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  • Review
  • Open Access
50 Citations
9,333 Views
16 Pages

Novel Techniques and Future Perspective for Investigating Critical-Size Bone Defects

  • Elijah Ejun Huang,
  • Ning Zhang,
  • Huaishuang Shen,
  • Xueping Li,
  • Masahiro Maruyama,
  • Takeshi Utsunomiya,
  • Qi Gao,
  • Roberto A. Guzman and
  • Stuart B. Goodman

A critical-size bone defect is a challenging clinical problem in which a gap between bone ends will not heal and will become a nonunion. The current treatment is to harvest and transplant an autologous bone graft to facilitate bone bridging. To devel...

(This article belongs to the Topic Bioreactors for Advanced Cell Culture, (Nano)toxicity, Regenerative Medicine and Organ Bioengineering)
  • Communication
  • Open Access
6 Citations
3,692 Views
16 Pages

Murine iPSC-Loaded Scaffold Grafts Improve Bone Regeneration in Critical-Size Bone Defects

  • Franziska Kessler,
  • Kevin Arnke,
  • Benjamin Eggerschwiler,
  • Yvonne Neldner,
  • Sonja Märsmann,
  • Olivier Gröninger,
  • Elisa A. Casanova,
  • Fabienne A. Weber,
  • Matthias A. König and
  • Simon Tiziani
  • + 3 authors

In certain situations, bones do not heal completely after fracturing. One of these situations is a critical-size bone defect where the bone cannot heal spontaneously. In such a case, complex fracture treatment over a long period of time is required,...

(This article belongs to the Special Issue Frontiers on Induced Pluripotent Stem Cells (iPSCs))
  • Article
  • Open Access
21 Citations
6,686 Views
14 Pages

The Impact of Defect Size on Bone Healing in Critical-Size Bone Defects Investigated on a Rat Femur Defect Model Comparing Two Treatment Methods

  • Andreas Kammerer,
  • Frederik Alexander Hartmann,
  • Christoph Nau,
  • Maximilian Leiblein,
  • Alexander Schaible,
  • Jonas Neijhoft,
  • Dirk Henrich,
  • René Verboket and
  • Maren Janko

Critical-size bone defects up to 25 cm can be treated successfully using the induced membrane technique established by Masquelet. To shorten this procedure, human acellular dermis (HAD) has had success in replacing this membrane in rat models. The ai...

(This article belongs to the Special Issue Biomaterials for Bone Repair and Regeneration)
  • Article
  • Open Access
8 Citations
2,934 Views
16 Pages

Use of Local Melatonin with Xenogeneic Bone Graft to Treat Critical-Size Bone Defects in Rats with Osteoporosis: A Randomized Study

  • Karen Laurene Dalla Costa,
  • Letícia Furtado Abreu,
  • Camila Barreto Tolomei,
  • Rachel Gomes Eleutério,
  • Rosanna Basting,
  • Gabriela Balbinot,
  • Fabrício Mezzomo Collares,
  • Pedro Lopes,
  • Nelio Veiga and
  • Daiane Cristina Peruzzo
  • + 1 author

The aim of this study was to evaluate the effect of local administration of melatonin (MLT) on molecular biomarkers and calvaria bone critical defects in female rats with or without osteoporosis, associated or not with a xenogeneic biomaterial. Forty...

  • Article
  • Open Access
9 Citations
3,124 Views
18 Pages

Experimental Study on Rats with Critical-Size Bone Defects Comparing Effects of Autologous Bone Graft, Equine Bone Substitute Bio-Gen® Alone or in Association with Platelet-Rich Fibrin (PRF)

  • Petru Ciobanu,
  • Mihai Danciu,
  • Andrei Pascu,
  • Ioannis Gardikiotis,
  • Norin Forna,
  • Mihnea Theodor Sirbu,
  • Anca-Elena Calistru,
  • Bogdan Puha,
  • Bogdan Veliceasa and
  • Paul-Dan Sirbu

25 May 2024

Background: A critical-sized bone defect (CsBD) is considered one that will not heal spontaneously and requires reconstruction. This study aims to compare the results of using different bone reconstructive techniques and to study the potential of pla...

(This article belongs to the Special Issue Polymer-Based Biomaterials for Tissue Engineering Applications)
  • Feature Paper
  • Article
  • Open Access
7 Citations
3,947 Views
16 Pages

Hybrid Mineral/Organic Material Induces Bone Bridging and Bone Volume Augmentation in Rat Calvarial Critical Size Defects

  • Marie Dubus,
  • Loïc Scomazzon,
  • Charlotte Ledouble,
  • Julien Braux,
  • Abdelilah Beljebbar,
  • Laurence Van Gulick,
  • Adrien Baldit,
  • Caroline Gorin,
  • Halima Alem and
  • Halima Kerdjoudj
  • + 5 authors

14 September 2022

In craniofacial bone defects, the promotion of bone volume augmentation remains a challenge. Finding strategies for bone regeneration such as combining resorbable minerals with organic polymers would contribute to solving the bone volume roadblock. H...

