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Novel Bioinspired Materials for Biomedical and Biotechnological Applications

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 (31 May 2022) | Viewed by 30402

Special Issue Editor


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Guest Editor
1. Department of Chemistry, Faraday Building, Lancaster University, Lancaster LA1 4YB, UK
2. Materials Science Institute, Faraday Building, Lancaster University, Lancaster LA1 4YB, UK
Interests: polymer synthesis; supramolecular materials; biomaterials; stimuli-responsive materials; drug delivery; tissue engineering; sustainability
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Special Issue Information

Dear Colleagues,

Nature is a practically inexhaustible source of inspiration for the design of synthetic materials. Hence, “bio-inspired materials” is a practically limitless field. In this Special Issue, we will focus on applications in medicine and biotechnology, where materials interact with biological systems, tissues, cells, and microorganisms to invoke the required response in a specific application. For example, we usually do not need microorganism growth in medicine, but we often need it in biotechnology. Characteristics of bio-inspired materials which are relevant for their performance may include, but are not limited to, topographical, chemical, mechanical, and electrical properties. Due to the wide scope of bio-inspired materials, contributions relating to biomaterials, tissue engineering, and biomimetics are also welcome.

Dr. John G. Hardy
Guest Editor

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Keywords

  • biomimetics
  • biocomposites
  • bioinspired
  • biotechnology
  • biomaterials
  • tissue engineering

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Published Papers (10 papers)

