Scaffolds for Bone Tissue Engineering

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Biomedical Engineering and Materials".

Deadline for manuscript submissions: closed (15 March 2023) | Viewed by 13060

Special Issue Editors


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Guest Editor
Division of Bioengineering, School of Chemical and Biomedical Engineering, Nanyang Technological University, Singapore, Singapore
Interests: bone tissue engineering; biomaterials; bioreactors technology; 3D printing technology; marine collagen synthesis; effect of the electro-magnetic field in osteogenesis

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Guest Editor
Faculty of Engineering, School of Mechanical, Medical and Process Engineering, Queensland University of Technology, Brisbane, QLD 4000, Australia
Interests: biomaterials; tissue engineering; regenerative medicine; preclinical animal models
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Special Issue Information

Dear Colleagues,

Bone diseases and trauma are on the rise with an aging population, cancers, and sports-related injuries. Bone tissue engineering uses scaffolds with an interconnected porosity to address the need for cell attachments, angiogenesis, nutrients, and waste transport. The scaffolds act as a “home” for cells to proliferate, remodel, and differentiate. The open channels allow cell–cell communications. Over the years, numerous scaffolds ranging from ceramics to 3D-printed bioresorbable scaffolds have been developed, and some have already been used clinically. However, there are still urgent unmet needs in scaffolds for bone tissue engineering. Bone is piezoelectric, and the present scaffolds are far from ideal. While 3D printing has enabled customization of bony defects without a mold, the biomaterial development to go along with new manufacturing methods from nano to macro still faces challenges. The purpose of this Special Issue is to gather updated research work and invite well-known researchers in interdisciplinary field to share different strategies in the future needs of bone tissue engineering scaffolds.

Prof. Dr. Swee Hin Teoh
Prof. Dr. Dietmar W. Hutmacher
Guest Editors

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Keywords

  • bone tissue engineering
  • 3D-printed scaffolds
  • interconnected pores
  • angiogenesis
  • nutrients and waste transportation
  • biocompatibility
  • biodegradation
  • piezoelectric scaffolds
  • nano and macro features

Published Papers (5 papers)