(This article belongs to the Special Issue Mineralized Tissues Repair and Regeneration)
  • Systematic Review
  • Open Access
1 Citations
1,616 Views
20 Pages

Vascularization and Bone Regeneration with 3D-Printed Composite Scaffolds in Rodent Critical-Size Calvarial Defects: Systematic Review

  • Milda Vitosyte,
  • Melanie Tesing,
  • Sarlota Galinauskaite,
  • Vygandas Rutkunas and
  • Ieva Gendviliene

27 February 2026

Rapid vascularization is essential for bone regeneration in oral and maxillofacial surgery. This systematic review synthesised in vivo evidence on 3D-printed composite scaffolds in rodent critical-size calvarial defects quantified by Microfil perfusi...

(This article belongs to the Special Issue 3D Printed and Biofabricated Bone Biomaterials: Enhancing Bone Repair and Regeneration)
  • Article
  • Open Access
1 Citations
1,542 Views
17 Pages

Novel Soybean Oil-Based 3D Printed Resin Membrane Used for Guided Bone Regeneration in Calvaria Bone Critical-Size Defects: A Microtomographic and Histologic Study in Rats

  • Eduardo Pires Godoy,
  • Letícia Gabriela Artioli,
  • Daniele Botticelli,
  • Fabrizio Nicoletti,
  • Leonardo Dassatti,
  • Mario Bragaglia,
  • Francesca Nanni,
  • Samuel Porfirio Xavier and
  • Erick Ricardo Silva

18 February 2025

Background: Osseointegrated implants are essential for rehabilitating edentulous patients, but critical bone defects remain challenging. Guided bone regeneration (GBR) with barrier membranes is an effective approach. This study evaluated a 3D printed...

(This article belongs to the Section Applied Dentistry and Oral Sciences)
  • Review
  • Open Access
31 Citations
8,735 Views
44 Pages

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...

(This article belongs to the Special Issue Bone Tissue Engineering: Recent Advances and Translation to Clinical Application)
  • Article
  • Open Access
6 Citations
3,330 Views
13 Pages

Dose-Dependent Effects of a Novel Selective EP4 Prostaglandin Receptor Agonist on Treatment of Critical Size Femoral Bone Defects in a Rat Model

  • Corina Vater,
  • Elisabeth Mehnert,
  • Henriette Bretschneider,
  • Julia Bolte,
  • Lisa Findeisen,
  • Lucas-Maximilian Matuszewski and
  • Stefan Zwingenberger

18 November 2021

Difficulties in treating pseudarthrosis and critical bone defects are still evident in physicians’ clinical routines. Bone morphogenetic protein 2 (BMP-2) has shown promising osteoinductive results but also considerable side effects, not unexpected g...

(This article belongs to the Special Issue Bone Tissue Regeneration: Biology and Strategies)
  • Systematic Review
  • Open Access
22 Citations
5,463 Views
34 Pages

Milestones in Mandibular Bone Tissue Engineering: A Systematic Review of Large Animal Models and Critical-Sized Defects

  • Yannick M. Sillmann,
  • Pascal Eber,
  • Elizabeth Orbeta,
  • Frank Wilde,
  • Andrew J. Gross and
  • Fernando P. S. Guastaldi

15 April 2025

Background/Objectives: Mandibular reconstruction following trauma or oncologic resection is crucial for restoring function and aesthetics. While autologous bone grafting remains the gold standard, it presents challenges such as donor site morbidity a...

(This article belongs to the Section Dentistry, Oral Surgery and Oral Medicine)
  • Article
  • Open Access
7 Citations
3,619 Views
13 Pages

A Synergic Strategy: Adipose-Derived Stem Cell Spheroids Seeded on 3D-Printed PLA/CHA Scaffolds Implanted in a Bone Critical-Size Defect Model

  • Gabriela S. Kronemberger,
  • Thiago Nunes Palhares,
  • Alexandre Malta Rossi,
  • Brunno R. F. Verçosa,
  • Suelen C. Sartoretto,
  • Rodrigo Resende,
  • Marcelo J. Uzeda,
  • Adriana T. N. N. Alves,
  • Gutemberg G. Alves and
  • Leandra Santos Baptista
  • + 2 authors

21 November 2023

Bone critical-size defects and non-union fractures have no intrinsic capacity for self-healing. In this context, the emergence of bone engineering has allowed the development of functional alternatives. The aim of this study was to evaluate the capac...