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Research

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18 pages, 3507 KiB  
Article
Macropore Regulation of Hydroxyapatite Osteoinduction via Microfluidic Pathway
by Feng Shi, Xin Fang, Teng Zhou, Xu Huang, Ke Duan, Jianxin Wang, Shuxin Qu, Wei Zhi and Jie Weng
Int. J. Mol. Sci. 2022, 23(19), 11459; https://doi.org/10.3390/ijms231911459 - 28 Sep 2022
Cited by 8 | Viewed by 1578
Abstract
Macroporous characteristics have been shown to play a key role in the osteoinductivity of hydroxyapatite ceramics, but the physics underlying the new bone formation and distribution in such scaffolds still remain elusive. The work here has emphasized the osteoinductive capacity of porous hydroxyapatite [...] Read more.
Macroporous characteristics have been shown to play a key role in the osteoinductivity of hydroxyapatite ceramics, but the physics underlying the new bone formation and distribution in such scaffolds still remain elusive. The work here has emphasized the osteoinductive capacity of porous hydroxyapatite scaffolds containing different macroporous sizes (200–400 μm, 1200–1500 μm) and geometries (star shape, spherical shape). The assumption is that both the size and shape of a macropore structure may affect the microfluidic pathways in the scaffolds, which results in the different bone formations and distribution. Herein, a mathematical model and an animal experiment were proposed to support this hypothesis. The results showed that the porous scaffolds with the spherical macropores and large pore sizes (1200–1500 μm) had higher new bone production and more uniform new bone distribution than others. A finite element analysis suggested that the macropore shape affected the distribution of the medium–high velocity flow field, while the macropore size effected microfluid speed and the value of the shear stress in the scaffolds. Additionally, the result of scaffolds implanted into the dorsal muscle having a higher new bone mass than the abdominal cavity suggested that the mechanical load of the host tissue could play a key role in the microfluidic pathway mechanism. All these findings suggested that the osteoinduction of these scaffolds depends on both the microfluid velocity and shear stress generated by the macropore size and shape. This study, therefore, provides new insights into the inherent osteoinductive mechanisms of bioceramics, and may offer clues toward a rational design of bioceramic scaffolds with improved osteoinductivity. Full article
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12 pages, 1570 KiB  
Article
Biological Response to Bioinspired Microporous 3D-Printed Scaffolds for Bone Tissue Engineering
by Mario Ledda, Miriam Merco, Antonio Sciortino, Elisa Scatena, Annalisa Convertino, Antonella Lisi and Costantino Del Gaudio
Int. J. Mol. Sci. 2022, 23(10), 5383; https://doi.org/10.3390/ijms23105383 - 11 May 2022
Cited by 10 | Viewed by 2372
Abstract
The scaffold is a key element in the field of tissue engineering, especially when large defects or substitutions of pathological tissues or organs need to be clinically addressed. The expected outcome is strongly dependent on the cell–scaffold interaction and the integration with the [...] Read more.
The scaffold is a key element in the field of tissue engineering, especially when large defects or substitutions of pathological tissues or organs need to be clinically addressed. The expected outcome is strongly dependent on the cell–scaffold interaction and the integration with the surrounding biological tissue. Indeed, mimicking the natural extracellular matrix (ECM) of the tissue to be healed represents a further optimization that can limit a possible morphological mismatch between the scaffold and the tissue itself. For this aim, and referring to bone tissue engineering, polylactic acid (PLA) scaffolds were 3D printed with a microstructure inspired by the trabecular architecture and biologically evaluated by means of human osteosarcoma SAOS-2 cells. The cells were seeded on two types of scaffolds differing for the designed pore size (i.e., 400 and 600 µm), showing the same growth exponential trend found in the control and no significant alterations in the actin distribution. The microporous structure of the two tested samples enhanced the protein adsorption capability and mRNA expression of markers related to protein synthesis, proliferation, and osteoblast differentiation. Our findings demonstrate that 3D-printed scaffolds support the adhesion, growth, and differentiation of osteoblast-like cells and the microporous architecture, mimicking the natural bone hierarchical structure, and favoring greater bioactivity. These bioinspired scaffolds represent an interesting new tool for bone tissue engineering and regenerative medicine applications. Full article
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14 pages, 2535 KiB  
Article
Hierarchically Structured Surfaces Prepared by Phase Separation: Tissue Mimicking Culture Substrate
by Markéta Kadlečková, Kateřina Skopalová, Barbora Ptošková, Erik Wrzecionko, Eliška Daďová, Karolína Kocourková, Aleš Mráček, Lenka Musilová, Petr Smolka, Petr Humpolíček and Antonín Minařík
