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Functional Biomaterial for Bone Regeneration
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Functional Biomaterial for Bone Regeneration

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

Deadline for manuscript submissions: 31 May 2025 | Viewed by 5099

Special Issue Editors

Dr. Marija Čandrlić

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Guest Editor
Department of Integrative Dental Medicine, Faculty of Dental Medicine and Health Osijek, J.J. Strossmayer University of Osijek, Crkvena 21, 31 000 Osijek, Croatia
Interests: guided tissue regeneration; histology; immunohistochemistry; dental implantology; oral surgery
Dr. Željka Perić Kačarević

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Guest Editor
Department of Anatomy, Histology, Embryology, Pathological Anatomy and Pathological Histology, Faculty of Dental Medicine and Health, Josip Juraj Strossmayer University of Osijek, Crkvena 21, 31 000 Osijek, Croatia
Interests: biomaterials; histology; bone tissue regeneration; regenerative medicine; macrophages; collagen; resorbable metal
Special Issues, Collections and Topics in MDPI journals
Dr. Matej Tomas

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Guest Editor
Department of Dental Medicine, Faculty of Dental Medicine and Health Osijek, J.J. Strossmayer University of Osijek, Crkvena 21, 31 000 Osijek, Croatia
Interests: biomaterials; histology; bone tissue regeneration; immunohistochemistry; histomorphometry; periodontology
Special Issues, Collections and Topics in MDPI journals
Dr. Arun Kumar Rajendran

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Guest Editor
School of Chemical and Biological Engineering, Institute of Chemical Processes, Seoul National University, Seoul, Republic of Korea
Interests: bone regeneration; bioceramics; biopolymers; hydrogels; scaffolds; dentistry; angiogenesis; hemostasis; mechanosignalling; bone graft substitutes; bone fillers; bone cement; bioadhesives

Special Issue Information

Dear Colleagues,

It is generally recognized that the success of bone regeneration depends not only on the choice of a particular surgical technique and the clinical experience of the therapist, but also on the knowledge, correct selection, and use of various biomaterials. Therefore, the science of biomaterials is one of the fastest growing disciplines in dentistry, and a more thorough knowledge of the properties of existing biomaterials, as well as the development of new biomaterials, are certainly areas that require special research attention. We believe that the topic of this Special Issue is of great importance to professionals working in the field of tissue engineering, dental implantology, and regenerative dentistry, and that this issue provides a great opportunity to publish previously unaddressed topics related to biomaterials for bone regeneration.

Dr. Marija Čandrlić
Dr. Željka Perić Kačarević
Dr. Matej Tomas
Dr. Arun Kumar Rajendran
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

  • tissue regeneration
  • implant dentistry
  • bone substitutes
  • membranes
  • regenerative dental medicine

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Published Papers (5 papers)

