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

Deadline for manuscript submissions: closed (20 July 2024) | Viewed by 31799

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Special Issue Editors

Prof. Dr. Feng Chen

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Guest Editor

1. Center for Orthopedic Science and Transnational Medicine, Shanghai Tenth People's Hospital, Shanghai, China
2. School of Medicine, Tongji University, Shanghai, China
Interests: bio-inspired materials; biomineralization; bone regeneration; bioprinting; tissue engineering; dental materials; osteosarcoma

Dr. Zifei Zhou

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Guest Editor

1. Center for Orthopedic Science and Transnational Medicine, Shanghai Tenth People's Hospital, Shanghai, China
2. School of Medicine, Tongji University, Shanghai, China
Interests: biomimetic materials; tissue engineering; biomineralization; bone regeneration; bone tumor

Special Issue Information

Dear Colleagues,

Bone is a typical mineralized tissue, which plays a critical role in protecting and maintaining the shape of the human body. Meanwhile, bone is also a place where inorganic ions are stored and various blood cells are produced. The treatment of bone diseases is one of the most important issues in the clinical work of orthopedics, in which the use of biomaterials is becoming increasingly important. In terms of chemical composition, the types of bone biomaterials include metals, inorganic non-metals, natural polymers, synthetic polymers, and cell-derived materials, which are used in the form of porous scaffolds, membranes, hydrogels, nanomaterials, etc. In recent decades, the development of bone biomaterials has rapidly promoted the clinical treatment strategies of orthopedic diseases.

This Special Issue will host papers (communications, articles, and reviews) related to the latest findings and trends in the field of bone biomaterials. Topics may include, but are not limited to, the following: bone implants, metal/ceramic biomaterials, surface modification, biomimetic materials, biomineralization, bone/cartilage regeneration, 3D/4D printed scaffolds, biosafety/bioactivity evaluation, and bone tumor-related nanomedicine.

Prof. Dr. Feng Chen
Dr. Zifei Zhou
Guest Editors

Manuscript Submission Information

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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.

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Keywords

bone implant
biomimetic materials
biomineralization
calcium phosphate
surface modification
tissue regeneration
biosafety
bioactivity
osteosarcoma
nanomedicine

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Published Papers (10 papers)

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Research

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17 pages, 3824 KiB

Open AccessArticle

Chemically Pretreated Densification of Juniper Wood for Potential Use in Osteosynthesis Bone Implants

by Laura Andze, Vadims Nefjodovs, Martins Andzs, Marite Skute, Juris Zoldners, Martins Kapickis, Arita Dubnika, Janis Locs and Janis Vetra

J. Funct. Biomater. 2024, 15(10), 287; https://doi.org/10.3390/jfb15100287 - 28 Sep 2024

Viewed by 635

Abstract

The aim of the study was to perform treatment of juniper wood to obtain wood material with a density and mechanical properties comparable to bone, thus producing a potential material for use in osteosynthesis bone implants. In the first step, partial delignification of wood sample was obtained by Kraft cooking. The second step was extraction with ethanol, ethanol–water mixture, saline, and water to prevent the release of soluble compounds and increase biocompatibility. In the last step, the thermal densification at 100 °C for 24 h was implemented. The results obtained in the dry state are equivalent to the properties of bone. The swelling of chemically pre-treated densified wood was reduced compared to chemically untreated densified wood. Samples showed no cytotoxicity by in vitro cell assays. The results of the study showed that it is possible to obtain noncytotoxic wood samples with mechanical properties equivalent to bones by partial delignification, extraction, and densification. However, further research is needed to ensure the material’s shape stability, water resistance, and reduced swelling. Full article

(This article belongs to the Special Issue Feature Papers in Bone Biomaterials)

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20 pages, 8416 KiB

Open AccessEditor’s ChoiceArticle

In Vitro Biocompatibility Assessment of Bioengineered PLA-Hydrogel Core–Shell Scaffolds with Mesenchymal Stromal Cells for Bone Regeneration

by Federica Re, Luciana Sartore, Chiara Pasini, Matteo Ferroni, Elisa Borsani, Stefano Pandini, Andrea Bianchetti, Camillo Almici, Lorena Giugno, Roberto Bresciani, Silvia Mutti, Federica Trenta, Simona Bernardi, Mirko Farina and Domenico Russo