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Research

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21 pages, 2444 KiB  
Article
Histological and Immunohistochemical Characterization of Osteoimmunological Processes in Scaffold-Guided Bone Regeneration in an Ovine Large Segmental Defect Model
by Ronja Finze, Markus Laubach, Mairim Russo Serafini, Ulrich Kneser and Flavia Medeiros Savi
Biomedicines 2023, 11(10), 2781; https://doi.org/10.3390/biomedicines11102781 - 13 Oct 2023
Cited by 1 | Viewed by 946
Abstract
Large-volume bone defect regeneration is complex and demands time to complete. Several regeneration phases with unique characteristics, including immune responses, follow, overlap, and interdepend on each other and, if successful, lead to the regeneration of the organ bone’s form and function. However, during [...] Read more.
Large-volume bone defect regeneration is complex and demands time to complete. Several regeneration phases with unique characteristics, including immune responses, follow, overlap, and interdepend on each other and, if successful, lead to the regeneration of the organ bone’s form and function. However, during traumatic, infectious, or neoplastic clinical cases, the intrinsic bone regeneration capacity may exceed, and surgical intervention is indicated. Scaffold-guided bone regeneration (SGBR) has recently shown efficacy in preclinical and clinical studies. To investigate different SGBR strategies over periods of up to three years, we have established a well-characterized ovine large segmental tibial bone defect model, for which we have developed and optimized immunohistochemistry (IHC) protocols. We present an overview of the immunohistochemical characterization of different experimental groups, in which all ovine segmental defects were treated with a bone grafting technique combined with an additively manufactured medical-grade polycaprolactone/tricalcium phosphate (mPCL-TCP) scaffold. The qualitative dataset was based on osteoimmunological findings gained from IHC analyses of over 350 sheep surgeries over the past two decades. Our systematic and standardized IHC protocols enabled us to gain further insight into the complex and long-drawn-out bone regeneration processes, which ultimately proved to be a critical element for successful translational research. Full article
(This article belongs to the Special Issue Scaffolds for Bone Tissue Engineering)
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17 pages, 67217 KiB  
Article
Alveolar Ridge Augmentation with a Novel Combination of 3D-Printed Scaffolds and Adipose-Derived Mesenchymal Stem Cells—A Pilot Study in Pigs
by Chau Sang Lau, Jasper Chua, Somasundaram Prasadh, Jing Lim, Leonardo Saigo and Bee Tin Goh
Biomedicines 2023, 11(8), 2274; https://doi.org/10.3390/biomedicines11082274 - 16 Aug 2023
Cited by 3 | Viewed by 1645
Abstract
Alveolar ridge augmentation is an important dental procedure to increase the volume of bone tissue in the alveolar ridge before the installation of a dental implant. To meet the high demand for bone grafts for alveolar ridge augmentation and to overcome the limitations [...] Read more.
Alveolar ridge augmentation is an important dental procedure to increase the volume of bone tissue in the alveolar ridge before the installation of a dental implant. To meet the high demand for bone grafts for alveolar ridge augmentation and to overcome the limitations of autogenous bone, allografts, and xenografts, researchers are developing bone grafts from synthetic materials using novel fabrication techniques such as 3D printing. To improve the clinical performance of synthetic bone grafts, stem cells with osteogenic differentiation capability can be loaded into the grafts. In this pilot study, we propose a novel bone graft which combines a 3D-printed polycaprolactone–tricalcium phosphate (PCL-TCP) scaffold with adipose-derived mesenchymal stem cells (AD-MSCs) that can be harvested, processed and implanted within the alveolar ridge augmentation surgery. We evaluated the novel bone graft in a porcine lateral alveolar defect model. Radiographic analysis revealed that the addition of AD-MSCs to the PCL-TCP scaffold improved the bone volume in the defect from 18.6% to 28.7% after 3 months of healing. Histological analysis showed the presence of AD-MSCs in the PCL-TCP scaffold led to better formation of new bone and less likelihood of fibrous encapsulation of the scaffold. Our pilot study demonstrated that the loading of AD-MSCs improved the bone regeneration capability of PCL-TCP scaffolds, and our novel bone graft is suitable for alveolar ridge augmentation. Full article
(This article belongs to the Special Issue Scaffolds for Bone Tissue Engineering)
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14 pages, 2794 KiB  
Article
Eumelanin from the Black Soldier Fly as Sustainable Biomaterial: Characterisation and Functional Benefits in Tissue-Engineered Composite Scaffolds
by Ugo D’Amora, Alessandra Soriente, Alfredo Ronca, Stefania Scialla, Martina Perrella, Paola Manini, Jun Wei Phua, Christoph Ottenheim, Rocco Di Girolamo, Alessandro Pezzella, Maria Grazia Raucci and Luigi Ambrosio
Biomedicines 2022, 10(11), 2945; https://doi.org/10.3390/biomedicines10112945 - 16 Nov 2022
Cited by 8 | Viewed by 3177
Abstract
An optimized extraction protocol for eumelanins from black soldier flies (BSF-Eumel) allows an in-depth study of natural eumelanin pigments, which are a valuable tool for the design and fabrication of sustainable scaffolds. Here, water-soluble BSF-Eumel sub-micrometer colloidal particles were used as bioactive signals [...] Read more.
An optimized extraction protocol for eumelanins from black soldier flies (BSF-Eumel) allows an in-depth study of natural eumelanin pigments, which are a valuable tool for the design and fabrication of sustainable scaffolds. Here, water-soluble BSF-Eumel sub-micrometer colloidal particles were used as bioactive signals for developing a composite biomaterial ink for scaffold preparation. For this purpose, BSF-Eumel was characterized both chemically and morphologically; moreover, biological studies were carried out to investigate the dose-dependent cell viability and its influence on human mesenchymal stem cells (hMSCs), with the aim of validating suitable protocols and to find an optimal working concentration for eumelanin-based scaffold preparation. As proof of concept, 3D printed scaffolds based on methacrylated hyaluronic acid (MEHA) and BSF-Eumel were successfully produced. The scaffolds with and without BSF-Eumel were characterized in terms of their physico-chemical, mechanical and biological behaviours. The results showed that MEHA/BSF-Eumel scaffolds had similar storage modulus values to MEHA scaffolds. In terms of swelling ratio and stability, these scaffolds were able to retain their structure without significant changes over 21 days. Biological investigations demonstrated the ability of the bioactivated scaffolds to support the adhesion, proliferation and osteogenic differentiation of human mesenchymal stem cells. Full article
(This article belongs to the Special Issue Scaffolds for Bone Tissue Engineering)
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16 pages, 3475 KiB  
Article
Clinical Outcomes of 3D-Printed Bioresorbable Scaffolds for Bone Tissue Engineering—A Pilot Study on 126 Patients for Burrhole Covers in Subdural Hematoma
by Emma M. S. Toh, Ashiley A. Thenpandiyan, Aaron S. C. Foo, John J. Y. Zhang, Mervyn J. R. Lim, Chun Peng Goh, Nivedh Dinesh, Srujana V. Vedicherla, Ming Yang, Kejia Teo, Tseng Tsai Yeo and Vincent D. W. Nga
Biomedicines 2022, 10(11), 2702; https://doi.org/10.3390/biomedicines10112702 - 26 Oct 2022
Cited by 7 | Viewed by 2354
Abstract
Burrhole craniostomy is commonly performed for subdural hematoma (SDH) evacuation, but residual scalp depressions are often cosmetically suboptimal for patients. OsteoplugTM, a bioresorbable polycaprolactone burrhole cover, was introduced by the National University Hospital, Singapore, in 2006 to cover these defects, allowing [...] Read more.
Burrhole craniostomy is commonly performed for subdural hematoma (SDH) evacuation, but residual scalp depressions are often cosmetically suboptimal for patients. OsteoplugTM, a bioresorbable polycaprolactone burrhole cover, was introduced by the National University Hospital, Singapore, in 2006 to cover these defects, allowing osseous integration and vascular ingrowth. However, the cosmetic and safety outcomes of OsteoplugTM-C—the latest (2017) iteration, with a chamfered hole for subdural drains—remain unexplored. Data were collected from a single institution from April 2017 to March 2021. Patient-reported aesthetic outcomes (Aesthetic Numeric Analog (ANA)) and quality of life (EQ-5D-3L including Visual Analog Scale (VAS)) were assessed via telephone interviews. Clinical outcomes included SDH recurrence, postoperative infections, and drain complications. OsteoplugTM-C patients had significantly higher satisfaction and quality of life compared to those without a burrhole cover (ANA: 9 [7, 9] vs. 7 [5, 8], p = 0.019; VAS: 85 [75, 90] vs. 70 [50, 80], p = 0.021), and the absence of a burrhole cover was associated with poorer aesthetic outcomes after multivariable adjustment (adjusted OR: 4.55, 95% CI: 1.09–22.68, p = 0.047). No significant differences in other clinical outcomes were observed between OsteoplugTM-C, OsteoplugTM, or no burrhole cover. Our pilot study supports OsteoplugTM-C and its material polycaprolactone as suitable adjuncts to burrhole craniostomy, improving cosmetic outcomes while achieving comparable safety outcomes. Full article
(This article belongs to the Special Issue Scaffolds for Bone Tissue Engineering)
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Review

