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Biological Cues for Tissue Regeneration and Bioactive Materials

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: closed (15 December 2022) | Viewed by 13905

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Dr. Thaqif El Khassawna

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Guest Editor

Experimentelle Unfallchirurgie, FB11 Medizinisches Forschungszentrum (ForMed) Aulweg 128, D-35392 Gießen, Germany
Interests: tissue regeneration; bioactive materials; cell delivery systems; nanostructured materials

Special Issue Information

Dear Colleagues,

Regenerative medicine aims at restoring lost soft or hard tissues with functional ones. The challenge increases exponentially when the engineered tissue has to replace a large defect, be used in aseptic conditions, or to overcome a systemic disease. Nonetheless, understanding the biological cues of soft and hard tissue healing is crucial to design functionalized biomaterials which target the affected cue and ensure a functional healing in the mechanical and physiological sense. To achieve such functionality, tissue engineering and material science tools depend on: 1) creating similar structures to the lost tissue through a better three-dimensional design, 2) reflect the biological understanding of the tissue to deliver specific agents that would either enhance or reduce specific cellular activities or infections, 3) use cell therapy approaches to achieve functional healing, and finally 5) use combinations of some or even all options. The achievement brought by the innovation of biomaterials enhanced their biocompatibility, biodegradability, and structural similarity to the target tissue (bioinspired materials) to promote healing especially in challenged situations.

Delivery of nano and micro bioactive molecules has many methods as the supporting matrix directly, or binding to the material surface, or covalently linking cell adhesion molecules to the scaffold. Furthermore, nanotechnology enabled the structuring of novel biomaterials with customized mechanical and physiological properties to stimulate regeneration of soft and hard tissues.

The scope of this special issue aims to cover the understanding of biological cues in tissue regeneration, the fabrication of nanostructured biomaterials and bioactive materials potential to achieve recovery of tissue function.

Dr. Thaqif El Khassawna
Guest Editor

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Keywords

tissue regeneration
bioactive materials
cell delivery systems
nanostructured materials
in vitro models

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Published Papers (5 papers)

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Research

28 pages, 3946 KiB

Open AccessArticle

Landscape of Well-Coordinated Fracture Healing in a Mouse Model Using Molecular and Cellular Analysis

by Deeksha Malhan, Katharina Schmidt-Bleek, Georg N. Duda and Thaqif El Khassawna

Int. J. Mol. Sci. 2023, 24(4), 3569; https://doi.org/10.3390/ijms24043569 - 10 Feb 2023

Cited by 3 | Viewed by 2494

Abstract

The success of fracture healing relies on overlapping but coordinated cellular and molecular events. Characterizing an outline of differential gene regulation throughout successful healing is essential for identifying crucial phase-specific markers and may serve as the basis for engineering these in challenging healing situations. This study analyzed the healing progression of a standard closed femoral fracture model in C57BL/6N (age = 8 weeks) wild-type male mice. The fracture callus was assessed across various days post fracture (D = days 0, 3, 7, 10, 14, 21, and 28) by microarray, with D0 serving as a control. Histological analyses were carried out on samples from D7 until D28 to support the molecular findings. Microarray analysis revealed a differential regulation of immune response, angiogenesis, ossification, extracellular matrix regulation, mitochondrial and ribosomal genes during healing. In-depth analysis showed differential regulation of mitochondrial and ribosomal genes during the initial phase of healing. Furthermore, the differential gene expression showed an essential role of Serpin Family F Member 1 over the well-known Vascular Endothelial Growth Factor in angiogenesis, especially during the inflammatory phase. The significant upregulation of matrix metalloproteinase 13 and bone sialoprotein from D3 until D21 asserts their importance in bone mineralization. The study also shows type I collagen around osteocytes located in the ossified region at the periosteal surface during the first week of healing. Histological analysis of matrix extracellular phosphoglycoprotein and extracellular signal-regulated kinase stressed their roles in bone homeostasis and the physiological bone-healing process. This study reveals previously unknown and novel candidates, that could serve as a target for specific time points in healing and to remedy cases of impaired healing. Full article