J. Funct. Biomater. 2024, 15(8), 217; https://doi.org/10.3390/jfb15080217 - 31 Jul 2024

Viewed by 3176

Abstract

Human mesenchymal stromal cells (hMSCs), whether used alone or together with three-dimensional scaffolds, are the best-studied postnatal stem cells in regenerative medicine. In this study, innovative composite scaffolds consisting of a core–shell architecture were seeded with bone-marrow-derived hMSCs (BM-hMSCs) and tested for their biocompatibility and remarkable capacity to promote and support bone regeneration and mineralization. The scaffolds were prepared by grafting three different amounts of gelatin–chitosan (CH) hydrogel into a 3D-printed polylactic acid (PLA) core (PLA-CH), and the mechanical and degradation properties were analyzed. The BM-hMSCs were cultured in the scaffolds with the presence of growth medium (GM) or osteogenic medium (OM) with differentiation stimuli in combination with fetal bovine serum (FBS) or human platelet lysate (hPL). The primary objective was to determine the viability, proliferation, morphology, and spreading capacity of BM-hMSCs within the scaffolds, thereby confirming their biocompatibility. Secondly, the BM-hMSCs were shown to differentiate into osteoblasts and to facilitate scaffold mineralization. This was evinced by a positive Von Kossa result, the modulation of differentiation markers (osteocalcin and osteopontin), an expression of a marker of extracellular matrix remodeling (bone morphogenetic protein-2), and collagen I. The results of the energy-dispersive X-ray analysis (EDS) clearly demonstrate the presence of calcium and phosphorus in the samples that were incubated in OM, in the presence of FBS and hPL, but not in GM. The chemical distribution maps of calcium and phosphorus indicate that these elements are co-localized in the same areas of the sections, demonstrating the formation of hydroxyapatite. In conclusion, our findings show that the combination of BM-hMSCs and PLA-CH, regardless of the amount of hydrogel content, in the presence of differentiation stimuli, can provide a construct with enhanced osteogenicity for clinically relevant bone regeneration. Full article

(This article belongs to the Special Issue Feature Papers in Bone Biomaterials)

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13 pages, 4856 KiB

Open AccessArticle

Analysis of Bone Mineral Density and Bone Quality of Cortical Bone in the Human Hyoid Body and Histological Observation of the Entheses

by Masaaki Kasahara, Tomoko Someya, Kei Kitamura, Genji Watanabe, Satoru Matsunaga, Shinichi Abe and Masayuki Hattori

J. Funct. Biomater. 2024, 15(3), 56; https://doi.org/10.3390/jfb15030056 - 22 Feb 2024

Cited by 1 | Viewed by 1711

Abstract

The hyoid is the only bone in the human body that is completely independent, not forming a joint with any other bone; its position is maintained by the suprahyoid and infrahyoid muscles, as well as several ligaments. The purpose of this study was to ascertain the effect of the functional pressure arising from these muscles and ligaments on the hyoid body structure from its bone mineral density, bone quality, and histological observations. The area between the mesial-most part of each lesser horn and the center of the hyoid body was divided equally into four measurement regions. We conducted histological investigations at each measurement region and observed the entheses. To analyze bone mass and bone quality, we also measured bone mineral density (BMD) and analyzed biological apatite (BAp) crystallite orientation in the same regions. Histological observations identified periosteal insertions and fibrocartilaginous entheses. There was no significant difference in BMD between any of the measurement regions, but the preferential orientation of BAp crystallites was stronger in the infrahyoid muscles and ligaments, where fibrocartilaginous entheses are found, than in other places. This suggests that the functional pressure at these sites might exert a major effect not only on the morphological characteristics of the entheses but also on bone quality. Full article

(This article belongs to the Special Issue Feature Papers in Bone Biomaterials)