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Research

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24 pages, 17467 KiB  
Article
Combined Effects of Dual-Scale Modified Surface with Micro- and Nanostructures on the Cellular Biocompatibility, Osteoinduction, and Antibacterial Properties of Titanium Implants
by Shaheer Maher, Nenad L. Ignjatović, Miloš Lazarević, Sanja Petrović, Andrijana Žekić and Dusan Losic
J. Funct. Biomater. 2025, 16(5), 157; https://doi.org/10.3390/jfb16050157 - 28 Apr 2025
Viewed by 61
Abstract
Titanium implants are widely used in biomedical applications due to their excellent mechanical properties and biocompatibility. However, implant-associated bacterial infections and suboptimal osseointegration remain significant challenges. Recent studies have demonstrated that the interplay between micro- and nanostructures can enhance both biocompatibility and antibacterial [...] Read more.
Titanium implants are widely used in biomedical applications due to their excellent mechanical properties and biocompatibility. However, implant-associated bacterial infections and suboptimal osseointegration remain significant challenges. Recent studies have demonstrated that the interplay between micro- and nanostructures can enhance both biocompatibility and antibacterial properties. This study explores the synergistic effects of hierarchical and dual surface topography on Ti surfaces with micro- and nanostructures to demonstrate their ability to promote cellular biocompatibility and osteoinduction while simultaneously inhibiting bacterial colonization. The combination of selective laser melting (SLM) to create micro-structured surfaces and hydrothermal processes is used to generate distinctive nanopillar structures. By integrating nanoscale features that mimic the extracellular matrix with microscale topographies that influence cellular responses, we achieve a balance between enhanced osseointegration and antimicrobial performance. The physicochemical properties of these dual-scale topographies are characterized through cellular assays using dental pulp stem cells (DPSCs), demonstrating sustained support for long-term cell viability (above 78% in MTT and NR assays (p < 0.05), low levels of LDH release, and high levels of cellular migration) and osteoinduction (statistically significant (p < 0.0001) ALP activity increase and higher levels of calcified matrix deposition, upregulation of ALP and OCN genes compared with smooth surface topographies). Their antibacterial properties against S. aureus and E. coli showed a significant reduction (p < 0.05) in bacterial attachment and biofilm formation. Our findings highlight the potential of multi-scale surface modifications as a promising strategy for next-generation titanium implants, paving the way for improved clinical outcomes in orthopedic and dental applications. Full article
(This article belongs to the Special Issue Functional Biomaterial for Bone Regeneration)
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16 pages, 2252 KiB  
Article
Impact of Vitamin D3 Functionalization on the Osteogenic Capacity of Bioinspired 3D Scaffolds Based on Ce-Doped Bioactive Glass and Spongia Agaricina
by Ana-Maria Seciu-Grama, Sorana Elena Lazăr, Simona Petrescu, Oana Cătălina Mocioiu, Oana Crăciunescu and Irina Atkinson
J. Funct. Biomater. 2025, 16(4), 141; https://doi.org/10.3390/jfb16040141 - 14 Apr 2025
Viewed by 371
Abstract
Reconstruction of extensive bone defects due to age, trauma, or post-illness conditions remains challenging. Biomimetic scaffolds with osteogenic capabilities have been proposed as an alternative to the classical autograft and allograft implants. Three-dimensional scaffolds were obtained based on Ce-doped mesoporous bioactive glass (MBG) [...] Read more.
Reconstruction of extensive bone defects due to age, trauma, or post-illness conditions remains challenging. Biomimetic scaffolds with osteogenic capabilities have been proposed as an alternative to the classical autograft and allograft implants. Three-dimensional scaffolds were obtained based on Ce-doped mesoporous bioactive glass (MBG) and Spongia agaricina (SA) as sacrificial templates functionalized with vitamin D3. The study aimed to investigate the effect of vitamin D3 functionalization on the optimal variant of a 3D scaffold doped with 3 mol% ceria, selected in our previous work based on its biological and physicochemical properties. Scanning electron microscopy (SEM) images of the non-functionalized/functionalized scaffolds revealed a porous structure with interconnected pores ranging from 100 to 350 