Submit to Special Issue Submit Abstract to Special Issue Review for Biology Propose a Special Issue

Journal Menu

Journal Browser

► Journal Browser

Novel Insights of Bone Repair: Strategies for Improvement, Microscopic, Molecular and Ultrastrastructural Aspects

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Benefits of Publishing in a Special Issue
Published Papers

A special issue of Biology (ISSN 2079-7737).

Deadline for manuscript submissions: 31 July 2025 | Viewed by 13873

Share This Special Issue

Special Issue Editors

Dr. Roberta Okamoto

E-Mail Website
Guest Editor

Basic Sciences Department, São Paulo State University, Aracatuba 16018-805, Brazil
Interests: bone repair; pre-clinical models; systemic interferences and compromised bone; biomaterials

Dr. Kathryn Grandfield

Website
Guest Editor

Department of Materials Science and Engineering, McMaster University, Hamilton, ON, Canada
Interests: osseointegration; bone; biomineralization; electron microscopy; biointerfaces

Dr. Karina Carneiro

E-Mail Website
Guest Editor

1. Faculty of Dentistry, University of Toronto, Toronto, ON, Canada
2. Institute of Biomedical Engineering, University of Toronto, Toronto, ON, Canada
Interests: biomaterials; DNA nanotechnology; biomineralization; atomic force microscopy

Special Issue Information

Dear Colleagues,

Success in bone repair processes, by improving the quality of bone-restoring anatomy and function in the injury area, is a challenge. Aging and systemic interferences are situations that may impair the repair process or even the bone remodeling events that are part of calcium and phosphate homeostasis. Medication, in order to control systemic conditions, is the first action undertaken in order to improve bone repair quality. Recently, the participation of multidisciplinary fields has become an interesting strategy, especially considering the possibility of local action with biomaterials and different biomolecules in drug delivery systems may act in a synergistic way with the biological response of the repairing site.

The present Special Issue aims to explore the state of art in bone repair proceedings and the strategies used to improve the quality, maintaining the anatomy and physiology. The focus on new approaches that can lead to the improvement of cell responses and tissue events will encourage discussion on this topic. Different analyses of repair sites will be important in order to characterize bone in all of these special situations. Strategies focused on multidisciplinary approaches will play an important role in helping to achieve this goal.

In this Special Issue, original research articles and reviews are welcome. Research areas may include (but are not limited to) the following: articles focused on basic research, in vivo and ex in vivo models, as well as in vitro studies, biomaterials, drug delivery and other strategies that contribute to the improvement of repair processes. Articles with different analyses applied to characterize the repair process will also be acceptable.

Dr. Roberta Okamoto
Dr. Kathryn Grandfield
Dr. Karina Carneiro
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. Biology 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 repair
aging
bone remodeling
biomaterials
drug delivery
bone regeneration

Benefits of Publishing in a Special Issue

Ease of navigation: Grouping papers by topic helps scholars navigate broad scope journals more efficiently.
Greater discoverability: Special Issues support the reach and impact of scientific research. Articles in Special Issues are more discoverable and cited more frequently.
Expansion of research network: Special Issues facilitate connections among authors, fostering scientific collaborations.
External promotion: Articles in Special Issues are often promoted through the journal's social media, increasing their visibility.
Reprint: MDPI Books provides the opportunity to republish successful Special Issues in book format, both online and in print.

Further information on MDPI's Special Issue policies can be found here.