(This article belongs to the Special Issue Feature Papers in Bone Biomaterials)
  • Article
  • Open Access
10 Citations
3,444 Views
16 Pages

The Effect of Low-Intensity Pulsed Ultrasound on Bone Regeneration and the Expression of Osterix and Cyclooxygenase-2 during Critical-Size Bone Defect Repair

  • Darian Volarić,
  • Gordana Žauhar,
  • Jie Chen,
  • Ana Terezija Jerbić Radetić,
  • Hrvoje Omrčen,
  • Antonio Raič,
  • Roko Pirović and
  • Olga Cvijanović Peloza

Low-intensity pulsed ultrasound (LIPUS) is a form of ultrasound that utilizes low-intensity pulsed waves. Its effect on bones that heal by intramembranous ossification has not been sufficiently investigated. In this study, we examined LIPUS and the a...

(This article belongs to the Special Issue Bone Development and Regeneration 3.0)
  • Article
  • Open Access
10 Citations
3,830 Views
20 Pages

3D-Printed Bioactive Scaffold Loaded with GW9508 Promotes Critical-Size Bone Defect Repair by Regulating Intracellular Metabolism

  • Fangli Huang,
  • Xiao Liu,
  • Xihong Fu,
  • Yan Chen,
  • Dong Jiang,
  • Tingxuan Wang,
  • Rongcheng Hu,
  • Xuenong Zou,
  • Hao Hu and
  • Chun Liu

The process of bone regeneration is complicated, and it is still a major clinical challenge to regenerate critical-size bone defects caused by severe trauma, infection, and tumor resection. Intracellular metabolism has been found to play an important...

(This article belongs to the Special Issue Novel 3D Printing Methods and Applications in Biomedicine)
  • Article
  • Open Access
485 Views
16 Pages

Low-Intensity Pulsed Ultrasound Enhances Intramembranous Bone Healing in a Critical-Size Bone Defect of the Rat Calvaria

  • Darian Volarić,
  • Gordana Žauhar,
  • Jie Chen,
  • Ana Terezija Jerbić Radetić,
  • Rok Kostanjšek,
  • Hrvoje Omrčen,
  • Silvije Šegulja,
  • Edi Rođak and
  • Olga Cvijanović Peloza

13 June 2026

Objectives: Low-intensity pulsed ultrasound (LIPUS) has been widely utilized as a biophysical modality accelerating fracture healing, particularly in bones undergoing endochondral ossification. However, its efficacy in facilitating intramembranous os...

(This article belongs to the Special Issue Orthopaedic Trauma and Bone Healing: Recent Advances and Future Perspectives)
  • Article
  • Open Access
16 Citations
4,650 Views
12 Pages

31 July 2020

Here we evaluated the efficacy of bone repair using various native bovine biomaterials (refined hydroxyapatite (HA), demineralised bone matrix (DBM), and purified bone collagen (COLL)) as compared with commercially available bone mineral and bone aut...

(This article belongs to the Section Biomaterials)
  • Article
  • Open Access
13 Citations
3,317 Views
16 Pages

Preventive Moderate Continuous Running-Exercise Conditioning Improves the Healing of Non-Critical Size Bone Defects in Male Wistar Rats: A Pilot Study Using µCT

  • Céline Bourzac,
  • Morad Bensidhoum,
  • Mathieu Manassero,
  • Christine Chappard,
  • Nicolas Michoux,
  • Stéphane Pallu and
  • Hugues Portier

24 November 2020

Although physical exercise has unquestionable benefits on bone health, its effects on bone healing have been poorly investigated. This study evaluated the effects of preemptive moderate continuous running on the healing of non-critical sized bone def...

(This article belongs to the Special Issue Impact of Physical Exercises on Bone Activities)
  • Article
  • Open Access
643 Views
18 Pages

Dipyridamole-Coated 3D-Printed β-Tricalcium Phosphate Scaffolds: Spectrophotometric Characterization, Drug Release Kinetics, and In Vitro Evaluation to Guide Critical-Sized Bone Defect Repair Studies

  • Purva Rasane,
  • Vasudev Vivekanand Nayak,
  • Lahiru Chamara Weerasinghe Arachchige,
  • Eleni Rice,
  • Zeinab Fotouhi Ashin,
  • Bharath Venkatesan,
  • Venu Varanasi,
  • Noriaki Ono,
  • Simon Young and
  • Lukasz Witek

Critical-sized bone defects remain a significant clinical challenge, and dipyridamole (DIPY)-coated 3D-tricalcium phosphate (β-TCP) scaffolds have shown promising osteogenic efficacy in preclinical models. However, the literature on the systemat...

