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Bone Tissue Engineering: Recent Advances and Translation to Clinical Application
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Bone Tissue Engineering: Recent Advances and Translation to Clinical Application

A special issue of Journal of Functional Biomaterials (ISSN 2079-4983). This special issue belongs to the section "Bone Biomaterials".

Deadline for manuscript submissions: 28 February 2025 | Viewed by 6890

Special Issue Editors

Dr. Fernando Guastaldi

E-Mail Website
Guest Editor
Division of Oral and Maxillofacial Surgery, Department of Surgery, Massachusetts General Hospital, Harvard School of Dental Medicine, Harvard Medical School, Boston, MA, USA
Interests: 3D printing; biomaterials; scaffolds; bone tissue engineering; maxillofacial regeneration; preclinical research; regenerative medicine
Dr. Bhushan Mahadik

E-Mail Website
Guest Editor
Prellis Biologics, San Francisco Bay Area, CA, USA
Interests: 3D printing; stem cell biology; bioreactors; microfluidics; biomaterials; immunology

Special Issue Information

Dear Colleagues,

The treatment and regeneration of large bone defects in the skeleton are complex, pose significant clinical challenges to surgeons and scientists, and impose a tremendous burden on healthcare systems worldwide. Even though bone tissue possesses the unique and intrinsic ability to heal, large bone defects have a limited capacity for spontaneous repair and often experience a poor long-term recovery. Despite innovations in surgical techniques, current clinical strategies for bone defect regeneration demonstrate significant limitations and drawbacks, including donor-site morbidity, the risk of infection, poor anatomical match, insufficient bone volume, higher costs, bone graft resorption, and rejection. In recent decades, advances in computer-assisted planning, three-dimensional (3D) printing technology, and bone tissue engineering (BTE) have offered promising novel treatment alternatives by employing biocompatible scaffold materials, autologous mesenchymal stem cells, and growth factors. Furthermore, the complex signaling cascade of the native immune system plays a crucial role in determining the efficacy and viability of the tissue-engineered implant. It forms an essential component of the BTE strategy. These approaches have provided a new platform for basic and translational research, and have exhibited promising results with regard to large bone regeneration that might profoundly improve patients’ function, form, and quality of life. Thus, 3D printing and BTE strategies are exciting, sustainable, personalized, and minimally invasive alternatives to bone harvesting techniques, and are therefore poised to significantly impact clinical outcomes.

This Special Issue aims to compile the recent advances in bone tissue engineering and their scientific and clinical applications. We welcome original research articles and comprehensive reviews that address the following topics: preclinical research; clinical trials; advances in biomaterials for bone tissue engineering; 3D printing and bioprinting technologies; and scaffold–immune system interactions.

Dr. Fernando Guastaldi
Dr. Bhushan Mahadik
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Functional Biomaterials is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • bone tissue engineering
  • regenerative medicine
  • biomaterials
  • scaffolds
  • 3D printing
  • mesenchymal stem cells
  • growth factors
  • immunological response
  • translational research
  • clinical trials

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Published Papers (4 papers)