μm. Fourier transform infrared spectroscopy (FTIR) and SEM analysis confirmed the surface functionalization. Cytotoxicity evaluation showed that all investigated scaffolds do not exhibit cytotoxicity and genotoxicity toward the Saos-2 osteosarcoma cell line. Moreover, the study demonstrated that functionalization with vitamin D3 enhanced osteogenic activity in dental pulp stem cells (DPSCs) by increasing calcium deposition and osteocalcin secretion, as determined by Alizarin red stain and a colorimetric ELISA kit, as a result of its synergistic action with cerium ions. The results showed that the Ce-doped MBG scaffold functionalized with vitamin D3 had the potential for applications in bone regeneration. Full article
(This article belongs to the Special Issue Functional Biomaterial for Bone Regeneration)
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16 pages, 8845 KiB  
Article
Cu-MOF-Decorated 3D-Printed Scaffolds for Infection Control and Bone Regeneration
by Ting Zhu, Qi Ni, Wenjie Wang, Dongdong Guo, Yixiao Li, Tianyu Chen, Dongyang Zhao, Xingyu Ma and Xiaojun Zhang
J. Funct. Biomater. 2025, 16(3), 83; https://doi.org/10.3390/jfb16030083 - 1 Mar 2025
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Abstract
Infection control and bone regeneration remain critical challenges in bone defect treatment. We developed a 3D-printed scaffold incorporating copper-based metal–organic framework-74 (Cu-MOF-74) within a polycaprolactone/hydroxyapatite composite. The synthesized Cu-MOF-74 exhibited a well-defined crystalline structure and rod-like morphology, as confirmed by TEM, EDS, FTIR, [...] Read more.
Infection control and bone regeneration remain critical challenges in bone defect treatment. We developed a 3D-printed scaffold incorporating copper-based metal–organic framework-74 (Cu-MOF-74) within a polycaprolactone/hydroxyapatite composite. The synthesized Cu-MOF-74 exhibited a well-defined crystalline structure and rod-like morphology, as confirmed by TEM, EDS, FTIR, and XRD analyses. The scaffolds exhibited hierarchical pores (100–200 μm) and demonstrated tunable hydrophilicity, as evidenced by the water contact angles decreasing from 103.3 ± 2.02° (0% Cu-MOF-74) to 63.60 ± 1.93° (1% Cu-MOF-74). A biphasic Cu2+ release profile was observed from the scaffolds, reaching cumulative concentrations of 98.97 ± 3.10 ppm by day 28. Antimicrobial assays showed concentration-dependent efficacy, with 1% Cu-MOF-74 scaffolds achieving 90.07 ± 1.94% and 80.03 ± 2.17% inhibition against Staphylococcus aureus and Escherichia coli, respectively. Biocompatibility assessments using bone marrow-derived mesenchymal stem cells revealed enhanced cell proliferation at Cu-MOF-74 concentrations ≤ 0.2%, while concentrations ≥ 0.5% induced cytotoxicity. Osteogenic differentiation studies highlighted elevated alkaline phosphatase activity and mineralization in scaffolds with 0.05–0.2% Cu-MOF-74 scaffolds, particularly at 0.05% Cu-MOF-74 scaffolds, which exhibited the highest calcium deposition and upregulation of bone sialoprotein and osteopontin expression. These findings demonstrate the dual functional efficacy of Cu-MOF-74/PCL/HAp scaffolds in promoting both infection control and bone regeneration. These optimized Cu-MOF-74 concentrations (0.05–0.2%) effectively balance antimicrobial and osteogenic properties, presenting a promising strategy for bone defect repair in clinical applications. Full article
(This article belongs to the Special Issue Functional Biomaterial for Bone Regeneration)
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16 pages, 13656 KiB  
Article
Regeneration of Critical Calvarial Bone Defects Using Bovine Xenograft, Magnesium-Enriched Bovine Xenograft and Autologous Dentin in Rats: Micro-CT, Gene Expression and Immunohistochemical Analysis
by Marija Čandrlić, Ana Terezija Jerbić Radetić, Hrvoje Omrčen, Barbara Franović, Lara Batičić, Tamara Gulić, Tea Čaljkušić-Mance, Sanja Zoričić Cvek, Lucija Malešić, Željka Perić Kačarević and Olga Cvijanović Peloza
J. Funct. Biomater. 2024, 15(9), 270; https://doi.org/10.3390/jfb15090270 - 18 Sep 2024
Viewed by 1821
Abstract
The aim of this study was to evaluate the efficacy of autologous dentin (AD), bovine xenograft (BX) and magnesium-enriched bovine xenograft (BX + Mg) in the healing of critical cranial bone defects (CCBDs) in rats. Eighty male Wistar rats were divided into four [...] Read more.