Published Papers (10 papers)

Download All Papers

Order results

Result details

Show export options Show export options

Select all

Export citation of selected articles as:

Research

Jump to: Other

13 pages, 9040 KiB

Open AccessArticle

Vitamin D3-Coated Surfaces and Their Role in Bone Repair and Peri-Implant Biomechanics

by Letícia Pitol-Palin, Isadora Castaldi Sousa, Juliani Caroline Ribeiro de Araújo, Fábio Roberto de Souza Batista, Bruna Kaori Namba Inoue, Paulo Roberto Botacin, Luana Marotta Reis de Vasconcellos, Paulo Noronha Lisboa-Filho and Roberta Okamoto

Biology 2025, 14(5), 476; https://doi.org/10.3390/biology14050476 - 26 Apr 2025

Viewed by 237

Abstract

Dental rehabilitation with titanium implants may requires the optimization of techniques and materials when oral conditions affect the successful treatment result. Thus, this study aims to customize the surface of titanium implants with bioactive vitamin D3 molecules to increase the performance of bone repair. The surfaces were functionalized following the “dip-coating” incorporation method with vitamin D3 in a solution of 1000 I.U./goat. The work was carried out in two stages: (I) physicochemical and biological tests (in vivo) in order to characterize and validate the vitamin D3 surface as well as its ability to affect peri-implant bone biomechanics; and (II) in vitro experiments to characterize viability responses, interaction and cell mineralization capacity. Scanning electron microscopy showed that the creation of vitamin D3 films is stable and homogeneous, while the in vivo results showed an increase in the biomechanical and microarchitectural capacity of the bone when vitamin D3 implants were used. Furthermore, the application of functionalized surfaces proved effective in promoting cell interaction and bone mineralization processes while preserving cell viability and capacity. In conclusion, the delivery of bioactive molecules based on vitamin D3 promotes changes in the surface microstructure of titanium, enabling an increase in the structural characteristics of bone tissue that result in an improvement in bone repair and peri-implant biomechanics. Full article

(This article belongs to the Special Issue Novel Insights of Bone Repair: Strategies for Improvement, Microscopic, Molecular and Ultrastrastructural Aspects)

► Show Figures

Figure 1

16 pages, 2971 KiB

Open AccessArticle

Rubus coreanus Enhances Peri-Implant Bone Healing and Biomineralization in Ovariectomized and Healthy Rats

by Naara Gabriela Monteiro, Odir Nunes de Oliveira-Filho, Maria Isabela Lopes Gandolfo, Ana Cláudia Ervolino da Silva, Letícia Pitol-Palin, Paulo Roberto Botacin, Gabriel Mulinari-Santos, Fábio Roberto de Souza Batista and Roberta Okamoto

Biology 2025, 14(2), 139; https://doi.org/10.3390/biology14020139 - 29 Jan 2025

Viewed by 845

Abstract

Estrogen deficiency contributes to osteoporosis and can therefore compromise the peri-implant bone. Hence, this study evaluated peri-implant bone healing when Rubus coreanus (RC) was administered orally in ovariectomized and healthy rats. Forty 4-month-old female rats were divided into four groups: SHAM (healthy rats), SHAM/RC (healthy rats treated with RC), OVX (ovariectomized rats), and OVX/RC (ovariectomized rats treated with RC). The oral administration of RC started thirty days after ovariectomy, and implant placement into the rat tibia occurred ninety days after the ovariectomy. Euthanasia occurred sixty days after implantation. The analyses performed included removal torque, RT-PCR, confocal microscopy, and immunolabeling. A significance level of p < 0.05 was considered for all tests. The highest reverse torque values were observed in the SHAM/RC group, followed by the OVX/RC group. Confocal microscopy showed the greatest bone biomineralization in the SHAM/RC group, followed by the OVX/RC group. RT-PCR data indicated that RC decreased the RANKL/OPG ratio in both conditions. Immunohistochemistry demonstrated a balance between bone formation and resorption in all groups, especially stimulating osteoblastogenesis in both treated groups. In conclusion, RC enhanced peri-implant bone healing and biomineralization in both healthy and ovariectomized rats, with stronger effects in healthy rats, suggesting that estrogen may enhance its efficacy. These findings support RC’s potential as a prophylactic and therapeutic agent. Full article

(This article belongs to the Special Issue Novel Insights of Bone Repair: Strategies for Improvement, Microscopic, Molecular and Ultrastrastructural Aspects)

