Postoperative X-ray images (AP and lateral view) and digital subtraction angiography (DSA) of the right forearm showing adequate implant position and graft vascularization (red frame).</p>
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<p>Postoperative computer tomography (CT) of the right forearm.</p>
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<p>Patient’s right forearm and elbow function 3 months after surgical intervention.</p>
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<p>X-ray images (AP and lateral view) and computer tomography (CT) of the right forearm 3 months after surgical intervention.</p>
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12 pages, 2553 KiB  
Article
Use of Autologous Bone Graft with Bioactive Glass as a Bone Substitute in the Treatment of Large-Sized Bone Defects of the Femur and Tibia
by Sebastian Findeisen, Niklas Gräfe, Melanie Schwilk, Thomas Ferbert, Lars Helbig, Patrick Haubruck, Gerhard Schmidmaier and Michael Tanner
J. Pers. Med. 2023, 13(12), 1644; https://doi.org/10.3390/jpm13121644 - 24 Nov 2023
Cited by 1 | Viewed by 1600
Abstract
Background: Managing bone defects in non-union surgery remains challenging, especially in cases of large defects exceeding 5 cm in size. Historically, amputation and compound osteosynthesis with a remaining PMMA spacer have been viable and commonly used options. The risk of non-union after fractures [...] Read more.
Background: Managing bone defects in non-union surgery remains challenging, especially in cases of large defects exceeding 5 cm in size. Historically, amputation and compound osteosynthesis with a remaining PMMA spacer have been viable and commonly used options. The risk of non-union after fractures varies between 2% and 30% and is dependent on various factors. Autologous bone grafts from the iliac crest are still considered the gold standard but are limited in availability, prompting consideration of artificial grafts. Objectives: The aims and objectives of the study are as follows: 1. To evaluate the radiological outcome of e.g., the consolidation and thus the stability of the bone (three out of four consolidated cortices/Lane-Sandhu-score of at least 3) by using S53P4-type bioactive glass (BaG) as a substitute material for large-sized bone defects in combination with autologous bone using the RIA technique. 2. To determine noticeable data-points as a base for future studies. Methods: In our clinic, 13 patients received bioactive glass (BaG) as a substitute in non-union therapy to promote osteoconductive aspects. BaG is a synthetic material composed of sodium, silicate, calcium, and phosphate. The primary endpoint of our study was to evaluate the radiological consolidation of bone after one and two years. To assess bone stabilization, we used a modified Lane-Sandhu score, considering only radiological criteria. A bone was considered stabilized if it achieved a minimum score of 3. For full consolidation (all four cortices consolidated), a minimum score of 4 was required. Each bone defect exceeded 5 cm in length, with an average size of 6.69 ± 1.92 cm. Results: The mean follow-up period for patients without final bone consolidation was 34.25 months, with a standard deviation of 14.57 months, a median of 32.00 months and a range of 33 months. In contrast, patients with a fully consolidated non-union had an average follow-up of 20.11 ± 15.69 months and a range of 45 months. Overall, the mean time from non-union surgery to consolidation for patients who achieved final union was 14.91 ± 6.70 months. After one year, six patients (46.2%) achieved complete bone consolidation according to the Lane-Sandhu score. Three patients (23.1%) displayed evident callus formation with expected stability, while three patients (23.1%) did not develop any callus, and one patient only formed a minimal callus with no expected stability. After two years, 9 out of 13 patients (69.2%) had a score of 4. The remaining four patients (30.8%) without expected stability either did not heal within two years or required a revision during that time. Conclusions: Bioactive glass (BaG) in combination with autologous bone (RIA) appears to be a suitable filler material for treating extensive non-unions of the femur and tibia. This approach seems to show non-inferiority to treatment with Tricalcium Phosphate (TCP). To ensure the success of this treatment, it is crucial to validate the procedure through a randomized controlled trial (RCT) with a control group using TCP, which would provide higher statistical power and more reliable results. Full article
(This article belongs to the Special Issue New Concepts in Musculoskeletal Medicine)
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<p>Screening process.</p>
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<p>Modified Lane-Sandhu-score.</p>
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<p>Case of a 55-year-old patient with atrophic nonunion following nail fixation of the proximal femur after subtrochanteric femur fracture (<b>A</b>). After performing Masquelet Step I with debridement of the atrophic bone, a significant bone defect exceeding 5 cm in size was observed (<b>B</b>). To address it, BaG was used as a bone substitute in combination with autologous bone using the RIA (Reamer Irrigator Aspirator) technique (<b>C</b>). At the 1-year follow-up (<b>D</b>), X-rays revealed complete bone consolidation, and ongoing bone remodeling was observed after 2 years (extended follow-up) (<b>E</b>).</p>
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<p>Consolidation final.</p>
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