The aim of this study was to evaluate the efficacy of autologous dentin (AD), bovine xenograft (BX) and magnesium-enriched bovine xenograft (BX + Mg) in the healing of critical cranial bone defects (CCBDs) in rats. Eighty male Wistar rats were divided into four groups: BX, BX + Mg, AD and the control group (no intervention). Eight mm CCBDs were created and treated with the respective biomaterials. Healing was assessed 7, 15, 21 and 30 days after surgery by micro-computed tomography (micro-CT), real-time polymerase chain reaction (RT-PCR) and immunohistochemical analysis. Micro-CT analysis showed that AD had the highest bone volume and the least amount of residual biomaterial at day 30, indicating robust bone formation and efficient resorption. BX + Mg showed significant bone volume but had more residual biomaterial compared to AD. RT-PCR showed that the expression of osteocalcin (OC), the receptor activator of nuclear factor κB (RANK) and sclerostin (SOST), was highest in the AD group at day 21 and vascular endothelial growth factor (VEGF) at day 15, indicating increased osteogenesis and angiogenesis in the AD group. Immunohistochemical staining confirmed intense BMP-2/4 and SMAD-1/5/8 expression in the AD group, indicating osteoinductive properties. The favorable gene expression profile and biocompatibility of AD and BX + Mg make them promising candidates for clinical applications in bone tissue engineering. Further research is required to fully exploit their potential in regenerative surgery. Full article
(This article belongs to the Special Issue Functional Biomaterial for Bone Regeneration)
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21 pages, 959 KiB  
Systematic Review
Evaluating Bioassays for the Determination of Simvastatin’s Osteogenic Activity: A Systematic Review
by Lara Steiner Back, Isabella Schönhofen Manso, Mariane Beatriz Sordi, Gabriel Leonardo Magrin, Águedo Aragonês, Ricardo de Souza Magini, Reinhard Gruber and Ariadne Cristiane Cabral Cruz
J. Funct. Biomater. 2025, 16(2), 61; https://doi.org/10.3390/jfb16020061 - 11 Feb 2025
Viewed by 695
Abstract
Objective: Osteogenic differentiation is a complex process, and its analysis requires several biomarkers. Allied with this, there are no standardized bioassays to monitor the activity of simvastatin in osteogenesis in vitro. Therefore, identifying the most efficient and sensitive bioassays may enhance the quality [...] Read more.
Objective: Osteogenic differentiation is a complex process, and its analysis requires several biomarkers. Allied with this, there are no standardized bioassays to monitor the activity of simvastatin in osteogenesis in vitro. Therefore, identifying the most efficient and sensitive bioassays may enhance the quality of in vitro studies, bridging the gap with in vivo findings, saving time and resources, and benefiting the community. This systematic review aimed to determine the most efficient bioassay for simvastatin’s osteogenic activity in vitro, in terms of sensitivity. Materials and Methods: In vitro studies evaluating undifferentiated mesenchymal cells treated with simvastatin were considered eligible. References were selected in a two-phase process. Electronic databases and the grey literature were screened up to September 2023. The Office of Health Assessment and Translation (OHAT) tool was used to assess the risk of bias. Certainty in cumulative evidence was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) criteria. Data were analyzed considering extracellular matrix mineralization, alkaline phosphatase, and the expression of potential target genes, such as bone morphogenetic protein-2 (BMP-2), collagen type I, Runt-related transcription factor 2, osterix, osteocalcin, and osteopontin. Results: Fourteen studies were included. A “probably low” or a “definitely low” risk of bias was assigned to the included studies. The simvastatin concentration ranged from 0.1 nM to 10 µM. Considering a minimum 4-fold increase, simvastatin caused robust mineralization of the extracellular matrix in four studies (4.0-, 4.4-, 5.0-, and 39.5-fold). Moreover, simvastatin substantially increased BMP-2 expression in mesenchymal cells in three studies (4-, 11-, and 19-fold). Conclusion: Therefore, mineralization of the extracellular matrix and BMP-2 expression in mesenchymal cells are the most efficient bioassays for determining the osteogenic activity of simvastatin in vitro (high certainty level). These findings provide a standardized approach that can enhance the reliability and comparability of in vitro studies, bridging the gap with in vivo research and optimizing resources in the field of bone regeneration. Full article
(This article belongs to the Special Issue Functional Biomaterial for Bone Regeneration)
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