Structural and Biomechanical Properties of Supramolecular Nanofibers-Based Hydrogels in Biomedicine

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Nanomedicine and Nanobiology".

Deadline for manuscript submissions: closed (30 June 2022) | Viewed by 21896

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Guest Editor
NeMO Lab., ASST Grande Ospedale Metropolitano Niguarda, 20133 Milan, Italy
Interests: supramolecular hydrogels; nanostructured scaffolds; self-assembling peptides; polymers; nanofibers; nano-nutraceuticals; bioactive materials; regenerative medicine; tissue engineering; neural stem cell
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Special Issue Information

Dear Colleagues,

Supramolecular nanofiber-based hydrogels represent a particularly exciting topic in biomedicine. In the past 20 years, a wide range of nanofibrous scaffolds have been developed, owing to their modularity, ease of modification, and ability to mimic the three-dimensional structure of the native extracellular matrix (ECM) of living tissues. For these reasons, supramolecular nanofibrous hydrogels have become a leading strategy for creating functional biomaterials useful for different applications including (1) three-dimensional cell cultures or organoids of primary and stem cells; (2) the sustained release of drugs, small molecules, bioactive molecules, growth factors, and siRNA; (3) hemostat solutions; (4) fillers or injectable scaffolds for regenerative medicine, as well as tissue engineering; (5) 3D printing; and (6) actuators for optics and fluidics. Furthermore, a few supramolecular hydrogels have been used in clinical trials for wound healing, the treatment of cancers, and surgical use. It is likely that such materials will open doors for different directions in the areas of tissue engineering, synthetic biology, biomedicines, and food-chemistry, to name a few.

Hence, since the field is still expanding at an accelerated pace, in this Special Issue, we aim to collect the latest advances by including biomaterials with improved structural, mechanical, and nano-architectural features for future applications in biomedicine and beyond. Original work is welcome as well as reviews on the field.

Dr. Raffaele Pugliese
Guest Editor

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Keywords

  • supramolecular hydrogels
  • nanofiber scaffold hydrogels
  • nanostructured scaffolds
  • self-assembly
  • bioactive polymers
  • biomaterials
  • 3D printing
  • mechanical properties
  • biomedicine
  • regenerative medicine

Published Papers (9 papers)

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Editorial

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3 pages, 163 KiB  
Editorial
Structural and Biomechanical Properties of Supramolecular Nanofiber-Based Hydrogels in Biomedicine
by Raffaele Pugliese
Biomedicines 2024, 12(1), 205; https://doi.org/10.3390/biomedicines12010205 - 17 Jan 2024
Cited by 1 | Viewed by 581
Abstract
The field of supramolecular nanofiber-based hydrogels in biomedicine has witnessed remarkable growth over the past two decades [...] Full article