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13 pages, 3031 KiB

Open AccessArticle

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

by 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, Mônica D. Calasans-Maia, José Mauro Granjeiro and Leandra Santos Baptista

J. Funct. Biomater. 2023, 14(12), 555; https://doi.org/10.3390/jfb14120555 - 21 Nov 2023

Cited by 1 | Viewed by 2166

Abstract

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 capacity of ASC spheroids in bone regeneration using a synergic strategy with 3D-printed scaffolds made from poly (lactic acid) (PLA) and nanostructured hydroxyapatite doped with carbonate ions (CHA) in a rat model of cranial critical-size defect. In summary, a set of results suggests that ASC spheroidal constructs promoted bone regeneration. In vitro results showed that ASC spheroids were able to spread and interact with the 3D-printed scaffold, synthesizing crucial growth factors and cytokines for bone regeneration, such as VEGF. Histological results after 3 and 6 months of implantation showed the formation of new bone tissue in the PLA/CHA scaffolds that were seeded with ASC spheroids. In conclusion, the presence of ASC spheroids in the PLA/CHA 3D-printed scaffolds seems to successfully promote bone formation, which can be crucial for a significant clinical improvement in critical bone defect regeneration. Full article

(This article belongs to the Special Issue Feature Papers in Bone Biomaterials)

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18 pages, 7902 KiB

Open AccessEditor’s ChoiceArticle

Manganese-Implanted Titanium Modulates the Crosstalk between Bone Marrow Mesenchymal Stem Cells and Macrophages to Improve Osteogenesis

by Kuicai Ye, Xianming Zhang, Li Shangguan, Xingdan Liu, Xiaoshuang Nie and Yuqin Qiao

J. Funct. Biomater. 2023, 14(9), 456; https://doi.org/10.3390/jfb14090456 - 3 Sep 2023

Cited by 3 | Viewed by 2044

Abstract

Manganese (Mn) is an essential micronutrient in various physiological processes, but its functions in bone metabolism remain undefined. This is partly due to the interplay between immune and bone cells because Mn plays a central role in the immune system. In this study, we utilized the plasma immersion ion implantation and deposition (PIII&D) technique to introduce Mn onto the titanium surface. The results demonstrated that Mn-implanted surfaces stimulated the shift of macrophages toward the M1 phenotype and had minimal effects on the osteogenic differentiation of mouse bone marrow mesenchymal stem cells (mBMSCs) under mono-culture conditions. However, they promoted the M2 polarization of macrophages and improved the osteogenic activities of mBMSCs under co-culture conditions, indicating the importance of the crosstalk between mBMSCs and macrophages mediated by Mn in osteogenic activities. This study provides a positive incentive for the application of Mn in the field of osteoimmunology. Full article

(This article belongs to the Special Issue Feature Papers in Bone Biomaterials)

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13 pages, 12948 KiB

Open AccessArticle

Photobiomodulation and Inorganic Bovine Bone in Guided Bone Regeneration: Histomorphometric Analysis in Rats

by Nicole Rosa de Freitas, Luísa Belluco Guerrini, Luis Augusto Esper, Michyele Cristhiane Sbrana, Caroline Chepernate Vieira dos Santos and Ana Lúcia Pompéia Fraga de Almeida

J. Funct. Biomater. 2023, 14(5), 281; https://doi.org/10.3390/jfb14050281 - 18 May 2023

Cited by 4 | Viewed by 1625

Abstract

The objective of this study was to evaluate the efficacy of photobiomodulation in the bone regeneration of critical-sized defects (CSD) filled with inorganic bovine bone associated or not with collagen membranes. The study has been conducted on 40 critical defects in the calvaria of male rats, divided into four experimental groups (n = 10): (1) DBBM (deproteinized bovine bone mineral); (2) GBR (DBBM+collagen membrane); (3) DBBM+P (DBBM+photobiomodulation); and (4) GBR+P (GBR+photobiomodulation). At 30 days postoperative, the animals were euthanized, and after the tissue had been processed, histological, histometric, and statistical analyses were performed. The analyses have taken into account newly formed bone area (NBA), linear bone extension (LBE), and residual particle area (RPA) as variables. The Kruskal-Wallis test has been performed, followed by the Dwass-Steel-Critchlow-Fligner test for comparison between groups (p < 0.05). When the DBBM+P group was compared to the DBBM group, it was possible to observe significant statistical differences in all the variables analyzed (p < 0.05). The application of photobiomodulation in guided bone regeneration (GBR+P) has shown a decrease in the median value for the RPA variable (26.8) when compared to the GBR group (32.4), with a significant statistical difference; however, for NBA and LBE, the therapy has not provided significant results. Full article

