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Biomimetics
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Biomimetic Strategies to Enhance Bone Tissue Healing, Remodeling and Regeneration
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Biomimetic Strategies to Enhance Bone Tissue Healing, Remodeling and Regeneration

A special issue of Biomimetics (ISSN 2313-7673). This special issue belongs to the section "Biomimetics of Materials and Structures".

Deadline for manuscript submissions: closed (30 March 2025) | Viewed by 4041

Special Issue Editor

Dr. Otto Carl Wilson, Jr.

E-Mail Website
Guest Editor
Department of Biomedical Engineering, Catholic University of America, Washington, DC, USA
Interests: biomineralization phenomena; nanomaterials chemistry; biological liquid crystals; healing and remodeling of hard tissue

Special Issue Information

Dear Colleagues,

Bone tissue displays a number of unique chemical, physical, and biological characteristics which make it one of the most fascinating tissues in the body. Bone tissue plays an important physical role in providing structural support for our bodies and the foundation for tendon and ligament attachment for movement. Bone tissue also provides a physical environment for the protection of bone marrow tissue and internal organs. Bone tissue serves as a chemical storage depot for calcium and phosphate ions. These ions play a critically important role in a host of biological processes that are vital for life. These factors add to the importance of developing effective design strategies to maintain bone tissue health across the age spectrum from youth through to old age. One of the most important considerations in designing materials to enhance bone healing involves ensuring that the intervention is able to accompany the orchestra that resonates during bone tissue healing and remodeling without eliciting unfavorable effects.

Biomimetic design principles are based on learning from, modeling, and mimicking the processes that naturally occur during biological processes. Biomimetic design strategies and principles can be used to enhance the healing and remodeling of bone at the whole tissue, cellular, and subcellular levels and have shown much promise for future innovations in treatment. The focus of our Special Issue, entitled “Biomimetic Strategies to Enhance Bone Tissue Healing, Remodeling and Regeneration”, is to shine a spotlight on some of the key research studies that are being conducted in this field. These studies push the boundaries of our understanding of hard tissue healing phenomena and will pave the way for making great advances in optimizing skeletal health for life on Earth as well as the challenges of space travel as we venture beyond the earth.

Dr. Otto Carl Wilson, Jr.
Guest Editor

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. Biomimetics 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 2200 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

  • biomimetic strategies
  • bone repair
  • 3D scaffolds
  • bioceramics
  • bone grafts
  • orthopedic implants
  • bionic prostheses
  • bioresorbable material
  • biomechanics

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Published Papers (4 papers)