► Show Figures

Figure 1

22 pages, 20383 KiB

Open AccessArticle

Inhibition of MEK1/2 Signaling Pathway Limits M2 Macrophage Polarization and Interferes in the Dental Socket Repair Process in Mice

by Angélica Cristina Fonseca, Priscila Maria Colavite, Michelle de Campos Soriani Azevedo, Daniela Carignatto Passadori, Jessica Lima Melchiades, Rafael Carneiro Ortiz, Camila Oliveira Rodini, Ana Paula Favaro Trombone and Gustavo Pompermaier Garlet

Biology 2025, 14(2), 107; https://doi.org/10.3390/biology14020107 - 21 Jan 2025

Viewed by 877

Abstract

Dental socket repair theoretically involves a constructive inflammatory immune response, which evolves from an initial M1 prevalence to a subsequent M2 dominance. In this scenario, the MEK1/2 signaling pathway is allegedly involved in M2 polarization. This study aimed to evaluate the impact of MEK1/2 pharmacological inhibition in the local host response and repair outcome. C57Bl/6-WT 8-week-old male mice were submitted to the extraction of the right upper incisor and treated (or not, control group) with MEK1/2 inhibitor PD0325901 (10 mg/kg/24 h/IP, MEK1/2i group) and analyzed at 0, 3, 7, and 14 days using microcomputed tomography, histomorphometry, birefringence, immunohistochemistry, and PCR array analysis. The results demonstrate that MEK1/2 inhibition limits the development of M2 response over time, being associated with lower expression of M2, MSCs, and bone markers, lower levels of growth and osteogenic factors, along with a higher expression of iNOS, IL-1b, IL-6, and TNF-α, as well inflammatory chemokines, indicating a predominantly M1 pro-inflammatory environment. This modulation of local inflammatory immune response is associated with impaired bone formation as demonstrated by microtomographic and histomorphometric data. The results show that MEK1/2 inhibition delays bone repair after tooth extraction, supporting the concept that M2 macrophages are essential elements for host response regulation and proper repair. Full article

(This article belongs to the Special Issue Novel Insights of Bone Repair: Strategies for Improvement, Microscopic, Molecular and Ultrastrastructural Aspects)

► Show Figures

Figure 1

22 pages, 6166 KiB

Open AccessArticle

Intermediate and Transitory Inflammation Mediate Proper Alveolar Bone Healing Outcome in Contrast to Extreme Low/High Responses: Evidence from Mice Strains Selected for Distinct Inflammatory Phenotypes

by Priscila Maria Colavite, Michelle de Campos Soriani Azevedo, Carolina Fávaro Francisconi, Angélica Cristina Fonseca, André Petenucci Tabanez, Jéssica Lima Melchiades, Daniela Carignatto Passadori, Andrea Borrego, Marcelo De Franco, Ana Paula Favaro Trombone and Gustavo Pompermaier Garlet

Biology 2024, 13(12), 972; https://doi.org/10.3390/biology13120972 - 25 Nov 2024

Viewed by 831

Abstract

Alveolar bone healing is influenced by various local and systemic factors, including the local inflammatory response. This study aimed to evaluate the role of inflammatory responsiveness in alveolar bone healing using 8-week-old male and female mice (N = 5/time/group) strains selected for maximum (AIRmax) or minimum (AIRmin) acute inflammatory response carrying distinct homozygous RR/SS Slc11a1 genotypes, namely AIRminRR, AIRminSS, AIRmaxRR, and AIRmaxSS mice. After upper right incisor extraction, bone healing was analyzed at 0, 3, 7, and 14 days using micro-computed tomography, histomorphometry, birefringence, immunohistochemistry, and PCRArray analysis. AIRmaxSS and AIRminRR presented the highest and lowest inflammatory readouts, respectively, associated with lowest repair levels in both strains, while intermediate inflammatory phenotypes observed in AIRminSS and AIRmaxRR were associated with higher repair levels in such strains. The better healing outcomes are associated with intermediate inflammatory cell counts, a balanced expression of pro- and anti-inflammatory cytokines and chemokines, increased expression of growth and osteogenic factors and MSCs markers. Our results demonstrate that extreme high and low inflammatory responses are not ideal for a proper bone repair outcome, while an intermediate and transitory inflammation is associated with a proper alveolar bone healing outcome. Full article