(This article belongs to the Special Issue Engineering Regeneration: Biomaterials, Biology, and Translation)
  • Article
  • Open Access
2 Citations
2,156 Views
23 Pages

Experimental Early Stimulation of Bone Tissue Neo-Formation for Critical Size Elimination Defects in the Maxillofacial Region

  • Nadezhda Nicolaevna Patlataya,
  • Igor Nicolaevich Bolshakov,
  • Anatoliy Alexandrovich Levenets,
  • Nadezhda Nicolaevna Medvedeva,
  • Vladimir Alexeevich Khorzhevskii and
  • Mariya Arturovna Cherkashina

26 October 2023

A biomaterial is proposed for closing extensive bone defects in the maxillofacial region. The composition of the biomaterial includes high-molecular chitosan, chondroitin sulfate, hyaluronate, heparin, alginate, and inorganic nanostructured hydroxyap...

(This article belongs to the Special Issue Chitosan-Based Coatings for Food, Pharmaceutical and Medical Applications)
  • Article
  • Open Access
1 Citations
2,453 Views
18 Pages

Background/Objectives: Obliterates such as autologous bone dust (BD) or the synthetic bioactive glass S53P4 (BA) are frequently used for the obliteration of non-critical size defects (NCSDs), especially in otosurgery. Both obliterates have advantages...

  • Article
  • Open Access
12 Citations
3,601 Views
13 Pages

Repair of Critical Size Bone Defects Using Synthetic Hydroxyapatite or Xenograft with or without the Bone Marrow Mononuclear Fraction: A Histomorphometric and Immunohistochemical Study in Rat Calvaria

  • Jorge Luís da Silva Pires,
  • Jorge José de Carvalho,
  • Mario José dos Santos Pereira,
  • Igor da Silva Brum,
  • Ana Lucia Rosa Nascimento,
  • Paulo Gonçalo Pinto dos Santos,
  • Lucio Frigo and
  • Ricardo Guimaraes Fischer

26 May 2021

Bone defects are a challenging clinical situation, and the development of hydroxyapatite-based biomaterials is a prolific research field that, in addition, can be joined by stem cells and growth factors in order to deal with the problem. This study c...

(This article belongs to the Section Biomaterials)
  • Article
  • Open Access
7 Citations
3,615 Views
21 Pages

Free Transplantation of a Tissue Engineered Bone Graft into an Irradiated, Critical-Size Femoral Defect in Rats

  • Ulrike Rottensteiner-Brandl,
  • Ulf Bertram,
  • Lara F. Lingens,
  • Katrin Köhn,
  • Luitpold Distel,
  • Tobias Fey,
  • Carolin Körner,
  • Raymund E. Horch and
  • Andreas Arkudas

31 August 2021

Healing of large bone defects remains a challenge in reconstructive surgery, especially with impaired healing potential due to severe trauma, infection or irradiation. In vivo studies are often performed in healthy animals, which might not accurately...

(This article belongs to the Special Issue Cellular Mechanisms of Bone Regeneration)
  • Article
  • Open Access
14 Citations
5,478 Views
16 Pages

Photocrosslinked Dextran-Based Hydrogels as Carrier System for the Cells and Cytokines Induce Bone Regeneration in Critical Size Defects in Mice

  • Ulrike Ritz,
  • Marc Eberhardt,
  • Anja Klein,
  • Petra Frank,
  • Hermann Götz,
  • Alexander Hofmann,
  • Pol Maria Rommens and
  • Ulrich Jonas

20 July 2018

Modified biomaterials have for years been the focus of research into establishing new bone substitutes. In our preceding in vitro study employing different cell cultures, we developed chemically and mechanically characterized hydrogels based on photo...

(This article belongs to the Special Issue Polysaccharide Hydrogels)
  • Article
  • Open Access
14 Citations
3,945 Views
17 Pages

Functionalized 3D-Printed PLA Biomimetic Scaffold for Repairing Critical-Size Bone Defects

  • Xiao Liu,
  • Jianpeng Gao,
  • Xiang Cui,
  • Shaobo Nie,
  • Xiaoyong Wu,
  • Licheng Zhang,
  • Peifu Tang,
  • Jianheng Liu and
  • Ming Li

The treatment of critical-size bone defects remains a complicated clinical challenge. Recently, bone tissue engineering has emerged as a potential therapeutic approach for defect repair. This study examined the biocompatibility and repair efficacy of...

(This article belongs to the Section Biomedical Engineering and Biomaterials)
  • Article
  • Open Access
657 Views
12 Pages

BMP-2-Loaded Self-Crosslinking CaP/Hydrogel Composite Enables Complete Regeneration of Critical-Sized Segmental Bone Defects

  • Amadou Touré,
  • Ombeline Aroux,
  • Joelle Veziers,
  • Sophie Sourice,
  • Kevin Minier,
  • Borhane Fellah,
  • Valérie Geoffroy,
  • Bernard Giumelli,
  • Olivier Gauthier and
  • Pierre Weiss

Critical-size segmental bone defects remain a major challenge in orthopedic surgery, often requiring complex reconstruction strategies associated with significant morbidity. This study evaluated the regenerative potential of a self-crosslinking bone...