(This article belongs to the Special Issue Biological Cues for Tissue Regeneration and Bioactive Materials)

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19 pages, 6857 KiB

Open AccessArticle

Prediction of Bone Healing around Dental Implants in Various Boundary Conditions by Deep Learning Network

by Pei-Ching Kung, Chia-Wei Hsu, An-Cheng Yang, Nan-Yow Chen and Nien-Ti Tsou

Int. J. Mol. Sci. 2023, 24(3), 1948; https://doi.org/10.3390/ijms24031948 - 18 Jan 2023

Cited by 7 | Viewed by 2340

Abstract

Tissue differentiation varies based on patients’ conditions, such as occlusal force and bone properties. Thus, the design of the implants needs to take these conditions into account to improve osseointegration. However, the efficiency of the design procedure is typically not satisfactory and needs to be significantly improved. Thus, a deep learning network (DLN) is proposed in this study. A data-driven DLN consisting of U-net, ANN, and random forest models was implemented. It serves as a surrogate for finite element analysis and the mechano-regulation algorithm. The datasets include the history of tissue differentiation throughout 35 days with various levels of occlusal force and bone properties. The accuracy of day-by-day tissue differentiation prediction in the testing dataset was 82%, and the AUC value of the five tissue phenotypes (fibrous tissue, cartilage, immature bone, mature bone, and resorption) was above 0.86, showing a high prediction accuracy. The proposed DLN model showed the robustness for surrogating the complex, time-dependent calculations. The results can serve as a design guideline for dental implants. Full article

(This article belongs to the Special Issue Biological Cues for Tissue Regeneration and Bioactive Materials)

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14 pages, 1419 KiB

Open AccessArticle

Directional Submicrofiber Hydrogel Composite Scaffolds Supporting Neuron Differentiation and Enabling Neurite Alignment

by Lena Mungenast, Fabian Züger, Jasmin Selvi, Ana Bela Faia-Torres, Jürgen Rühe, Laura Suter-Dick and Maurizio R. Gullo

Int. J. Mol. Sci. 2022, 23(19), 11525; https://doi.org/10.3390/ijms231911525 - 29 Sep 2022

Cited by 8 | Viewed by 2677

Abstract

Cell cultures aiming at tissue regeneration benefit from scaffolds with physiologically relevant elastic moduli to optimally trigger cell attachment, proliferation and promote differentiation, guidance and tissue maturation. Complex scaffolds designed with guiding cues can mimic the anisotropic nature of neural tissues, such as spinal cord or brain, and recall the ability of human neural progenitor cells to differentiate and align. This work introduces a cost-efficient gelatin-based submicron patterned hydrogel–fiber composite with tuned stiffness, able to support cell attachment, differentiation and alignment of neurons derived from human progenitor cells. The enzymatically crosslinked gelatin-based hydrogels were generated with stiffnesses from 8 to 80 kPa, onto which poly(ε-caprolactone) (PCL) alignment cues were electrospun such that the fibers had a preferential alignment. The fiber–hydrogel composites with a modulus of about 20 kPa showed the strongest cell attachment and highest cell proliferation, rendering them an ideal differentiation support. Differentiated neurons aligned and bundled their neurites along the aligned PCL filaments, which is unique to this cell type on a fiber–hydrogel composite. This novel scaffold relies on robust and inexpensive technology and is suitable for neural tissue engineering where directional neuron alignment is required, such as in the spinal cord. Full article

(This article belongs to the Special Issue Biological Cues for Tissue Regeneration and Bioactive Materials)