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Research

22 pages, 3030 KiB  
Article
Effect of Octacalcium Phosphate on Osteogenic Differentiation of Induced Pluripotent Stem Cells in a 3D Hybrid Spheroid Culture
by Yuki Sugai, Ryo Hamai, Yukari Shiwaku, Takahisa Anada, Kaori Tsuchiya, Tai Kimura, Manami Tadano, Kensuke Yamauchi, Tetsu Takahashi, Hiroshi Egusa and Osamu Suzuki
Biomimetics 2025, 10(4), 205; https://doi.org/10.3390/biomimetics10040205 - 26 Mar 2025
Viewed by 463
Abstract
Octacalcium phosphate (OCP) has been shown to exhibit an osteogenic property and, therefore, has been utilized recently as a bone substitute, clinically. However, the stimulatory capacity for induced pluripotent stem (iPS) cells is not known. This study investigated whether OCP enhances osteoblastic differentiation [...] Read more.
Octacalcium phosphate (OCP) has been shown to exhibit an osteogenic property and, therefore, has been utilized recently as a bone substitute, clinically. However, the stimulatory capacity for induced pluripotent stem (iPS) cells is not known. This study investigated whether OCP enhances osteoblastic differentiation of three-dimensionally cultured spheroids of iPS cells compared to hydroxyapatite (HA) and β-tricalcium phosphate (β-TCP). Mouse iPS cells were mixed with smaller (less than 53 μm) or larger (300–500 μm) sizes of calcium phosphate (CaP) granules and cultured in a laboratory-developed oxygen-permeable culture chip under minimizing hypoxia for up to 21 days. Osteoblastic differentiation was estimated by the cellular alkaline phosphatase (ALP) activities. The degree of supersaturation (DS) with respect to CaP phases was determined from the media chemical compositions. Incubated CaP materials were characterized by Fourier transform infrared spectroscopy (FTIR) and X-ray diffraction (XRD). The culture promoted well the formation of hybrid spheroids of CaP materials and iPS cells regardless of the type of materials and their granule sizes. The ALP activity of OCP was about 1.5 times higher than that of β-TCP and HA in smaller granule sizes. FTIR, XRD, and DS analyses showed that larger OCP granules tended to hydrolyze to HA slightly faster than smaller granules with time while HA and β-TCP materials tended to remain unchanged. In conclusion, the results suggest that OCP enhances the osteogenic differentiation of iPS cells more than HA and β-TCP through a mechanism of hydrolyzing to HA. This inherent material property of OCP is essential for enhancing the osteoblastic differentiation of iPS cells. Full article
(This article belongs to the Special Issue Biomimetic Strategies to Enhance Bone Tissue Healing, Remodeling and Regeneration)
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17 pages, 4901 KiB  
Article
Optimization of High-Frequency Ultrasound Imaging to Detect Incremental Changes in Mineral Content at the Cartilage–Bone Interface Ex Vivo
by Akshay Charan, Parag V. Chitnis and Caroline D. Hoemann
Biomimetics 2025, 10(3), 160; https://doi.org/10.3390/biomimetics10030160 - 5 Mar 2025
Viewed by 553
Abstract
(1) Background: Osteoarthritis is a degenerative disease of the whole joint marked by cartilage–bone interface (CBI) remodeling, but methods to monitor subtle changes in mineralization are lacking. We optimized a non-destructive ultrasound imaging method to monitor incremental shifts in mineralization, using brief decalcification [...] Read more.
(1) Background: Osteoarthritis is a degenerative disease of the whole joint marked by cartilage–bone interface (CBI) remodeling, but methods to monitor subtle changes in mineralization are lacking. We optimized a non-destructive ultrasound imaging method to monitor incremental shifts in mineralization, using brief decalcification as a mimetic of CBI remodeling. (2) Methods: We used a 35-MHz transducer to scan 3 mm diameter bovine osteochondral explants wrapped with parafilm to produce surface-directed decalcification and dedicated 3D-printed holders to maintain sample orientation. Customized MATLAB codes and a matched pair design were used for quantitative hypothesis testing. (3) Results: Optimal scan precision was obtained when the High-Frequency Ultrasound (HFUS) focal distance was trained at the CBI. HFUS cartilage thickness increased by 53 ± 21 µm or 97 ± 28 µm after three or seven hours of ethylene diamine tetra-acetic acid (EDTA) (but not PBS), respectively, and was highly correlated with histological cartilage thickness (R = 0.98). The en face CBI backscatter pattern was irregular and shifted after the EDTA-displacement of the mineral front. Collective data suggested that the −10 dB echogenic CBI signal originated from the mineral front and varied topographically with undulating mineral thickness. (4) Conclusions: This imaging approach could be used to monitor tidemark remodeling in live explant cultures, toward identifying new treatments that inhibit tidemark advancement and slow osteoarthritis progression. Full article
(This article belongs to the Special Issue Biomimetic Strategies to Enhance Bone Tissue Healing, Remodeling and Regeneration)
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16 pages, 4966 KiB  
Article
Polyetheretherketone Double Functionalization with Bioactive Peptides Improves Human Osteoblast Response