(This article belongs to the Special Issue Advanced Technologies for Orthopedic Repair and Regeneration)
  • Article
  • Open Access
12 Citations
3,285 Views
12 Pages

Repair of Rat Calvarial Critical-Sized Defects Using Heparin-Conjugated Fibrin Hydrogel Containing BMP-2 and Adipose-Derived Pericytes

  • Gulshakhar Kudaibergen,
  • Sholpan Mukhlis,
  • Ainur Mukhambetova,
  • Assel Issabekova,
  • Aliya Sekenova,
  • Madina Sarsenova,
  • Abay Temirzhan,
  • Murat Baidarbekov,
  • Baurzhan Umbayev and
  • Vyacheslav Ogay

The repair of critical-sized calvarial defects is a challenging problem for orthopedic surgery. One of the promising strategies of bone bioengineering to enhance the efficacy of large bone defect regeneration is the combined delivery of stem cells wi...

(This article belongs to the Special Issue Bone Tissue Engineering and Translational Research)
  • Article
  • Open Access
4 Citations
2,917 Views
8 Pages

Histological Bone-Healing Evaluation of Critical-Size Defects Filled with β-Tricalcium Phosphate in Rat Tibiae

  • Ana Maria Veiga Vasques,
  • Carlos Roberto Emerenciano Bueno,
  • Maria Rosa Felix de Souza Gomide Guimarães,
  • Diego Valentim,
  • Ana Cláudia Rodrigues da Silva,
  • Francine Benetti,
  • João Miguel Marques Santos,
  • Luciano Tavares Angelo Cintra and
  • Eloi Dezan Junior

30 April 2024

Bone defects may be a result of different pathologies and represent a challenge in different fields of dentistry. Techniques for the correction of bone defects involving the use of several types of grafts have been proposed. This study evaluated bone...

(This article belongs to the Special Issue Advances in Oral Rehabilitation: Materials, Techniques and Clinical Applications)
  • Review
  • Open Access
66 Citations
7,293 Views
26 Pages

The Impact of Bioceramic Scaffolds on Bone Regeneration in Preclinical In Vivo Studies: A Systematic Review

  • Giulia Brunello,
  • Sourav Panda,
  • Lucia Schiavon,
  • Stefano Sivolella,
  • Lisa Biasetto and
  • Massimo Del Fabbro

25 March 2020

Bioceramic scaffolds are appealing for alveolar bone regeneration, because they are emerging as promising alternatives to autogenous and heterogenous bone grafts. The aim of this systematic review is to answer to the focal question: in critical-sized...

(This article belongs to the Special Issue Bioactive Ceramics and Their Applications)
  • Article
  • Open Access
10 Citations
3,497 Views
14 Pages

Treatment of Critical-Size Femoral Bone Defects with Chitosan Scaffolds Produced by a Novel Process from Textile Engineering

  • Bruno Zwingenberger,
  • Corina Vater,
  • Roland L. Bell,
  • Julia Bolte,
  • Elisabeth Mehnert,
  • Ronny Brünler,
  • Dilbar Aibibu and
  • Stefan Zwingenberger

The purpose of this study was to investigate, in vitro and in vivo, the suitability of chitosan (CHS) scaffolds produced by the net-shape-nonwoven (NSN) technology, for use as bone graft substitutes in a critical-size femoral bone defect in rats. For...

(This article belongs to the Section Biomedical Materials and Nanomedicine)
  • Article
  • Open Access
15 Citations
4,565 Views
14 Pages

Spongostan™ Leads to Increased Regeneration of a Rat Calvarial Critical Size Defect Compared to NanoBone® and Actifuse

  • Dirk Wähnert,
  • Julian Koettnitz,
  • Madlen Merten,
  • Daniel Kronenberg,
  • Richard Stange,
  • Johannes F. W. Greiner,
  • Christian Kaltschmidt,
  • Thomas Vordemvenne and
  • Barbara Kaltschmidt

14 April 2021

Bone substitute materials are becoming increasingly important in oral and maxillofacial surgery. Reconstruction of critical size bone defects is still challenging for surgeons. Here, we compared the clinically applied organic bone substitute material...

(This article belongs to the Section Biomaterials)
  • Article
  • Open Access
8 Citations
2,846 Views
12 Pages

Polylevolysine and Fibronectin-Loaded Nano-Hydroxyapatite/PGLA/Dextran-Based Scaffolds for Improving Bone Regeneration: A Histomorphometric in Animal Study

  • Elena Canciani,
  • Paola Straticò,
  • Vincenzo Varasano,
  • Claudia Dellavia,
  • Chiara Sciarrini,
  • Lucio Petrizzi,
  • Lia Rimondini and
  • Elena M. Varoni

The regeneration of large bone defects is still demanding, requiring biocompatible scaffolds, with osteoconductive and osteoinductive properties. This study aimed to assess the pre-clinical efficacy of a nano-hydroxyapatite (nano-HA)/PGLA/dextran-bas...