Int. J. Mol. Sci. 2022, 23(5), 2541; https://doi.org/10.3390/ijms23052541 - 25 Feb 2022
Cited by 2 | Viewed by 1728
Abstract
The pseudo 3D hierarchical structure mimicking in vivo microenvironment was prepared by phase separation on tissue culture plastic. For surface treatment, time-sequenced dosing of the solvent mixture with various concentrations of polymer component was used. The experiments showed that hierarchically structured surfaces with [...] Read more.
The pseudo 3D hierarchical structure mimicking in vivo microenvironment was prepared by phase separation on tissue culture plastic. For surface treatment, time-sequenced dosing of the solvent mixture with various concentrations of polymer component was used. The experiments showed that hierarchically structured surfaces with macro, meso and micro pores can be prepared with multi-step phase separation processes. Changes in polystyrene surface topography were characterized by atomic force microscopy, scanning electron microscopy and contact profilometry. The cell proliferation and changes in cell morphology were tested on the prepared structured surfaces. Four types of cell lines were used for the determination of impact of the 3D architecture on the cell behavior, namely the mouse embryonic fibroblast, human lung carcinoma, primary human keratinocyte and mouse embryonic stem cells. The increase of proliferation of embryonic stem cells and mouse fibroblasts was the most remarkable. Moreover, the embryonic stem cells express different morphology when cultured on the structured surface. The acquired findings expand the current state of knowledge in the field of cell behavior on structured surfaces and bring new technological procedures leading to their preparation without the use of problematic temporary templates or additives. Full article
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26 pages, 11439 KiB  
Article
Nanoapatites Doped and Co-Doped with Noble Metal Ions as Modern Antibiofilm Materials for Biomedical Applications against Drug-Resistant Clinical Strains of Enterococcus faecalis VRE and Staphylococcus aureus MRSA
by Emil Paluch, Paulina Sobierajska, Piotr Okińczyc, Jarosław Widelski, Anna Duda-Madej, Barbara Krzyżanowska, Paweł Krzyżek, Rafał Ogórek, Jakub Szperlik, Jacek Chmielowiec, Grażyna Gościniak and Rafal J. Wiglusz
Int. J. Mol. Sci. 2022, 23(3), 1533; https://doi.org/10.3390/ijms23031533 - 28 Jan 2022
Cited by 12 | Viewed by 3334
Abstract
The main aim of our research was to investigate antiadhesive and antibiofilm properties of nanocrystalline apatites doped and co-doped with noble metal ions (Ag+, Au+, and Pd2+) against selected drug-resistant strains of Enterococcus faecalis and Staphylococcus aureus [...] Read more.
The main aim of our research was to investigate antiadhesive and antibiofilm properties of nanocrystalline apatites doped and co-doped with noble metal ions (Ag+, Au+, and Pd2+) against selected drug-resistant strains of Enterococcus faecalis and Staphylococcus aureus. The materials with the structure of apatite (hydroxyapatite, nHAp; hydroxy-chlor-apatites, OH-Cl-Ap) containing 1 mol% and 2 mol% of dopants and co-dopants were successfully obtained by the wet chemistry method. The majority of them contained an additional phase of metallic nanoparticles, in particular, AuNPs and PdNPs, which was confirmed by the XRPD, FTIR, UV–Vis, and SEM–EDS techniques. Extensive microbiological tests of the nanoapatites were carried out determining their MIC, MBC value, and FICI. The antiadhesive and antibiofilm properties of the tested nanoapatites were determined in detail with the use of fluorescence microscopy and computer image analysis. The results showed that almost all tested nanoapatites strongly inhibit adhesion and biofilm production of the tested bacterial strains. Biomaterials have not shown any significant cytotoxic effect on fibroblasts and even increased their survival when co-incubated with bacterial biofilms. Performed analyses confirmed that the nanoapatites doped and co-doped with noble metal ions are safe and excellent antiadhesive and antibiofilm biomaterials with potential use in the future in medical sectors. Full article
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22 pages, 3029 KiB  
Article
Self-Similar Functional Circuit Models of Arteries and Deterministic Fractal Operators: Theoretical Revelation for Biomimetic Materials
by Gang Peng, Jianqiao Guo and Yajun Yin
Int. J. Mol. Sci. 2021, 22(23), 12897; https://doi.org/10.3390/ijms222312897 - 29 Nov 2021
Cited by 6 | Viewed by 2428
Abstract
In this paper, the self-similar functional circuit models of arteries are proposed for bioinspired hemodynamic materials design. Based on the mechanical-electrical analogous method, the circuit model can be utilized to mimic the blood flow of arteries. The theoretical mechanism to quantitatively simulate realistic [...] Read more.