Research

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13 pages, 6104 KiB  
Article
De Novo Self-Assembling Peptides Mediate the Conversion of Temozolomide and Delivery of a Model Drug into Glioblastoma Multiforme Cells
by Megan Pitz, Margaret Elpers, Alexandra Nukovic, Sarah Wilde, Arica Jordan Gregory and Angela Alexander-Bryant
Biomedicines 2022, 10(9), 2164; https://doi.org/10.3390/biomedicines10092164 - 02 Sep 2022
Cited by 1 | Viewed by 1403
Abstract
Glioblastoma multiforme (GBM) is the most aggressive central nervous system tumor, and standard treatment, including surgical resection, radiation, and chemotherapy, has not significantly improved patient outcomes over the last 20 years. Temozolomide (TMZ), the prodrug most commonly used to treat GBM, must pass [...] Read more.
Glioblastoma multiforme (GBM) is the most aggressive central nervous system tumor, and standard treatment, including surgical resection, radiation, and chemotherapy, has not significantly improved patient outcomes over the last 20 years. Temozolomide (TMZ), the prodrug most commonly used to treat GBM, must pass the blood–brain barrier and requires a basic pH to convert to its active form. Due to these barriers, less than 30% of orally delivered TMZ reaches the central nervous system and becomes bioactive. In this work, we have developed a novel biomaterial delivery system to convert TMZ to its active form and that shows promise for intracellular TMZ delivery. Self-assembling peptides were characterized under several different assembly conditions and evaluated for TMZ loading and conversion. Both solvent and method of assembly were found to affect the supramolecular and secondary structure of peptide assemblies. Additionally, as peptides degraded in phosphate-buffered saline, TMZ was rapidly converted to its active form. This work demonstrates that peptide-based drug delivery systems can effectively create a local stimulus during drug delivery while remaining biocompatible. This principle could be used in many future biomedical applications in addition to cancer treatment, such as wound healing and regenerative medicine. Full article
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15 pages, 1971 KiB  
Article
A Comparative Evaluation of the Structural and Biomechanical Properties of Food-Grade Biopolymers as Potential Hydrogel Building Blocks
by Adonis Hilal, Anna Florowska, Tomasz Florowski and Małgorzata Wroniak
Biomedicines 2022, 10(9), 2106; https://doi.org/10.3390/biomedicines10092106 - 28 Aug 2022
Cited by 1 | Viewed by 1403
Abstract
The aim of this study was to conduct a comparative assessment of the structural and biomechanical properties of eight selected food-grade biopolymers (pea protein, wheat protein, gellan gum, konjac gum, inulin, maltodextrin, psyllium, and tara gum) as potential hydrogel building blocks. The prepared [...] Read more.
The aim of this study was to conduct a comparative assessment of the structural and biomechanical properties of eight selected food-grade biopolymers (pea protein, wheat protein, gellan gum, konjac gum, inulin, maltodextrin, psyllium, and tara gum) as potential hydrogel building blocks. The prepared samples were investigated in terms of the volumetric gelling index, microrheological parameters, physical stability, and color parameters. Pea protein, gellan gum, konjac gum, and psyllium samples had high VGI values (100%), low solid–liquid balance (SLB < 0.5), and high macroscopic viscosity index (MVI) values (53.50, 59.98, 81.58, and 45.62 nm−2, respectively) in comparison with the samples prepared using wheat protein, maltodextrin, and tara gum (SLB > 0.5, MVI: 13.58, 0.04, and 0.25 nm−2, respectively). Inulin had the highest elasticity index value (31.05 nm−2) and MVI value (590.17 nm−2). The instability index was the lowest in the case of pea protein, gellan gum, konjac gum, and inulin (below 0.02). The color parameters and whiteness index (WI) of each biopolymer differed significantly from one another. Based on the obtained results, pea protein, gellan gum, konjac gum, and psyllium hydrogels had similar structural and biomechanical properties, while inulin hydrogel had the most diverse properties. Wheat protein, maltodextrin, and tara gum did not form a gel structure. Full article
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12 pages, 2190 KiB  
Article
Thixotropic Red Microalgae Sulfated Polysaccharide-Peptide Composite Hydrogels as Scaffolds for Tissue Engineering
by Michal Halperin-Sternfeld, Gal Netanel Liberman, Raha Kannan, Francesca Netti, Peter X. Ma, Shoshana Malis Arad and Lihi Adler-Abramovich
Biomedicines 2022, 10(6), 1388; https://doi.org/10.3390/biomedicines10061388 - 11 Jun 2022
Cited by 12 | Viewed by 2840
Abstract
