Biomolecules and Materials Based Approaches in Biomedical Field

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biological and Bio- Materials".

Deadline for manuscript submissions: closed (20 December 2023) | Viewed by 12882

Special Issue Editors


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Guest Editor
National Research Council of Italy, Institute on Membrane Technology, CNR-ITM, Via P. Bucci, Cubo17/C, I-87036 Rende, CS, Italy
Interests: membrane-based approaches for tissue engineering; regenerative medicine and bioartificial organs; 3D membrane tissue models for tissue repair; pharmacological screening; and disease modeling
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Guest Editor
National Research Council of Italy, Institute on Membrane Technology, CNR-ITM, via P. Bucci, cubo 17/C, I-87036 Rende, CS, Italy
Interests: tissue engineering; in vitro platform for disease modeling; membrane devices; biomimetic cell culture systems
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Tissue Engineering Research Laboratory, Bioengineering Department, IQS-School of Engineering, Ramon Llull University, Via Augusta 390, 08017 Barcelona, Spain
Interests: self-assembling peptide scaffolds; tissue engineering; 3D-culture systems; pancreatic cancer organoid model
Special Issues, Collections and Topics in MDPI journals

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Guest Editor
Institute on Membrane Technology (ITM-CNR), National Research Council of Italy, c/o University of Calabria, via P. Bucci cubo 17/C, I-87036 Rende, CS, Italy
Interests: design of micro- and nano-structured membranes; bioengineering of membrane bioreactors, bioartificial organs/tissues; membrane interfacial properties; tissue engineering; in vitro membrane platform
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

To date, biomolecules and materials-based approaches have gained tremendous attention in the biomedical field as they represent advanced strategies that are rapidly transforming the areas of biomedical diagnostics, therapeutics, pharmaceutics, and drug delivery.

Biomolecules range from small molecules, such as amino acids, vitamins, fatty acids, neurotransmitters, and hormones, to macromolecules, which include proteins, carbohydrates, nucleic acids, and enzymes. Intense research activity in the field has highlighted their crucial roles in both biological processes and pathologies. Besides their well known role within the human body, they are potential therapeutic molecules and biomarkers for disease diagnostics, and pharmaceutical development.

Materials-based systems, fabricated in many forms, including films, membranes, tubes, fibers, particles and capsules, nanofiber scaffolds and hydrogels, made of natural, synthetic or blend polymers, and bioreactors, are used in a wide range of biomedical applications. Material characteristics, including morphological, mechanical, physico-chemical, and transport properties, influence the viability, growth, and functions of cells and, consequently, affect new tissue formation. Therefore, the selection of materials plays a key role in the design and development of biomedical products. The challenge is providing biofunctionality, biophysical, mechanical and topographical features of the target tissue in order to improve its repair and regeneration. Currently, different types of materials are used as implants to mimic the structure and function of tissues/organs, organ regeneration, tissue engineering, wound healing, diagnosis of diseases and treatment, and delivery of drugs. Recently, material systems are emerging as investigational tools in preclinical research.

Bioinspired functional material can be developed by the synergistic combination of biomolecules with organic/inorganic materials; indeed, biomolecule-loaded materials, having a greater biocompatibility, are able to promote cell recruitment and attachment leading to the tissue analogue development. Immobilized biomolecules on material surfaces can also act as probes representing a valid platform for early diagnostic detection, representing a promising approach for the building up of very sensitive biosensors.

This Special Issue of Biomolecules aims to provide a comprehensive overview of State-of-the-Art of biomolecules and material-based approaches in biomedical fields; offering to the reader the latest advancements of biomolecules use for different biomedical purposes. We invite research papers that will consolidate our understanding in this area. The Special Issue will publish full research articles and systematic reviews. Potential topics include, but are not limited to, the following research areas:

  • Biomolecules roles in biological processes and pathologies;
  • Therapeutic molecules;
  • Biomarkers;
  • Biomolecules for disease diagnostics, and pharmaceutical development;
  • Cell signaling biomolecules;
  • Biomaterials for biomedical applications;
  • Self-assembled biomaterials;
  • Biofunctionalization of materials;
  • New fabrication technologies (e.g., 3D printing);
  • Biosensors for disease diagnostics and/or prognosis;
  • 3D scaffolds and hydrogels;
  • 3D material-based tissue models;
  • Membrane bioreactors;
  • Bioartificial organs;
  • Materials for cell-/drug-delivery systems;
  • In vitro material platforms for disease modeling/drug screening ;
  • Materials for fabricating microfluidic systems.