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12 pages, 3318 KiB

Open AccessArticle

Visible-Light-Driven Antimicrobial Activity and Mechanism of Polydopamine-Reduced Graphene Oxide/BiVO₄ Composite

by Biyun Li, Xiaoxiao Gao, Jiangang Qu, Feng Xiong, Hongyun Xuan, Yan Jin and Huihua Yuan

Int. J. Mol. Sci. 2022, 23(14), 7712; https://doi.org/10.3390/ijms23147712 - 12 Jul 2022

Cited by 4 | Viewed by 2323

Abstract

In this study, a photocatalytic antibacterial composite of polydopamine-reduced graphene oxide (PDA-rGO)/BiVO₄ is prepared by a hydrothermal self-polymerization reduction method. Its morphology and physicochemical properties are characterized by scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDX), Fourier-transform infrared (FT-IR), and X-ray diffraction (XRD). The results indicate that BiVO₄ particles are evenly distributed on the rGO surface. Escherichia coli (E. coli) MG1655 is selected as the model bacteria, and its antibacterial performance is tested by flat colony counting and the MTT method under light irradiation. PDA-rGO/BiVO₄ inhibits the growth of E. coli under both light and dark conditions, and light significantly enhances the bacteriostasis of PDA-rGO/BiVO₄. A combination of BiVO₄ with PDA-rGO is confirmed by the above characterization methods as improving the photothermal performance under visible light irradiation. The composite possesses enhanced photocatalytic antibacterial activity. Additionally, the photocatalytic antibacterial mechanism is investigated via the morphology changes in the SEM images of MG1655 bacteria, 2′,7′-dichlorofluorescein diacetate (DCFH-DA), the fluorescence detection of the reactive oxygen species (ROS), and gene expression. These results show that PDA-rGO/BiVO₄ can produce more ROS and lead to bacterial death. Subsequently, the q-PCR results show that the transmembrane transport of bacteria is blocked and the respiratory chain is inhibited. This study may provide an important strategy for expanding the application of BiVO₄ in biomedicine and studying the photocatalytic antibacterial mechanism. Full article

(This article belongs to the Special Issue Biological Cues for Tissue Regeneration and Bioactive Materials)

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15 pages, 3600 KiB

Open AccessArticle

In Vitro Monitoring of Magnesium-Based Implants Degradation by Surface Analysis and Optical Spectroscopy

by Hafiz Wajahat Hassan, Maryam Rahmati, Alejandro Barrantes, Håvard Jostein Haugen and Peyman Mirtaheri

Int. J. Mol. Sci. 2022, 23(11), 6099; https://doi.org/10.3390/ijms23116099 - 29 May 2022

Cited by 9 | Viewed by 2933

Abstract

Magnesium (Mg)-based degradable alloys have attracted substantial attention for tissue engineering applications due to their biodegradability and potential for avoiding secondary removal surgeries. However, insufficient data in the existing literature regarding Mg’s corrosion and gas formation after implantation have delayed its wide clinical application. Since the surface properties of degradable materials constantly change after contact with body fluid, monitoring the behaviour of Mg in phantoms or buffer solutions could provide some information about its physicochemical surface changes over time. Through surface analysis and spectroscopic analysis, we aimed to investigate the structural and functional properties of degradable disks. Since bubble formation may lead to inflammation and change pH, monitoring components related to acidosis near the cells is essential. To study the bubble formation in cell culture media, we used a newly developed Mg alloy (based on Mg, zinc, and calcium), pure Mg, and commercially available grade 2 Titanium (Ti) disks in Dulbecco’s Modified Eagle Medium (DMEM) solution to observe their behaviour over ten days of immersion. Using surface analysis and the information from near-infrared spectroscopy (NIRS), we concluded on the conditions associated with the medical risks of Mg alloy disintegration. NIRS is used to investigate the degradation behaviour of Mg-based disks in the cell culture media, which is correlated with the surface analysis where possible. Full article

(This article belongs to the Special Issue Biological Cues for Tissue Regeneration and Bioactive Materials)

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