Sulfated polysaccharides of red marine microalgae have recently gained much attention for biomedical applications due to their anti-inflammatory and antioxidant properties. However, their low mechanical properties limit their use in tissue engineering. Herein, to enhance the mechanical properties of the sulfated polysaccharide produced [...] Read more.
Sulfated polysaccharides of red marine microalgae have recently gained much attention for biomedical applications due to their anti-inflammatory and antioxidant properties. However, their low mechanical properties limit their use in tissue engineering. Herein, to enhance the mechanical properties of the sulfated polysaccharide produced by the red marine microalga, Porphyridium sp. (PS), it was integrated with the fluorenylmethoxycarbonyl diphenylalanine (FmocFF) peptide hydrogelator. Transparent, stable hydrogels were formed when mixing the two components at a 1:1 ratio in three different concentrations. Electron microscopy showed that all hydrogels exhibited a nanofibrous structure, mimicking the extracellular matrix. Furthermore, the hydrogels were injectable, and tunable mechanical properties were obtained by changing the hydrogel concentration. The composite hydrogels allowed the sustained release of curcumin which was controlled by the change in the hydrogel concentration. Finally, the hydrogels supported MC3T3-E1 preosteoblasts viability and calcium deposition. The synergy between the sulfated polysaccharide, with its unique bioactivities, and FmocFF peptide, with its structural and mechanical properties, bears a promising potential for developing novel tunable scaffolds for tissue engineering that may allow cell differentiation into various lineages. Full article
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14 pages, 2345 KiB  
Article
Potential Wound Healing Effect of Gel Based on Chicha Gum, Chitosan, and Mauritia flexuosa Oil
by Maria Onaira Gonçalves Ferreira, Alessandra Braga Ribeiro, Marcia S. Rizzo, Antonia Carla de Jesus Oliveira, Josy Anteveli Osajima, Leticia M. Estevinho and Edson C. Silva-Filho
Biomedicines 2022, 10(4), 899; https://doi.org/10.3390/biomedicines10040899 - 14 Apr 2022
Cited by 6 | Viewed by 2048
Abstract
Wounds are considered a clinically critical issue, and effective treatment will decrease complications, prevent chronic wound formation, and allow rapid healing. The development of products based on naturally occurring materials is an efficient approach to wound healing. Natural polysaccharides can mimic the extracellular [...] Read more.
Wounds are considered a clinically critical issue, and effective treatment will decrease complications, prevent chronic wound formation, and allow rapid healing. The development of products based on naturally occurring materials is an efficient approach to wound healing. Natural polysaccharides can mimic the extracellular matrix and promote cell growth, thus making them attractive for wound healing. In this context, the aim of this work was to produce a gel based on chicha gum, chitosan, and Mauritia flexuosa oil (CGCHO) for wound treatment. TG and DTG analyzed the thermal behavior of the materials, and SEM investigated the surface roughness. The percentages of total phenolic compounds, flavonoids, and antioxidants were determined, presenting a value of 81.811 ± 7.257 µmol gallic acid/g Mauritia flexuosa oil, 57.915 ± 0.305 µmol quercetin/g Mauritia flexuosa oil, and 0.379 mg/mL, respectively. The anti-inflammatory was determined, presenting a value of 10.35 ± 1.46% chicha gum, 16.86 ± 1.00% Mauritia flexuosa oil, 10.17 ± 1.05% CGCHO, and 15.53 ± 0.65% chitosan, respectively. The materials were tested against Gram-negative (Klebsiella pneumoniae) and Gram-positive (Staphylococcus aureus) bacteria and a fungus (Candida albicans). The CGCHO formulation showed better antimicrobial activity against Gram-positive bacteria. In addition, an in vivo wound healing study was also performed. After 21 days of treatment, the epidermal re-epithelialization process was observed. CGCHO showed good thermal stability and roughness that can help in cell growth and promote the tissue healing process. In addition to the good results observed for the antimicrobial, antioxidant, anti-inflammatory activities and providing wound healing, they provided the necessary support for the healing process, thus representing a new approach to the wound healing process. Full article
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11 pages, 2909 KiB  
Article
Gel-Forming of Self-Assembling Peptides Functionalized with Food Bioactive Motifs Modulate DPP-IV and ACE Inhibitory Activity in Human Intestinal Caco-2 Cells
by Raffaele Pugliese, Martina Bartolomei, Carlotta Bollati, Giovanna Boschin, Anna Arnoldi and Carmen Lammi