by Leonardo Cassari, Cristian Balducci, Grazia M. L. Messina, Giovanna Iucci, Chiara Battocchio, Federica Bertelà, Giovanni Lucchetta, Trevor Coward, Lucy Di Silvio, Giovanni Marletta, Annj Zamuner, Paola Brun and Monica Dettin
Biomimetics 2024, 9(12), 767; https://doi.org/10.3390/biomimetics9120767 - 17 Dec 2024
Cited by 1 | Viewed by 1013
Abstract
In recent years, the demand for orthopedic implants has surged due to increased life expectancy, necessitating the need for materials that better mimic the biomechanical properties of human bone. Traditional metal implants, despite their mechanical superiority and biocompatibility, often face challenges such as [...] Read more.
In recent years, the demand for orthopedic implants has surged due to increased life expectancy, necessitating the need for materials that better mimic the biomechanical properties of human bone. Traditional metal implants, despite their mechanical superiority and biocompatibility, often face challenges such as mismatched elastic modulus and ion release, leading to complications and implant failures. Polyetheretherketone (PEEK), a semi-crystalline polymer with an aromatic backbone, presents a promising alternative due to its adjustable elastic modulus and compatibility with bone tissue. This study explores the functionalization of sandblasted 3D-printed PEEK disks with the bioactive peptides Aoa-GBMP1α and Aoa-EAK to enhance human osteoblast response. Aoa-GBMP1α reproduces 48–69 trait of Bone Morphogenetic Protein 2 (BMP-2), whereas Aoa-EAK is a self-assembling peptide mimicking extracellular matrix (ECM) fibrous structure. Superficial characterization included X-ray photoelectron spectroscopy (XPS), white light interferometer analysis, static water contact angle (S-WCA), and force spectroscopy (AFM-FS). Biological assays demonstrated a significant increase in human osteoblast (HOB) proliferation, calcium deposition, and expression of osteogenic genes (RUNX2, SPP1, and VTN) on functionalized PEEK compared to non-functionalized controls. The findings suggest that dual peptide-functionalized PEEK holds significant potential for advancing orthopedic implant technology. Full article
(This article belongs to the Special Issue Biomimetic Strategies to Enhance Bone Tissue Healing, Remodeling and Regeneration)
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14 pages, 5633 KiB  
Article
A Murine Model of Non-Wear-Particle-Induced Aseptic Loosening
by Vincentius Suhardi, Anastasia Oktarina, Yingzhen Niu, Branden Sosa, Julia Retzky, Matthew Greenblatt, Lionel Ivashkiv, Mathias Bostrom and Xu Yang
Biomimetics 2024, 9(11), 673; https://doi.org/10.3390/biomimetics9110673 - 4 Nov 2024
Cited by 1 | Viewed by 1460
Abstract
Background: The current murine models of peri-implant osseointegration failure are associated with wear particles. However, the current clinical osseointegration failure is not associated with wear particles. Here, we develop a murine model of osseointegration failure not associated with wear particles and validate it [...] Read more.
Background: The current murine models of peri-implant osseointegration failure are associated with wear particles. However, the current clinical osseointegration failure is not associated with wear particles. Here, we develop a murine model of osseointegration failure not associated with wear particles and validate it by comparing the cellular composition of interfacial tissues with human samples collected during total joint arthroplasty revision for aseptic loosening. Materials and Methods: Thirty-two 16-week-old female C57BL/6 mice underwent implantation with a press-fitted roughened titanium implant (Control, n = 11) to induce normal osseointegration and a press-fitted smooth polymethylmethacrylate implant (PMMA, n = 11), a loosely fitted smooth titanium implant (Smooth-Ti, n = 5) or a loosely fitted roughened titanium implant (Overdrill, n = 5) to induce osseointegration failure. Pullout testing was used to determine the strength of the bone–implant interface (n = 6 of each for Control and PMMA groups) at 2 weeks after implantation. Histology (n = 2/group) and immunofluorescence (n = 3/group) were used to determine the cellular composition of bone–implant interfacial tissue, and this was compared with two human samples. Results: Osseointegration failure was confirmed with grossly loosening implants and the presence of fibrous tissue identified via histology. The maximum pullout load in the PMMA group was 87% lower than in the Control group (2.8 ± 0.6 N vs. 21 ± 1.5 N, p < 0.001). With immunofluorescence, abundant fibroblasts (PDGFRα+ TCF4+ and PDGFRα+ Pu1+) were observed in osseointegration failure groups and the human samples, but not in controls. Interestingly, CD146+PDGFRα+ and LepR+PDGFRα+ mesenchymal progenitors, osteoblasts (OPN+), vascular endothelium (EMCN+) cells were observed in all groups, indicating dynamic osteogenic activity. Macrophages, only M2, were observed in conditions producing fibrous tissue. Conclusions: In this newly developed non-wear-particle-related murine osseointegration failure model, the cellular composition of human and murine interfacial tissue implicates specific populations of fibroblasts in fibrous tissue formation and implies that these cells may derive from mesenchymal stem cells. Full article
(This article belongs to the Special Issue Biomimetic Strategies to Enhance Bone Tissue Healing, Remodeling and Regeneration)
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