(This article belongs to the Special Issue Biomaterials for Bone Tissue Engineering 4.0)
  • Feature Paper
  • Article
  • Open Access
2 Citations
1,728 Views
18 Pages

Natural Nacre-Derived Biomimetic Materials for In Vivo Bone Regeneration

  • Pierre-Yves Collart-Dutilleul,
  • Naveen Fatima,
  • Richard Younes,
  • Frédéric Cuisinier,
  • Véronique Barragan-Montero and
  • Alban Desoutter

Bone regeneration in critical-size defects requires biomaterials that provide both structural support and appropriate osteoinductive cues. Natural nacre contains an organic matrix rich in acidic macromolecules with reported osteogenic activity; howev...

(This article belongs to the Special Issue Biomimetic Strategies to Enhance Bone Tissue Healing, Remodeling and Regeneration: 2nd Edition)
  • Article
  • Open Access
19 Citations
3,391 Views
12 Pages

Conditioned Media from Human Pulp Stem Cell Cultures Improve Bone Regeneration in Rat Calvarial Critical-Size Defects

  • Leonardo Fernandes Buss,
  • Gustavo Sigrist de Martin,
  • Elizabeth Ferreira Martinez,
  • Isabela Amanda de Abreu Araújo Porcaro Filgueiras,
  • José Luiz Magnabosco,
  • Bruno Frenhan Alves,
  • Bruno de Macedo Almeida,
  • Tatiana Kotaka,
  • Marcelo Lucchesi Teixeira and
  • André Antonio Pelegrine
  • + 5 authors

The aim of this study was to test whether lyophilized conditioned media from human dental pulp mesenchymal stem cell cultures promote the healing of critical-size defects created in the calvaria of rats. Prior to the surgical procedure, the medium in...

  • Article
  • Open Access
3 Citations
2,809 Views
15 Pages

Evaluation of Two Alloplastic Biomaterials in a Critical-Size Rat Calvarial Defect Model

  • Amanda Finger Stadler,
  • Marta Liliana Musskopf,
  • Vishal Gohel,
  • Jonathan Reside,
  • Eric Everett,
  • Patricia Miguez and
  • Cristiano Susin

Aim: to evaluate the bone regeneration capacity of two alloplastic biomaterials in a critical-size rat calvarial defect model. Methods: A total of 80 rats were randomized into 8 groups of 10 animals each. An Ø8 mm, critical-size calvarial defe...

(This article belongs to the Special Issue Dental Biomaterials in Implantology and Orthodontics)
  • Article
  • Open Access
29 Citations
4,878 Views
13 Pages

Hesperidin Promotes Osteogenesis and Modulates Collagen Matrix Organization and Mineralization In Vitro and In Vivo

  • Patricia A. Miguez,
  • Stephen A. Tuin,
  • Adam G. Robinson,
  • Joyce Belcher,
  • Prapaporn Jongwattanapisan,
  • Kimberly Perley,
  • Vinicius de Paiva Gonҫalves,
  • Arash Hanifi,
  • Nancy Pleshko and
  • Elisabeth R. Barton

This study evaluated the direct effect of a phytochemical, hesperidin, on pre-osteoblast cell function as well as osteogenesis and collagen matrix quality, as there is little known about hesperidin’s influence in mineralized tissue formation and rege...

(This article belongs to the Special Issue Osteoblast Differentiation and Activity in Skeletal Diseases)
  • Systematic Review
  • Open Access
10 Citations
2,882 Views
30 Pages

How Does Ceramic-Based Scaffold Microarchitecture Impact Maxillofacial Bone Regeneration? A Systematic Review of Large Animal Models

  • Ana M. P. Baggio,
  • Yannick M. Sillmann,
  • Pascal Eber,
  • Felicia R. S. Michallek,
  • Joao L. G. C. Monteiro,
  • Ana P. F. Bassi and
  • Fernando P. S. Guastaldi

19 June 2025

Critical-sized bone defects (CSBDs) are injuries that exceed the body’s natural capacity for repair and require external intervention. These defects are particularly challenging in the mandible, often resulting from trauma, tumor resection, or...

(This article belongs to the Special Issue Advanced Biomaterials and Dynamic Scaffolding in Regenerative Medicine)
  • Article
  • Open Access
18 Citations
4,754 Views
13 Pages

Bone Regeneration of Critical-Size Calvarial Defects in Rats Using Highly Pressed Nano-Apatite/Collagen Composites

  • Wataru Hatakeyama,
  • Masayuki Taira,
  • Tomofumi Sawada,
  • Miki Hoshi,
  • Yuki Hachinohe,
  • Hirotaka Sato,
  • Kyoko Takafuji,
  • Hidemichi Kihara,
  • Shinji Takemoto and
  • Hisatomo Kondo

8 May 2022

Osteo-conductive bone substitute materials are required in dentistry. In this study, highly pressed nano-hydroxyapatite/collagen (P-nHAP/COL) composites were formed by a hydraulic press. Critical-size bone defects (Φ = 6 mm) were made in the cran...