Dr. Sabrina Morelli
Dr. Antonella Piscioneri
Dr. Carlos Semino
Dr. Loredana De Bartolo
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

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. Biomolecules 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 2700 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.

Published Papers (5 papers)

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Research

11 pages, 2982 KiB  
Communication
Gelatin-Based Electrospun Nanofibers Cross-Linked Using Horseradish Peroxidase for Plasmid DNA Delivery
by Kotoko Furuno, Keiichiro Suzuki and Shinji Sakai
Biomolecules 2022, 12(11), 1638; https://doi.org/10.3390/biom12111638 - 4 Nov 2022
Cited by 6 | Viewed by 1777
Abstract
The delivery of nucleic acids is indispensable for tissue engineering and gene therapy. However, the current approaches involving DNA/RNA delivery by systemic and local injections face issues such as clearance, off-target distribution, and tissue damage. In this study, we report plasmid DNA (pDNA) [...] Read more.
The delivery of nucleic acids is indispensable for tissue engineering and gene therapy. However, the current approaches involving DNA/RNA delivery by systemic and local injections face issues such as clearance, off-target distribution, and tissue damage. In this study, we report plasmid DNA (pDNA) delivery using gelatin electrospun nanofibers obtained through horseradish peroxidase (HRP)-mediated insolubilization. The nanofibers were obtained through the electrospinning of an aqueous solution containing gelatin possessing phenolic hydroxyl (Ph) moieties (Gelatin-Ph) and HRP with subsequent HRP-mediated cross-linking of the Ph moieties by exposure to air containing 16 ppm H2O2 for 30 min. Then, Lipofectamine/pDNA complexes were immobilized on the nanofibers through immersion in the solution containing the pDNA complexes, resulting in transfection and sustained delivery of pDNA. Cells cultured on the resultant nanofibers expressed genome-editing molecules including Cas9 protein and guide RNA (gRNA), resulting in targeted gene knock-in and knock-out. These results demonstrated the potential of Gelatin-Ph nanofibers obtained through electrospinning and subsequent HRP-mediated cross-linking for gene therapy and tissue regeneration by genome editing. Full article
(This article belongs to the Special Issue Biomolecules and Materials Based Approaches in Biomedical Field)
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17 pages, 3045 KiB  
Article
Coaxial Synthesis of PEI-Based Nanocarriers of Encapsulated RNA-Therapeutics to Specifically Target Muscle Cells
by Raquel de la Hoz, Nazely Diban, María T. Berciano, Carlos San Emeterio, Ane Urtiaga, Miguel Lafarga, José C. Rodríguez-Rey and Olga Tapia
Biomolecules 2022, 12(8), 1012; https://doi.org/10.3390/biom12081012 - 22 Jul 2022
Cited by 5 | Viewed by 2676
Abstract
In this work, we performed a methodological comparative analysis to synthesize polyethyleneimine (PEI) nanoparticles using (i) conventional nanoprecipitation (NP), (ii) electrospraying (ES), and (iii) coaxial electrospraying (CA). The nanoparticles transported antisense oligonucleotides (ASOs), either encapsulated (CA nanocomplexes) or electrostatically bound externally (NP and [...] Read more.
In this work, we performed a methodological comparative analysis to synthesize polyethyleneimine (PEI) nanoparticles using (i) conventional nanoprecipitation (NP), (ii) electrospraying (ES), and (iii) coaxial electrospraying (CA). The nanoparticles transported antisense oligonucleotides (ASOs), either encapsulated (CA nanocomplexes) or electrostatically bound externally (NP and ES nanocomplexes). After synthesis, the PEI/ASO nanoconjugates were functionalized with a muscle-specific RNA aptamer. Using this combinatorial formulation methodology, we obtained nanocomplexes that were further used as nanocarriers for the delivery of RNA therapeutics (ASO), specifically into muscle cells. In particular, we performed a detailed confocal microscopy-based comparative study to analyze the overall transfection efficiency, the cell-to-cell homogeneity, and the mean fluorescence intensity per cell of micron-sized domains enriched with the nanocomplexes. Furthermore, using high-magnification electron microscopy, we were able to describe, in