Biomedicines 2022, 10(2), 330; https://doi.org/10.3390/biomedicines10020330 - 31 Jan 2022
Cited by 11 | Viewed by 2799
Abstract
Food bioactive peptides are increasingly used for formulating food products, nutraceuticals, and functional food, since they are generally considered safe for human consumption and metabolic syndrome prevention. They are also becoming popular as sustainable sources of novel functional biomaterials such as hydrogels, edible [...] Read more.
Food bioactive peptides are increasingly used for formulating food products, nutraceuticals, and functional food, since they are generally considered safe for human consumption and metabolic syndrome prevention. They are also becoming popular as sustainable sources of novel functional biomaterials such as hydrogels, edible nanonutraceuticals, delivery systems, and packing materials. However, such food peptides are mostly unstable, and degrade during food processing, or in a gastrointestinal environment, thus resulting in low bioavailability precluding their practical applications. Here, we decided to functionalize the well-known and characterized self-assembling peptide RADA16 with two synthetic analogues of food bioactive peptides deriving from the hydrolysis of soybean glycinin and lupin β-conglutin (namely IAVPTGVA and LTFPGSAED) for control of and improvement in their gel-forming nanostructures, biomechanics, and biological features. Extensive characterization was performed via Circular Dichroism (CD) spectroscopy, Fourier Transform Infrared spectroscopy (FT-IR), Thioflavin T (ThT) binding assay, rheological measurements, and Atomic Force Microscopy (AFM) analysis. Lastly, since self-assembling peptides (SAPs) can be co-assembled with diluent SAPs (without a bioactive epitope) as an approach to control the density of biological signals and therefore attain enhanced bioactivity, we investigated the effect of the co-assembly of RADA16 and functionalized food bioactive SAPs (dubbed cAP-Soy1 and cAP-Lup1) for the growth of Caco-2 human intestinal cells and contextually we characterized their biological activities as DPP-IV and ACE inhibitors, in order to demonstrate their potential use for the prevention of metabolic syndrome. Full article
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11 pages, 1751 KiB  
Article
Nanostructure, Self-Assembly, Mechanical Properties, and Antioxidant Activity of a Lupin-Derived Peptide Hydrogel
by Raffaele Pugliese, Anna Arnoldi and Carmen Lammi
Biomedicines 2021, 9(3), 294; https://doi.org/10.3390/biomedicines9030294 - 13 Mar 2021
Cited by 12 | Viewed by 3323
Abstract
Naturally occurring food peptides are frequently used in the life sciences due to their beneficial effects through their impact on specific biochemical pathways. Furthermore, they are often leveraged for applications in areas as diverse as bioengineering, medicine, agriculture, and even fashion. However, progress [...] Read more.
Naturally occurring food peptides are frequently used in the life sciences due to their beneficial effects through their impact on specific biochemical pathways. Furthermore, they are often leveraged for applications in areas as diverse as bioengineering, medicine, agriculture, and even fashion. However, progress toward understanding their self-assembling properties as functional materials are often hindered by their long aromatic and charged residue-enriched sequences encrypted in the parent protein sequence. In this study, we elucidate the nanostructure and the hierarchical self-assembly propensity of a lupin-derived peptide which belongs to the α-conglutin (11S globulin, legumin-like protein), with a straightforward N-terminal biotinylated oligoglycine tag-based methodology for controlling the nanostructures, biomechanics, and biological features. Extensive characterization was performed via Circular Dichroism (CD) spectroscopy, Fourier Transform Infrared spectroscopy (FT-IR), rheological measurements, and Atomic Force Microscopy (AFM) analyses. By using the biotin tag, we obtained a thixotropic lupin-derived peptide hydrogel (named BT13) with tunable mechanical properties (from 2 to 11 kPa), without impairing its spontaneous formation of β-sheet secondary structures. Lastly, we demonstrated that this hydrogel has antioxidant activity. Altogether, our findings address multiple challenges associated with the development of naturally occurring food peptide-based hydrogels, offering a new tool to both fine tune the mechanical properties and tailor the antioxidant activities, providing new research directions across food chemistry, biochemistry, and bioengineering. Full article
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Review