(This article belongs to the Special Issue Novel Insights of Bone Repair: Strategies for Improvement, Microscopic, Molecular and Ultrastrastructural Aspects)

► Show Figures

Figure 1

14 pages, 11700 KiB

Open AccessArticle

Does Ovariectomy Affect the Mechanics of the Mandibular Alveolar Bone Structure of Wistar Rats Subjected to Tooth Loss and Modified Diet?—A FEA Study

by Camila C. Furlan, Alexandre R. Freire, Beatriz C. Ferreira-Pileggi, Luciane N. O. Watanabe, Paulo R. Botacin, Felippe B. Prado and Ana Cláudia Rossi

Biology 2024, 13(11), 906; https://doi.org/10.3390/biology13110906 - 6 Nov 2024

Viewed by 1082

Abstract

The aim of this study was to evaluate the mechanical effect of ovariectomy, diet, and tooth extraction on the bone structure of the mandible of Wistar rats. Mandibles from 40 female Wistar rats were used, divided into rats with ovariectomy surgery or surgical simulation. Half of the rats had the right upper incisor extracted and a soft diet was introduced for half of the animals for 30 days. After euthanasia, microtomography of the mandibles was performed for bone segmentation to construct three-dimensional models. Each mandible was subjected to a three-point bending test. The simulation by finite element method was configured according to the protocol for positioning the part on the support and force action by the load cell defined in the mechanical tests. Stress dissipation was described qualitatively on a color scale distributed in ranges of stress values. All models showed a higher concentration of stresses in the regions of force action and in the support regions, with differences in stress values and locations. Diet and dental condition interfered in the distribution of stresses, with the lateral surface of the mandible being more influenced by diet and the medial surface of the mandible by diet and dental condition. Full article

(This article belongs to the Special Issue Novel Insights of Bone Repair: Strategies for Improvement, Microscopic, Molecular and Ultrastrastructural Aspects)

► Show Figures

Figure 1

17 pages, 8456 KiB

Open AccessArticle

Early Peri-Implant Bone Healing on Laser-Modified Surfaces with and without Hydroxyapatite Coating: An In Vivo Study

by Ana Flávia Piquera Santos, Rodrigo Capalbo da Silva, Henrique Hadad, Laís Kawamata de Jesus, Maísa Pereira-Silva, Heloisa Helena Nímia, Sandra Helena Penha Oliveira, Antônio Carlos Guastaldi, Thallita Pereira Queiroz, Pier Paolo Poli, Debora de Barros Barbosa, André Luis da Silva Fabris, Idelmo Rangel Garcia Júnior, Reinhard Gruber and Francisley Ávila Souza