detail, the ultrastructural basis of the cellular uptake and intracellular trafficking of nanocomplexes by the clathrin-independent endocytic pathway. Our results are a clear demonstration that coaxial electrospraying is a promising methodology for the synthesis of therapeutic nanoparticle-based carriers. Some of the principal features that the nanoparticles synthesized by coaxial electrospraying exhibit are efficient RNA-based drug encapsulation, increased nanoparticle surface availability for aptamer functionalization, a high transfection efficiency, and hyperactivation of the endocytosis and early/late endosome route as the main intracellular uptake mechanism. Full article
(This article belongs to the Special Issue Biomolecules and Materials Based Approaches in Biomedical Field)
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13 pages, 896 KiB  
Article
Osteoblast Attachment on Titanium Coated with Hydroxyapatite by Atomic Layer Deposition
by Elina Kylmäoja, Jani Holopainen, Faleh Abushahba, Mikko Ritala and Juha Tuukkanen
Biomolecules 2022, 12(5), 654; https://doi.org/10.3390/biom12050654 - 29 Apr 2022
Cited by 9 | Viewed by 2398
Abstract
Background: The increasing demand for bone implants with improved osseointegration properties has prompted researchers to develop various coating types for metal implants. Atomic layer deposition (ALD) is a method for producing nanoscale coatings conformally on complex three-dimensional surfaces. We have prepared hydroxyapatite (HA) [...] Read more.
Background: The increasing demand for bone implants with improved osseointegration properties has prompted researchers to develop various coating types for metal implants. Atomic layer deposition (ALD) is a method for producing nanoscale coatings conformally on complex three-dimensional surfaces. We have prepared hydroxyapatite (HA) coating on titanium (Ti) substrate with the ALD method and analyzed the biocompatibility of this coating in terms of cell adhesion and viability. Methods: HA coatings were prepared on Ti substrates by depositing CaCO3 films by ALD and converting them to HA by wet treatment in dilute phosphate solution. MC3T3-E1 preosteoblasts were cultured on ALD-HA, glass slides and bovine bone slices. ALD-HA and glass slides were either coated or non-coated with fibronectin. After 48h culture, cells were imaged with scanning electron microscopy (SEM) and analyzed by vinculin antibody staining for focal adhesion localization. An 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) test was performed to study cell viability. Results: Vinculin staining revealed similar focal adhesion-like structures on ALD-HA as on glass slides and bone, albeit on ALD-HA and bone the structures were thinner compared to glass slides. This might be due to thin and broad focal adhesions on complex three-dimensional surfaces of ALD-HA and bone. The MTT test showed comparable cell viability on ALD-HA, glass slides and bone. Conclusion: ALD-HA coating was shown to be biocompatible in regard to cell adhesion and viability. This leads to new opportunities in developing improved implant coatings for better osseointegration and implant survival. Full article
(This article belongs to the Special Issue Biomolecules and Materials Based Approaches in Biomedical Field)
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17 pages, 2931 KiB  
Article
Microtube Array Membrane Hollow Fiber Assay (MTAM-HFA)—An Accurate and Rapid Potential Companion Diagnostic and Pharmacological Interrogation Solution for Cancer Immunotherapy (PD-1/PD-L1)
by Wan-Ting Huang, Tsao Yun, Chee-Ho Chew, Amanda Chen, Po-Li Wei, Kang-Yun Lee, Hsin-Lun Lee, Po-Hao Feng, Jeng-Fong Chiou, Ching-Mei Chen and Chien-Chung Chen
Biomolecules 2022, 12(4), 480; https://doi.org/10.3390/biom12040480 - 22 Mar 2022
Cited by 4 | Viewed by 2467
Abstract
Immunotherapy is one of the most promising forms of cancer treatment. In particular, immune checkpoint blockers (ICBs) represent some of the leading candidates which many drug developers have heavily invested in. During pre-clinical development and prior to human clinical trials, animal tests are [...] Read more.