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22 pages, 3441 KiB  
Review
Tissue Engineering as a Promising Treatment for Glottic Insufficiency: A Review on Biomolecules and Cell-Laden Hydrogel
by Wan-Chiew Ng, Yogeswaran Lokanathan, Marina Mat Baki, Mh Busra Fauzi, Ani Amelia Zainuddin and Mawaddah Azman
Biomedicines 2022, 10(12), 3082; https://doi.org/10.3390/biomedicines10123082 - 30 Nov 2022
Cited by 2 | Viewed by 1729
Abstract
Glottic insufficiency is widespread in the elderly population and occurs as a result of secondary damage or systemic disease. Tissue engineering is a viable treatment for glottic insufficiency since it aims to restore damaged nerve tissue and revitalize aging muscle. After injection into [...] Read more.
Glottic insufficiency is widespread in the elderly population and occurs as a result of secondary damage or systemic disease. Tissue engineering is a viable treatment for glottic insufficiency since it aims to restore damaged nerve tissue and revitalize aging muscle. After injection into the biological system, injectable biomaterial delivers cost- and time-effectiveness while acting as a protective shield for cells and biomolecules. This article focuses on injectable biomaterials that transport cells and biomolecules in regenerated tissue, particularly adipose, muscle, and nerve tissue. We propose Wharton’s Jelly mesenchymal stem cells (WJMSCs), induced pluripotent stem cells (IP-SCs), basic fibroblast growth factor (bFGF), vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), insulin growth factor-1 (IGF-1) and extracellular vesicle (EV) as potential cells and macromolecules to be included into biomaterials, with some particular testing to support them as a promising translational medicine for vocal fold regeneration. Full article
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27 pages, 4249 KiB  
Review
A Review of Sustained Drug Release Studies from Nanofiber Hydrogels
by Ilker S. Bayer
Biomedicines 2021, 9(11), 1612; https://doi.org/10.3390/biomedicines9111612 - 04 Nov 2021
Cited by 24 | Viewed by 4723
Abstract
Polymer nanofibers have exceptionally high surface area. This is advantageous compared to bulk polymeric structures, as nanofibrils increase the area over which materials can be transported into and out of a system, via diffusion and active transport. On the other hand, since hydrogels [...] Read more.
Polymer nanofibers have exceptionally high surface area. This is advantageous compared to bulk polymeric structures, as nanofibrils increase the area over which materials can be transported into and out of a system, via diffusion and active transport. On the other hand, since hydrogels possess a degree of flexibility very similar to natural tissue, due to their significant water content, hydrogels made from natural or biodegradable macromolecular systems can even be injectable into the human body. Due to unique interactions with water, hydrogel transport properties can be easily modified and tailored. As a result, combining nanofibers with hydrogels would truly advance biomedical applications of hydrogels, particularly in the area of sustained drug delivery. In fact, certain nanofiber networks can be transformed into hydrogels directly without the need for a hydrogel enclosure. This review discusses recent advances in the fabrication and application of biomedical nanofiber hydrogels with a strong emphasis on drug release. Most of the drug release studies and recent advances have so far focused on self-gelling nanofiber systems made from peptides or other natural proteins loaded with cancer drugs. Secondly, polysaccharide nanofiber hydrogels are being investigated, and thirdly, electrospun biodegradable polymer networks embedded in polysaccharide-based hydrogels are becoming increasingly popular. This review shows that a major outcome from these works is that nanofiber hydrogels can maintain drug release rates exceeding a few days, even extending into months, which is an extremely difficult task to achieve without the nanofiber texture. This review also demonstrates that some publications still lack careful rheological studies on nanofiber hydrogels; however, rheological properties of hydrogels can influence cell function, mechano-transduction, and cellular interactions such as growth, migration, adhesion, proliferation, differentiation, and morphology. Nanofiber hydrogel rheology becomes even more critical for 3D or 4D printable systems that should maintain sustained drug delivery rates. Full article
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