In this paper, the self-similar functional circuit models of arteries are proposed for bioinspired hemodynamic materials design. Based on the mechanical-electrical analogous method, the circuit model can be utilized to mimic the blood flow of arteries. The theoretical mechanism to quantitatively simulate realistic blood flow is developed by establishing a fractal circuit network with an infinite number of electrical components. We have found that the fractal admittance operator obtained from the minimum repeating unit of the fractal circuit can simply and directly determine the blood-flow regulation mechanism. Furthermore, according to the operator algebra, the fractal admittance operator on the aorta can be represented by Gaussian-type convolution kernel function. Similarly, the arteriolar operator can be described by Bessel-type function. Moreover, by the self-similar assembly pattern of the proposed model, biomimetic materials which contain self-similar circuits can be designed to mimic physiological or pathological states of blood flow. Studies show that the self-similar functional circuit model can efficiently describe the blood flow and provide an available and convenient structural theoretical revelation for the preparation of in vitro hemodynamic bionic materials. Full article
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16 pages, 4339 KiB  
Article
The Regeneration of Large-Sized and Vascularized Adipose Tissue Using a Tailored Elastic Scaffold and dECM Hydrogels
by Su Hee Kim, Donghak Kim, Misun Cha, Soo Hyun Kim and Youngmee Jung
Int. J. Mol. Sci. 2021, 22(22), 12560; https://doi.org/10.3390/ijms222212560 - 22 Nov 2021
Cited by 12 | Viewed by 2379
Abstract
A dome-shaped elastic poly(l-lactide-co-caprolactone) (PLCL) scaffold with a channel and pore structure was fabricated by a combinative method of 3D printing technology and the gel pressing method (13 mm in diameter and 6.5 mm in thickness) for patient-specific regeneration. [...] Read more.
A dome-shaped elastic poly(l-lactide-co-caprolactone) (PLCL) scaffold with a channel and pore structure was fabricated by a combinative method of 3D printing technology and the gel pressing method (13 mm in diameter and 6.5 mm in thickness) for patient-specific regeneration. The PLCL scaffold was combined with adipose decellularized extracellular matrix (adECM) and heart decellularized extracellular matrix (hdECM) hydrogels and human adipose-derived stem cells (hADSCs) to promote adipogenesis and angiogenesis. These scaffolds had mechanical properties similar to those of native adipose tissue for improved tissue regeneration. The results of the in vitro real-time PCR showed that the dECM hydrogel mixture induces adipogenesis. In addition, the in vivo study at 12 weeks demonstrated that the tissue-engineered PLCL scaffolds containing the hydrogel mixture (hdECM/adECM (80:20)) and hADSCs promoted angiogenesis and adipose tissue formation, and suppressed apoptosis. Therefore, we expect that our constructs will be clinically applicable as material for the regeneration of patient-specific large-sized adipose tissue. Full article
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14 pages, 13499 KiB  
Article
Partial Decellularized Scaffold Combined with Autologous Nasal Epithelial Cell Sheet for Tracheal Tissue Engineering
by Luong Huu Dang, Shih-Han Hung, Yuan Tseng, Ly Xuan Quang, Nhi Thao Ngoc Le, Chia-Lang Fang and How Tseng
Int. J. Mol. Sci. 2021, 22(19), 10322; https://doi.org/10.3390/ijms221910322 - 25 Sep 2021
Cited by 7 | Viewed by 2437
Abstract
Decellularization has emerged as a potential solution for tracheal replacement. As a fully decellularized graft failed to achieve its purposes, the de-epithelialization partial decellularization protocol appeared to be a promising approach for fabricating scaffolds with preserved mechanical properties and few immune rejection responses [...] Read more.
Decellularization has emerged as a potential solution for tracheal replacement. As a fully decellularized graft failed to achieve its purposes, the de-epithelialization partial decellularization protocol appeared to be a promising approach for fabricating scaffolds with preserved mechanical properties and few immune rejection responses after transplantation. Nevertheless, a lack of appropriate concurrent epithelialization treatment can lead to luminal stenosis of the transplant and impede its eventual success. To improve re-epithelialization, autologous nasal epithelial cell sheets generated by our cell sheet engineering platform were utilized in this study under an in vivo rabbit model. The newly created cell sheets have an intact and transplantable appearance, with their specific characteristics of airway epithelial origin being highly expressed upon histological and immunohistochemical analysis. Subsequently, those cell sheets were incorporated with a partially decellularized tracheal graft for autograft transplantation under tracheal partial resection models. The preliminary results two months post operation demonstrated that the transplanted patches appeared to be wholly integrated into the host trachea with adequate healing of the luminal surface, which was confirmed via endoscopic and histologic evaluations. The satisfactory result of this hybrid scaffold protocol could serve as a potential solution for tracheal reconstructions in the future. Full article
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Review