(This article belongs to the Special Issue Feature Papers in Bone Biomaterials)

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17 pages, 3896 KiB

Open AccessEditor’s ChoiceArticle

Biodegradable Mg-Sc-Sr Alloy Improves Osteogenesis and Angiogenesis to Accelerate Bone Defect Restoration

by Nadia Aboutalebianaraki, Craig J. Neal, Sudipta Seal and Mehdi Razavi

J. Funct. Biomater. 2022, 13(4), 261; https://doi.org/10.3390/jfb13040261 - 22 Nov 2022

Cited by 9 | Viewed by 2318

Abstract

Magnesium (Mg) and its alloys are considered to be biodegradable metallic biomaterials for potential orthopedic implants. While the osteogenic properties of Mg alloys have been widely studied, few reports focused on developing a bifunctional Mg implant with osteogenic and angiogenic properties. Herein, a Mg-Sc-Sr alloy was developed, and this alloy’s angiogenesis and osteogenesis effects were evaluated in vitro for the first time. X-ray Fluorescence (XRF), X-ray diffraction (XRD), and metallography images were used to evaluate the microstructure of the developed Mg-Sc-Sr alloy. Human umbilical vein/vascular endothelial cells (HUVECs) were used to evaluate the angiogenic character of the prepared Mg-Sc-Sr alloy. A mix of human bone-marrow-derived mesenchymal stromal cells (hBM-MSCs) and HUVEC cell cultures were used to assess the osteogenesis-stimulating effect of Mg-Sc-Sr alloy through alkaline phosphatase (ALP) and Von Kossa staining. Higher ALP activity and the number of calcified nodules (27% increase) were obtained for the Mg-Sc-Sr-treated groups compared to Mg-treated groups. In addition, higher VEGF expression (45.5% increase), tube length (80.8% increase), and number of meshes (37.9% increase) were observed. The Mg-Sc-Sr alloy showed significantly higher angiogenesis and osteogenic differentiation than pure Mg and the control group, suggesting such a composition as a promising candidate in bone implants. Full article

(This article belongs to the Special Issue Feature Papers in Bone Biomaterials)

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14 pages, 21377 KiB

Open AccessEditor’s ChoiceArticle

Engineering Nanopatterned Structures to Orchestrate Macrophage Phenotype by Cell Shape

by Kai Li, Lin Lv, Dandan Shao, Youtao Xie, Yunzhen Cao and Xuebin Zheng

J. Funct. Biomater. 2022, 13(1), 31; https://doi.org/10.3390/jfb13010031 - 14 Mar 2022

Cited by 15 | Viewed by 3645

Abstract

Physical features on the biomaterial surface are known to affect macrophage cell shape and phenotype, providing opportunities for the design of novel “immune-instructive” topographies to modulate foreign body response. The work presented here employed nanopatterned polydimethylsiloxane substrates with well-characterized nanopillars and nanopits to assess RAW264.7 macrophage response to feature size. Macrophages responded to the small nanopillars (SNPLs) substrates (450 nm in diameter with average 300 nm edge-edge spacing), resulting in larger and well-spread cell morphology. Increasing interpillar distance to 800 nm in the large nanopillars (LNPLs) led to macrophages exhibiting morphologies similar to being cultured on the flat control. Macrophages responded to the nanopits (NPTs with 150 nm deep and average 800 nm edge-edge spacing) by a significant increase in cell elongation. Elongation and well-spread cell shape led to expression of anti-inflammatory/pro-healing (M2) phenotypic markers and downregulated expression of inflammatory cytokines. SNPLs and NPTs with high availability of integrin binding region of fibronectin facilitated integrin β1 expression and thus stored focal adhesion formation. Increased integrin β1 expression in macrophages on the SNPLs and NTPs was required for activation of the PI3K/Akt pathway, which promoted macrophage cell spreading and negatively regulated NF-κB activation as evidenced by similar globular cell shape and higher level of NF-κB expression after PI3K blockade. These observations suggested that alterations in macrophage cell shape from surface nanotopographies may provide vital cues to orchestrate macrophage phenotype. Full article