Immunotherapy is one of the most promising forms of cancer treatment. In particular, immune checkpoint blockers (ICBs) represent some of the leading candidates which many drug developers have heavily invested in. During pre-clinical development and prior to human clinical trials, animal tests are a critical component for determining the safety and efficacy of newly developed ICBs for cancer treatment. In this study, we strive to demonstrate the feasibility of using hollow fiber assay microtube array membrane (MTAM-HFA) in the screening of anti-cancer ICBs. The MTAM-HFA process was carried out by encapsulating peripheral blood mononuclear cells (PBMCs) and the target cancer cells (cell lines or primary cells) and subcutaneously implanting them into Balb/C mice. At predetermined time points combination regimens of PD-1/PD-L1+ were administered accordingly and at a predetermined time point, the MTAMs were retrieved, and cell viability assays were carried out. The outcomes of the MTAM-HFA were compared against the clinical outcome of patients. Clinical comparison demonstrated excellent correlation between the screening outcome of MTAM-HFA of PD-1/PD-L1+ combination therapy and the clinical outcome of the lung cancer patients. Basic cell studies revealed that the utilization of MTAM-HFA in PD-1/PD-L1+ combination therapy revealed enhanced T-cell activity upon the administration of the PD-1/PD-L1 drug; thereby resulting in the reduction of tumor cell viability by up to 70%, and the cytotoxic effects by 82%. The outcome was echoed in the in vivo cell studies. This suggested that the MTAM-HFA system is suitable for use in PD-1/PD-L1+ screening and the accuracy, rapidity and cost effectiveness made it extremely suitable for application as a companion diagnostic system in both personalized medicine for cancer treatment and could potentially be applied to screen for candidate compounds in the development of next generation PD-1/PD-L1+ combination therapies. Full article
(This article belongs to the Special Issue Biomolecules and Materials Based Approaches in Biomedical Field)
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13 pages, 3014 KiB  
Article
β-Sheet to Random Coil Transition in Self-Assembling Peptide Scaffolds Promotes Proteolytic Degradation
by Elsa Genové, Nausika Betriu and Carlos E. Semino
Biomolecules 2022, 12(3), 411; https://doi.org/10.3390/biom12030411 - 7 Mar 2022
Cited by 5 | Viewed by 2487
Abstract
One of the most desirable properties that biomaterials designed for tissue engineering or drug delivery applications should fulfill is biodegradation and resorption without toxicity. Therefore, there is an increasing interest in the development of biomaterials able to be enzymatically degraded once implanted at [...] Read more.
One of the most desirable properties that biomaterials designed for tissue engineering or drug delivery applications should fulfill is biodegradation and resorption without toxicity. Therefore, there is an increasing interest in the development of biomaterials able to be enzymatically degraded once implanted at the injury site or once delivered to the target organ. In this paper, we demonstrate the protease sensitivity of self-assembling amphiphilic peptides, in particular, RAD16-I (AcN-RADARADARADARADA-CONH2), which contains four potential cleavage sites for trypsin. We detected that when subjected to thermal denaturation, the peptide secondary structure suffers a transition from β-sheet to random coil. We also used Matrix-Assisted Laser Desorption/Ionization-Time-Of-Flight (MALDI-TOF) to detect the proteolytic breakdown products of samples subjected to incubation with trypsin as well as atomic force microscopy (AFM) to visualize the effect of the degradation on the nanofiber scaffold. Interestingly, thermally treated samples had a higher extent of degradation than non-denatured samples, suggesting that the transition from β-sheet to random coil leaves the cleavage sites accessible and susceptible to protease degradation. These results indicate that the self-assembling peptide can be reduced to short peptide sequences and, subsequently, degraded to single amino acids, constituting a group of naturally biodegradable materials optimal for their application in tissue engineering and regenerative medicine. Full article
(This article belongs to the Special Issue Biomolecules and Materials Based Approaches in Biomedical Field)
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