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20 pages, 21613 KiB  
Review
Recent Advances of Microneedles and Their Application in Disease Treatment
by Wenjing Zhang, Wei Zhang, Cairong Li, Jianhua Zhang, Ling Qin and Yuxiao Lai
Int. J. Mol. Sci. 2022, 23(5), 2401; https://doi.org/10.3390/ijms23052401 - 22 Feb 2022
Cited by 16 | Viewed by 5084
Abstract
For decades, scientists have been doing a lot of research and exploration to find effective long-term analgesic and/or disease-modifying treatments. Microneedles (MNs) are a simple, effective, and painless transdermal drug delivery technology that has emerged in recent years, and exhibits great promise for [...] Read more.
For decades, scientists have been doing a lot of research and exploration to find effective long-term analgesic and/or disease-modifying treatments. Microneedles (MNs) are a simple, effective, and painless transdermal drug delivery technology that has emerged in recent years, and exhibits great promise for realizing intelligent drug delivery. With the development of materials science and fabrication technology, the MN transdermal drug delivery technology has been applied and popularized in more and more fields, including chronic illnesses such as arthritis or diabetes, cancer, dermatocosmetology, family planning, and epidemic disease prevention, and has made fruitful achievements. This paper mainly reviews the latest research status of MNs and their fabrication methodology, and summarizes the application of MNs in the treatment of various diseases, as well as the potential to use nanotechnology to develop more intelligent MNs-based drug delivery systems. Full article
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26 pages, 3513 KiB  
Review
Designing Cardiovascular Implants Taking in View the Endothelial Basement Membrane
by Skadi Lau, Manfred Gossen and Andreas Lendlein
Int. J. Mol. Sci. 2021, 22(23), 13120; https://doi.org/10.3390/ijms222313120 - 4 Dec 2021
Cited by 6 | Viewed by 4826
Abstract
Insufficient endothelialization of cardiovascular grafts is a major hurdle in vascular surgery and regenerative medicine, bearing a risk for early graft thrombosis. Neither of the numerous strategies pursued to solve these problems were conclusive. Endothelialization is regulated by the endothelial basement membrane (EBM), [...] Read more.
Insufficient endothelialization of cardiovascular grafts is a major hurdle in vascular surgery and regenerative medicine, bearing a risk for early graft thrombosis. Neither of the numerous strategies pursued to solve these problems were conclusive. Endothelialization is regulated by the endothelial basement membrane (EBM), a highly specialized part of the vascular extracellular matrix. Thus, a detailed understanding of the structure–function interrelations of the EBM components is fundamental for designing biomimetic materials aiming to mimic EBM functions. In this review, a detailed description of the structure and functions of the EBM are provided, including the luminal and abluminal interactions with adjacent cell types, such as vascular smooth muscle cells. Moreover, in vivo as well as in vitro strategies to build or renew EBM are summarized and critically discussed. The spectrum of methods includes vessel decellularization and implant biofunctionalization strategies as well as tissue engineering-based approaches and bioprinting. Finally, the limitations of these methods are highlighted, and future directions are suggested to help improve future design strategies for EBM-inspired materials in the cardiovascular field. Full article
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17 pages, 3333 KiB  
Review
Developing Wound Dressings Using 2-deoxy-D-Ribose to Induce Angiogenesis as a Backdoor Route for Stimulating the Production of Vascular Endothelial Growth Factor
by Serkan Dikici, Muhammad Yar, Anthony J. Bullock, Joanna Shepherd, Sabiniano Roman and Sheila MacNeil
Int. J. Mol. Sci. 2021, 22(21), 11437; https://doi.org/10.3390/ijms222111437 - 23 Oct 2021
Cited by 6 | Viewed by 2723
Abstract
2-deoxy-D-Ribose (2dDR) was first identified in 1930 in the structure of DNA and discovered as a degradation product of it later when the enzyme thymidine phosphorylase breaks down thymidine into thymine. In 2017, our research group explored the development of wound [...] Read more.
2-deoxy-D-Ribose (2dDR) was first identified in 1930 in the structure of DNA and discovered as a degradation product of it later when the enzyme thymidine phosphorylase breaks down thymidine into thymine. In 2017, our research group explored the development of wound dressings based on the delivery of this sugar to induce angiogenesis in chronic wounds. In this review, we will survey the small volume of conflicting literature on this and related sugars, some of which are reported to be anti-angiogenic. We review the evidence of 2dDR having the ability to stimulate a range of pro-angiogenic activities in vitro and in a chick pro-angiogenic bioassay and to stimulate new blood vessel formation and wound healing in normal and diabetic rat models. The biological actions of 2dDR were found to be 80 to 100% as effective as VEGF in addition to upregulating the production of VEGF. We then demonstrated the uptake and delivery of the sugar from a range of experimental and commercial dressings. In conclusion, its pro-angiogenic properties combined with its improved stability on storage compared to VEGF, its low cost, and ease of incorporation into a range of established wound dressings make 2dDR an attractive alternative to VEGF for wound dressing development. Full article
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