(This article belongs to the Special Issue Feature Papers in Bone Biomaterials)

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Review

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26 pages, 13094 KiB

Open AccessReview

Musculoskeletal Biomaterials: Stimulated and Synergized with Low Intensity Pulsed Ultrasound

by Wanru Jia, Zifei Zhou and Weiwei Zhan

J. Funct. Biomater. 2023, 14(10), 504; https://doi.org/10.3390/jfb14100504 - 9 Oct 2023

Cited by 2 | Viewed by 2299

Abstract

Clinical biophysical stimulating strategies, which have significant effects on improving the function of organs or treating diseases by causing the salutary response of body, have shown many advantages, such as non-invasiveness, few side effects, and controllable treatment process. As a critical technique for stimulation, the low intensity pulsed ultrasound (LIPUS) has been explored in regulating osteogenesis, which has presented great promise in bone repair by delivering a combined effect with biomaterials. This review summarizes the musculoskeletal biomaterials that can be synergized with LIPUS for enhanced biomedical application, including bone regeneration, spinal fusion, osteonecrosis/osteolysis, cartilage repair, and nerve regeneration. Different types of biomaterials are categorized for summary and evaluation. In each subtype, the verified biological mechanisms are listed in a table or graphs to prove how LIPUS was effective in improving musculoskeletal tissue regeneration. Meanwhile, the acoustic excitation parameters of LIPUS that were promising to be effective for further musculoskeletal tissue engineering are discussed, as well as their limitations and some perspectives for future research. Overall, coupled with biomimetic scaffolds and platforms, LIPUS may be a powerful therapeutic approach to accelerate musculoskeletal tissue repair and even in other regenerative medicine applications. Full article

(This article belongs to the Special Issue Feature Papers in Bone Biomaterials)

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39 pages, 11595 KiB

Open AccessEditor’s ChoiceReview

Calcium Phosphate-Based Biomaterials for Bone Repair

by Xiaodong Hou, Lei Zhang, Zifei Zhou, Xiong Luo, Tianlong Wang, Xinyu Zhao, Bingqiang Lu, Feng Chen and Longpo Zheng

J. Funct. Biomater. 2022, 13(4), 187; https://doi.org/10.3390/jfb13040187 - 14 Oct 2022

Cited by 108 | Viewed by 10810

Abstract

Traumatic, tumoral, and infectious bone defects are common in clinics, and create a big burden on patient’s families and society. Calcium phosphate (CaP)-based biomaterials have superior properties and have been widely used for bone defect repair, due to their similarities to the inorganic components of human bones. The biological performance of CaPs, as a determining factor for their applications, are dependent on their physicochemical properties. Hydroxyapatite (HAP) as the most thermally stable crystalline phase of CaP is mostly used in the form of ceramics or composites scaffolds with polymers. Nanostructured CaPs with large surface areas are suitable for drug/gene delivery systems. Additionally, CaP scaffolds with hierarchical nano-/microstructures have demonstrated excellent ability in promoting bone regeneration. This review focuses on the relationships and interactions between the physicochemical/biological properties of CaP biomaterials and their species, sizes, and morphologies in bone regeneration, including synthesis strategies, structure control, biological behavior, and the mechanisms of CaP in promoting osteogenesis. This review will be helpful for scientists and engineers to further understand CaP-based biomaterials (CaPs), and be useful in developing new high-performance biomaterials for bone repair. Full article

(This article belongs to the Special Issue Feature Papers in Bone Biomaterials)

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