(This article belongs to the Special Issue Dental Implant Biomaterials: In Vitro and In Vivo Simulations and Applications)
  • Article
  • Open Access
538 Views
14 Pages

Effect of Additively Manufactured Sphene Ceramic Scaffolds on Bone Response in Rat Critical-Size Calvarial Defects

  • Giulia Brunello,
  • Hamada Elsayed,
  • Lucia Schiavon,
  • Elia Sbettega,
  • Giovanna Iezzi,
  • Barbara Zavan,
  • Simone Carmignato,
  • Enrico Bernardo,
  • Lisa Biasetto and
  • Stefano Sivolella

24 March 2026

Silica-based bioceramics are promising bone substitutes with tunable degradation and mechanical properties. We aimed to assess bone response in critical-size calvarial defects in rats, empty or filled with 3D-printed sphene ceramic (CaTiSiO5) scaffol...

(This article belongs to the Special Issue Innovative Techniques and Materials in Implant Dentistry)
  • Article
  • Open Access
9 Citations
3,269 Views
13 Pages

3 May 2021

Bone regeneration using beta-tricalcium phosphate (β-TCP) can be practiced using a biocomposite scaffold. Poly(ethylene-co-vinylalcohol)/poly(δ-valerolactone)/β-tricalcium phosphate (PEVAV/β-TCP) composite scaffolds showed promising in vitro results....

(This article belongs to the Section Biomaterials)
  • Review
  • Open Access
69 Citations
7,658 Views
28 Pages

16 September 2021

The implementation of a powder bed selective laser processing (PBSLP) technique for bioactive ceramics, including selective laser sintering and melting (SLM/SLS), a laser powder bed fusion (L-PBF) approach is far more challenging when compared to its...

(This article belongs to the Special Issue Laser Processing for Composite Materials)
  • Article
  • Open Access
34 Citations
7,449 Views
19 Pages

Metformin-Incorporated Gelatin/Nano-Hydroxyapatite Scaffolds Promotes Bone Regeneration in Critical Size Rat Alveolar Bone Defect Model

  • Chih-Hsiang Fang,
  • Chung-Kai Sun,
  • Yi-Wen Lin,
  • Min-Chih Hung,
  • Hung-Ying Lin,
  • Ching-Hung Li,
  • I-Ping Lin,
  • Hung-Chen Chang,
  • Jui-Sheng Sun and
  • Jenny Zwei-Chieng Chang

In this study, we fabricated gelatin/nano-hydroxyapatite/metformin scaffold (GHMS) and compared its effectiveness in bone regeneration with extraction-only, Sinbone, and Bio-Oss Collagen® groups in a critical size rat alveolar bone defect model....

(This article belongs to the Special Issue Bone Development and Regeneration 2.0)
  • Review
  • Open Access
915 Views
37 Pages

Bone loss represents a significant clinical burden that has driven the development of improved orthopedic graft substitutes. Although current grafting options, including autografts, allografts, and xenografts, have demonstrated considerable therapeut...

(This article belongs to the Special Issue Functional Scaffolds for Hard Tissue Engineering and Surgery)
  • Article
  • Open Access
53 Citations
4,331 Views
16 Pages

Bacterial Cellulose-Modified Polyhydroxyalkanoates Scaffolds Promotes Bone Formation in Critical Size Calvarial Defects in Mice

  • Ada Codreanu,
  • Cornel Balta,
  • Hildegard Herman,
  • Coralia Cotoraci,
  • Ciprian Valentin Mihali,
  • Nicoleta Zurbau,
  • Catalin Zaharia,
  • Maria Rapa,
  • Paul Stanescu and
  • Anca Hermenean
  • + 4 authors

21 March 2020

Bone regeneration is a claim challenge in addressing bone defects with large tissue deficits, that involves bone grafts to support the activity. In vitro biocompatibility of the bacterial cellulose-modified polyhydroxyalkanoates (PHB/BC) scaffolds an...

(This article belongs to the Special Issue Advanced Nanosciences Applied in Tissue Engineering and Drug Delivery)
  • Review
  • Open Access
44 Citations
7,605 Views
39 Pages

Adjuvant Drug-Assisted Bone Healing: Advances and Challenges in Drug Delivery Approaches

  • Rebecca Rothe,
  • Sandra Hauser,
  • Christin Neuber,
  • Markus Laube,
  • Sabine Schulze,
  • Stefan Rammelt and
  • Jens Pietzsch

Bone defects of critical size after compound fractures, infections, or tumor resections are a challenge in treatment. Particularly, this applies to bone defects in patients with impaired bone healing due to frequently occurring metabolic diseases (ab...