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30 pages, 2221 KiB  
Review
Scaffold Guided Bone Regeneration for the Treatment of Large Segmental Defects in Long Bones
by Frank Schulze, Annemarie Lang, Janosch Schoon, Georgi I. Wassilew and Johannes Reichert
Biomedicines 2023, 11(2), 325; https://doi.org/10.3390/biomedicines11020325 - 24 Jan 2023
Cited by 6 | Viewed by 4069
Abstract
Bone generally displays a high intrinsic capacity to regenerate. Nonetheless, large osseous defects sometimes fail to heal. The treatment of such large segmental defects still represents a considerable clinical challenge. The regeneration of large bone defects often proves difficult, since it relies on [...] Read more.
Bone generally displays a high intrinsic capacity to regenerate. Nonetheless, large osseous defects sometimes fail to heal. The treatment of such large segmental defects still represents a considerable clinical challenge. The regeneration of large bone defects often proves difficult, since it relies on the formation of large amounts of bone within an environment impedimental to osteogenesis, characterized by soft tissue damage and hampered vascularization. Consequently, research efforts have concentrated on tissue engineering and regenerative medical strategies to resolve this multifaceted challenge. In this review, we summarize, critically evaluate, and discuss present approaches in light of their clinical relevance; we also present future advanced techniques for bone tissue engineering, outlining the steps to realize for their translation from bench to bedside. The discussion includes the physiology of bone healing, requirements and properties of natural and synthetic biomaterials for bone reconstruction, their use in conjunction with cellular components and suitable growth factors, and strategies to improve vascularization and the translation of these regenerative concepts to in vivo applications. We conclude that the ideal all-purpose material for scaffold-guided bone regeneration is currently not available. It seems that a variety of different solutions will be employed, according to the clinical treatment necessary. Full article
(This article belongs to the Special Issue Scaffolds for Bone Tissue Engineering)
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