Biology 2024, 13(7), 533; https://doi.org/10.3390/biology13070533 - 17 Jul 2024

Cited by 3 | Viewed by 2946 | Correction

Abstract

(1) Objective: The aim of this study was to assess the biological behavior of bone tissue on a machined surface (MS) and modifications made by a laser beam (LS) and by a laser beam incorporated with hydroxyapatite (HA) using a biomimetic method without thermic treatment (LHS). (2) Methods: Scanning electron microscopy coupled with energy-dispersive X-ray spectrometry (SEM/EDX) was performed before and after installation in the rabbit tibiae. A total of 20 Albinus rabbits randomly received 30 implants of 3.75 × 10 mm in the right and left tibias, with two implants on each surface in each tibia. In the animals belonging to the 4-week euthanasia period group, intramuscular application of the fluorochromes calcein and alizarin was performed. In implants placed mesially in the tibiofemoral joint, biomechanical analysis was performed by means of a removal torque (N/cm). The tibias with the implants located distally to the joint were submitted for analysis by confocal laser microscopy (mineral apposition rate) and for histometric analysis by bone contact implant (%BIC) and newly formed bone area (%NBA). (3) Results: The SEM showed differences between the surfaces. The biomechanical analysis revealed significant differences in removal torque values between the MSs and LHSs over a 2-week period. Over a 4-week period, both the LSs and LHSs demonstrated removal torque values statistically higher than the MSs. BIC of the LHS implants were statistically superior to MS at the 2-week period and LHS and LS surfaces were statistically superior to MS at the 4-week period. Statistical analysis of the NBA of the implants showed difference between the LHS and MS in the period of 2 weeks. (4) Conclusions: The modifications of the LSs and LHSs provided important physicochemical modifications that favored the deposition of bone tissue on the surface of the implants. Full article

(This article belongs to the Special Issue Novel Insights of Bone Repair: Strategies for Improvement, Microscopic, Molecular and Ultrastrastructural Aspects)

► Show Figures

Figure 1

12 pages, 4160 KiB

Open AccessArticle

Jaboticaba Peel Extract Attenuates Ovariectomy-Induced Bone Loss by Preserving Osteoblast Activity

by Letícia Faustino Adolpho, Maria Paula Oliveira Gomes, Gileade Pereira Freitas, Rayana Longo Bighetti-Trevisan, Jaqueline Isadora Reis Ramos, Gabriela Hernandes Campeoti, Guilherme Crepi Zatta, Adriana Luisa Gonçalves Almeida, Adriana Gadioli Tarone, Mario Roberto Marostica-Junior, Adalberto Luiz Rosa and Marcio Mateus Beloti

Biology 2024, 13(7), 526; https://doi.org/10.3390/biology13070526 - 16 Jul 2024

Cited by 1 | Viewed by 1301

Abstract

Therapies to prevent osteoporosis are relevant since it is one of the most common non-communicable human diseases in the world and the most prevalent bone disorder in adults. Since jaboticaba peel extract (JPE) added to the culture medium enhanced the osteogenic potential of mesenchymal stem cells (MSCs) derived from osteoporotic rats, we hypothesized that JPE prevents the development of ovariectomy-induced osteoporosis. Ovariectomized rats were treated with either JPE (30 mg/kg of body weight) or its vehicle for 90 days, starting 7 days after the ovariectomy. Then, the femurs were subjected to microcomputed tomography and histological analyses, and the osteoblast and adipocyte differentiation of MSCs was evaluated. JPE attenuated ovariectomy-induced bone loss, as evidenced by higher bone volume/total volume and trabecular number, along with lower trabecular separation and bone marrow adiposity. These protective effects of JPE on bone tissue are due to its ability to prevent the imbalance between osteoblast and adipocyte differentiation of MSCs, since, compared with MSCs derived from ovariectomized rats treated with vehicle, MSCs treated with JPE exhibited higher gene and protein expression of osteogenic markers and extracellular matrix mineralization, as well as lower gene expression of adipogenic markers. These data highlight the potential therapeutic use of JPE to prevent osteoporosis. Full article

(This article belongs to the Special Issue Novel Insights of Bone Repair: Strategies for Improvement, Microscopic, Molecular and Ultrastrastructural Aspects)

► Show Figures

Figure 1

15 pages, 3987 KiB

Open AccessArticle

Evaluation of Bone Repair Using a New Biphasic Synthetic Bioceramic (Plenum^® Oss_hp) in Critical Calvaria Defect in Rats

by Paula Buzo Frigério, Lilian Caldas Quirino, Marisa Aparecida Cabrini Gabrielli, Pedro Henrique de Azambuja Carvalho, Idelmo Rangel Garcia Júnior and Valfrido Antonio Pereira-Filho

Biology 2023, 12(11), 1417; https://doi.org/10.3390/biology12111417 - 10 Nov 2023