(This article belongs to the Special Issue Depot Delivery Systems: Recent Advances on Materials, Technologies, and Beyond)
  • Review
  • Open Access
381 Views
21 Pages

7 October 2026

The rat calvarial defect model supports the preclinical evaluation of bone-regenerative approaches relevant to craniofacial reconstruction, including recombinant human bone morphogenetic protein-2 (rhBMP-2) and bone substitutes. However, its invasive...

(This article belongs to the Section Veterinary Clinical Studies)
  • Review
  • Open Access
46 Citations
6,984 Views
20 Pages

Genetically Engineered-MSC Therapies for Non-unions, Delayed Unions and Critical-size Bone Defects

  • Jaime Freitas,
  • Susana Gomes Santos,
  • Raquel Madeira Gonçalves,
  • José Henrique Teixeira,
  • Mário Adolfo Barbosa and
  • Maria Inês Almeida

The normal bone regeneration process is a complex and coordinated series of events involving different cell types and molecules. However, this process is impaired in critical-size/large bone defects, with non-unions or delayed unions remaining a majo...

(This article belongs to the Special Issue Novel MSC Perspectives: From Cell Regulation to Tissue Regeneration)
  • Article
  • Open Access
7 Citations
3,231 Views
17 Pages

First Human Leucocyte Antigen (HLA) Response and Safety Evaluation of Fibrous Demineralized Bone Matrix in a Critical Size Femoral Defect Model of the Sprague-Dawley Rat

  • Nicolas Söhling,
  • Maximilian Leiblein,
  • Alexander Schaible,
  • Maren Janko,
  • Joachim Schwäble,
  • Christian Seidl,
  • Jan C. Brune,
  • Christoph Nau,
  • Ingo Marzi and
  • René D. Verboket
  • + 1 author

13 July 2020

Treatment of large bone defects is one of the great challenges in contemporary orthopedic and traumatic surgery. Grafts are necessary to support bone healing. A well-established allograft is demineralized bone matrix (DBM) prepared from donated human...

(This article belongs to the Section Biomaterials)
  • Article
  • Open Access
2 Citations
3,316 Views
19 Pages

Ex Vivo Regional Gene Therapy Compared to Recombinant BMP-2 for the Treatment of Critical-Size Bone Defects: An In Vivo Single-Cell RNA-Sequencing Study

  • Arijita Sarkar,
  • Matthew C. Gallo,
  • Jennifer A. Bell,
  • Cory K. Mayfield,
  • Jacob R. Ball,
  • Mina Ayad,
  • Elizabeth Lechtholz-Zey,
  • Stephanie W. Chang,
  • Osamu Sugiyama and
  • Jay R. Lieberman
  • + 1 author

Ex vivo regional gene therapy is a promising tissue-engineering strategy for bone regeneration: osteogenic mesenchymal stem cells (MSCs) can be genetically modified to express an osteoinductive stimulus (e.g., bone morphogenetic protein-2), seeded on...

(This article belongs to the Special Issue Advances in Bone Regeneration with Multipotential Stromal Cells and Bioactive Materials)
  • Article
  • Open Access
12 Citations
5,743 Views
15 Pages

Treatment of Critical Size Femoral Bone Defects with Biomimetic Hybrid Scaffolds of 3D Plotted Calcium Phosphate Cement and Mineralized Collagen Matrix

  • Anna Carla Culla,
  • Corina Vater,
  • Xinggui Tian,
  • Julia Bolte,
  • Tilman Ahlfeld,
  • Henriette Bretschneider,
  • Alexander Pape,
  • Stuart B. Goodman,
  • Michael Gelinsky and
  • Stefan Zwingenberger

To treat critical-size bone defects, composite materials and tissue-engineered bone grafts play important roles in bone repair materials. The purpose of this study was to investigate the bone regenerative potential of hybrid scaffolds consisting of m...

(This article belongs to the Special Issue Smart Biobased Polymers and Composites: Current Challenges and Opportunities)
  • Article
  • Open Access
36 Citations
5,019 Views
14 Pages

Evaluation of Mesenchymal Stem Cell Sheets Overexpressing BMP-7 in Canine Critical-Sized Bone Defects

  • Yongsun Kim,
  • Byung-Jae Kang,
  • Wan Hee Kim,
  • Hui-suk Yun and
  • Oh-kyeong Kweon

The aim of this study was to investigate the in vitro osteogenic capacity of bone morphogenetic protein 7 (BMP-7) overexpressing adipose-derived (Ad-) mesenchymal stem cells (MSCs) sheets (BMP-7-CS). In addition, BMP-7-CS were transplanted into criti...

(This article belongs to the Special Issue Biological Basis of Musculoskeletal Regeneration)

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