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Research

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17 pages, 6847 KiB  
Article
PLLA/GO Scaffolds Filled with Canine Placenta Hydrogel and Mesenchymal Stem Cells for Bone Repair in Goat Mandibles
by Thamires Santos-Silva, Inácio Silva Viana, Andrea Barros Piazzon S. Queiroz, Fabrício Singaretti de Oliveira, Bianca de Oliveira Horvath-Pereira, Leandro Norberto da Silva-Júnior, Michelle Silva Araujo, Paulo Alescio Canola, Luís Gustavo Gosuen G. Dias, Marcelo Melo Soares and Maria Angelica Miglino
J. Funct. Biomater. 2024, 15(10), 311; https://doi.org/10.3390/jfb15100311 - 20 Oct 2024
Viewed by 856
Abstract
Bone defects in animals can arise from various causes, including diseases, neoplasms, and most commonly, trauma. Comminuted fractures that exceed the critical size may heal poorly due to deficient or interrupted vascularization, resulting in an insufficient number of progenitor cells necessary for bone [...] Read more.
Bone defects in animals can arise from various causes, including diseases, neoplasms, and most commonly, trauma. Comminuted fractures that exceed the critical size may heal poorly due to deficient or interrupted vascularization, resulting in an insufficient number of progenitor cells necessary for bone regeneration. In this context, 3D printing techniques using poly-L-lactic acid/graphene oxide (PLLA/GO) aim to address this issue by creating customized scaffolds combined with canine placenta hydrogel and mesenchymal stem cells for use in goat mandibles, compared to a control group using titanium plate fixation. Ten canine placentas were decellularized and characterized using histological techniques. A hydrogel derived from the canine placenta extracellular matrix (cpECM) was produced to improve cell attachment to the scaffolds. In vitro cytotoxicity and cell adhesion to the cpECM hydrogel were assessed by scanning electron microscopy (SEM). The resulting biomaterials, cpECM hydrogel and PLLA/GO scaffolds, maintained their functional structure and supported cell adhesion, maintenance, and proliferation in vitro. Thermography showed that PLLA/GO scaffolds with cpECM hydrogel performed effectively, similar to the control group. Computed tomography scans revealed bone calluses, suggesting an ongoing repair process. These findings demonstrate the innovative technological potential of these materials for use in surgical interventions. Future studies on PLLA/GO scaffolds will provide further insights into their effects on goat models. Full article
(This article belongs to the Special Issue Bone Tissue Engineering: Recent Advances and Translation to Clinical Application)
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13 pages, 2775 KiB  
Article
Optimizing Filament-Based TCP Scaffold Design for Osteoconduction and Bone Augmentation: Insights from In Vivo Rabbit Models
by Julien Guerrero, Ekaterina Maevskaia, Chafik Ghayor, Indranil Bhattacharya and Franz E. Weber
J. Funct. Biomater. 2024, 15(7), 174; https://doi.org/10.3390/jfb15070174 - 25 Jun 2024
Viewed by 1185
Abstract
Additive manufacturing has emerged as a transformative tool in biomedical engineering, offering precise control over scaffold design for bone tissue engineering and regenerative medicine. While much attention has been focused on optimizing pore-based scaffold architectures, filament-based microarchitectures remain relatively understudied, despite the fact [...] Read more.
Additive manufacturing has emerged as a transformative tool in biomedical engineering, offering precise control over scaffold design for bone tissue engineering and regenerative medicine. While much attention has been focused on optimizing pore-based scaffold architectures, filament-based microarchitectures remain relatively understudied, despite the fact that the majority of 3D-printers generate filament-based structures. Here, we investigated the influence of filament characteristics on bone regeneration outcomes using a lithography-based additive manufacturing approach. Three distinct filament-based scaffolds (Fil050, Fil083, and Fil125) identical in macroporosity and transparency, crafted from tri-calcium phosphate (TCP) with varying filament thicknesses and distance, were evaluated in a rabbit model of bone augmentation and non-critical calvarial defect. Additionally, two scaffold types differing in filament directionality (Fil and FilG) were compared to elucidate optimal design parameters. Distance of bone ingrowth and percentage of regenerated area within scaffolds were measured by histomorphometric analysis. Our findings reveal filaments of 0.50 mm as the most effective filament-based scaffold, demonstrating superior bone ingrowth and bony regenerated area compared to larger size filament (i.e., 0.83 mm and 1.25 mm scaffolds). Optimized directionality of filaments can overcome the reduced performance of larger filaments. This study advances our understanding of microarchitecture’s role in bone tissue engineering and holds significant implications for clinical practice, paving the way for the development of highly tailored, patient-specific bone substitutes with enhanced efficacy. Full article
(This article belongs to the Special Issue Bone Tissue Engineering: Recent Advances and Translation to Clinical Application)
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Review

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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 1808
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
(This article belongs to the Special Issue Bone Tissue Engineering: Recent Advances and Translation to Clinical Application)
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35 pages, 8310 KiB  
Review
Biomaterials for Regenerative Cranioplasty: Current State of Clinical Application and Future Challenges
by Lizhe He
J. Funct. Biomater. 2024, 15(4), 84; https://doi.org/10.3390/jfb15040084 - 28 Mar 2024
Viewed by 2417
Abstract
Acquired cranial defects are a prevalent condition in neurosurgery and call for cranioplasty, where the missing or defective cranium is replaced by an implant. Nevertheless, the biomaterials in current clinical applications are hardly exempt from long-term safety and comfort concerns. An appealing solution [...] Read more.
Acquired cranial defects are a prevalent condition in neurosurgery and call for cranioplasty, where the missing or defective cranium is replaced by an implant. Nevertheless, the biomaterials in current clinical applications are hardly exempt from long-term safety and comfort concerns. An appealing solution is regenerative cranioplasty, where biomaterials with/without cells and bioactive molecules are applied to induce the regeneration of the cranium and ultimately repair the cranial defects. This review examines the current state of research, development, and translational application of regenerative cranioplasty biomaterials and discusses the efforts required in future research. The first section briefly introduced the regenerative capacity of the cranium, including the spontaneous bone regeneration bioactivities and the presence of pluripotent skeletal stem cells in the cranial suture. Then, three major types of biomaterials for regenerative cranioplasty, namely the calcium phosphate/titanium (CaP/Ti) composites, mineralised collagen, and 3D-printed polycaprolactone (PCL) composites, are reviewed for their composition, material properties, and findings from clinical trials. The third part discusses perspectives on future research and development of regenerative cranioplasty biomaterials, with a considerable portion based on issues identified in clinical trials. This review aims to facilitate the development of biomaterials that ultimately contribute to a safer and more effective healing of cranial defects. Full article
(This article belongs to the Special Issue Bone Tissue Engineering: Recent Advances and Translation to Clinical Application)
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