Cited by 5 | Viewed by 1588

Abstract

(1) Background: Biphasic bioceramics are synthetic bone substitutes that provide greater safety and better predictability in guided bone regeneration. This study aimed to evaluate the bone repair process using a new biphasic bioceramic of synthetic origin (Plenum^® Oss_hp—70HA: 30β-TCP) in critical calvarial defects. (2) Methods: seventy-four defects were created in rat calvaria and divided into two groups—Plenum^® Oss_hp (PO), right side, and Straumann^® BoneCeramic™ (BC), left side. Euthanasia was performed at 7, 15, 30, and 60 days after surgery. (3) Results: Lower gene expression was observed for runt-related transcription factor 2 (RUNX2) and vascular endothelial growth factor (VEGF) and higher expression for Integrin Binding Sialoprotein (IBSP). The results correlated with moderate immunolabeling for osteocalcin (OCN) and slight immunolabeling for osteopontin (OPN) in the PO group. Histometry showed a greater amount of biomaterial remaining in the PO group at 60 days. The microtomographic analysis showed a lower density of bone connectivity and a greater thickness of the trabeculae for the remnants of the PO group. (4) Conclusions: the Plenum^® Oss_hp showed no differences compared to BoneCeramic™ and is therefore considered an effective option as a synthetic bone substitute in bone regeneration. Full article

(This article belongs to the Special Issue Novel Insights of Bone Repair: Strategies for Improvement, Microscopic, Molecular and Ultrastrastructural Aspects)

► Show Figures

Figure 1

17 pages, 2327 KiB

Open AccessArticle

Effect of Mesenchymal Stem Cells Overexpressing BMP-9 Primed with Hypoxia on BMP Targets, Osteoblast Differentiation and Bone Repair

by Jessica Emanuella Rocha Moura Paz, Leticia Faustino Adolpho, Jaqueline Isadora Reis Ramos, Rayana Longo Bighetti-Trevisan, Robson Diego Calixto, Fabiola Singaretti Oliveira, Adriana Luisa Gonçalves Almeida, Marcio Mateus Beloti and Adalberto Luiz Rosa

Biology 2023, 12(8), 1147; https://doi.org/10.3390/biology12081147 - 19 Aug 2023

Cited by 1 | Viewed by 1888

Abstract

Bone formation is driven by many signaling molecules including bone morphogenetic protein 9 (BMP-9) and hypoxia-inducible factor 1-alpha (HIF-1α). We demonstrated that cell therapy using mesenchymal stem cells (MSCs) overexpressing BMP-9 (MSCs^+BMP-9) enhances bone formation in calvarial defects. Here, the effect of hypoxia on BMP components and targets of MSCs^+BMP-9 and of these hypoxia-primed cells on osteoblast differentiation and bone repair was evaluated. Hypoxia was induced with cobalt chloride (CoCl₂) in MSCs^+BMP-9, and the expression of BMP components and targets was evaluated. The paracrine effects of hypoxia-primed MSCs^+BMP-9 on cell viability and migration and osteoblast differentiation were evaluated using conditioned medium. The bone formation induced by hypoxia-primed MSCs^+BMP-9 directly injected into rat calvarial defects was also evaluated. The results demonstrated that hypoxia regulated BMP components and targets without affecting BMP-9 amount and that the conditioned medium generated under hypoxia favored cell migration and osteoblast differentiation. Hypoxia-primed MSCs^+BMP-9 did not increase bone repair compared with control MSCs^+BMP-9. Thus, despite the lack of effect of hypoxia on bone formation, the enhancement of cell migration and osteoblast differentiation opens windows for further investigations on approaches to modulate the BMP-9-HIF-1α circuit in the context of cell-based therapies to induce bone regeneration. Full article

(This article belongs to the Special Issue Novel Insights of Bone Repair: Strategies for Improvement, Microscopic, Molecular and Ultrastrastructural Aspects)

► Show Figures