Special Issue "Tissue Engineered Biomaterials and Drug Delivery Systems"

A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Drug Delivery and Controlled Release".

Deadline for manuscript submissions: 20 March 2022.

Special Issue Editors

Dr. Viviana Pinto Ribeiro
E-Mail Website
Guest Editor
1. 3B’s Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics of University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark - Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco Guimarães, Portugal
2. ICVS/3B’s - PT Government Associate Laboratory, 4805-017 Braga/Guimarães, Portugal
Interests: biomaterials; silk fibroin; osteochondral; bone; cartilage; tissue engineering; regenerative medicine; 3D in vitro modeling; cancer
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Joaquim Miguel Oliveira
E-Mail Website
Guest Editor
1. 3B’s Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics of University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark - Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal
2. ICVS/3B’s - PT Government Associate Laboratory, 4805-017 Braga/Guimarães, Portugal
Interests: nanobiomaterials; nanomedicine; theranostics; tissue engineering; bio 3D printing; 3D in vitro tissue models of disease
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Rui L. Reis
E-Mail Website
Guest Editor
1. 3B’s Research Group, I3Bs - Research Institute on Biomaterials, Biodegradables and Biomimetics of University of Minho, Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Avepark - Parque de Ciência e Tecnologia, Zona Industrial da Gandra, 4805-017 Barco, Guimarães, Portugal
2. ICVS/3B’s - PT Government Associate Laboratory, 4805-017 Braga/Guimarães, Portugal
Interests: natural origin materials; tissue engineering; regenerative medicine; stem cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Recent advances in biomaterials engineering for drug delivery have allowed significant progress in the biomedical field. Tissue engineers, in collaboration with physical scientists, biologists, and clinicians, are responsible for such developments by creating innovative strategies, medical devices, and advanced technologies capable of addressing a higher number of patients requirements. Biomaterials applied for anti-cancer drugs delivery, cancer immunotherapy, autoimmune diseases, neurodegenerative diseases, and genome editing are some of the major innovations that are being explored and developed. The possibility of combining biomaterials and drug delivery in precision medicine strategies is attractive and likely to directly meet patients’ specific needs. Responsive biomaterials incorporating nanocarriers or multimodal nanoprobes are being used for cell/organ targeting, intracellular drug delivery, and gene therapy. Aiming to explore these concepts, this Special Issue will focus on recent tissue-engineered biomaterials developed for drug delivery in biomedical applications, discussing emerging scaffolding strategies and processing technologies, nano-based drug delivery sytems and applied nanobiomaterials, material–cell interactions, and drug delivery efficiency. We kindly invite you to submit a manuscript(s) for this Special Issue. Full papers, communications, and reviews are all welcome.

 

Submissions can cover the following topics (but are not limited to them):

- Biomaterials as artificial extracellular matrices;

- Bioactive natural-based carriers for drug delivery;

- Nanobiomaterials for controlled and targeted drug delivery;

- Hydrogels for drug/cell delivery and imaging;

- Microfluidic devices for drug delivery systems;

- DNA nanotechnology-enabling drug delivery systems;

- Processing of biopolymers for drug delivery systems;

- 3D printing and drug delivery devices;

- In vitro 3D models for nanomedicine testing and personalized medicine

Dr. Viviana Pinto Ribeiro
Prof. Dr. Joaquim Miguel Oliveira
Prof. Dr. Rui L. Reis
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 papers will be 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. Pharmaceutics 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

  • tissue engineering
  • regenerative medicine
  • biopolymers
  • drug delivery
  • nano-based drug delivery
  • nanotechnology
  • precision medicine
  • nanobiomaterials
  • microfluidics
  • scaffolding strategies
  • 3D printing
  • 3D in vitro models

Published Papers (5 papers)

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Research

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Article
Cellulose Nanofiber-Based Hydrogels Embedding 5-FU Promote Pyroptosis Activation in Breast Cancer Cells and Support Human Adipose-Derived Stem Cell Proliferation, Opening New Perspectives for Breast Tissue Engineering
Pharmaceutics 2021, 13(8), 1189; https://doi.org/10.3390/pharmaceutics13081189 - 01 Aug 2021
Cited by 1 | Viewed by 985
Abstract
The structure and biocompatibility analysis of a hydrogel based on cellulose nanofibers (CNFs) combined with alginate/pectin (A.CNF or P.CNF) and enriched with 1% or 5% 5-FU revealed more favorable properties for the cellular component when pectin was dispersed within CNFs. 5-Fluorouracil (5-FU) is [...] Read more.
The structure and biocompatibility analysis of a hydrogel based on cellulose nanofibers (CNFs) combined with alginate/pectin (A.CNF or P.CNF) and enriched with 1% or 5% 5-FU revealed more favorable properties for the cellular component when pectin was dispersed within CNFs. 5-Fluorouracil (5-FU) is an antimetabolite fluoropyrimidine used as antineoplastic drug for the treatment of multiple solid tumors. 5-FU activity leads to caspase-1 activation, secretion and maturation of interleukins (IL)-1, IL-18 and reactive oxygen species (ROS) generation. Furthermore, the effects of embedding 5-FU in P.CNF were explored in order to suppress breast tumor cell growth and induce inflammasome complex activation together with extra- and intracellular ROS generation. Exposure of tumor cells to P.CNF/5-FU resulted in a strong cytotoxic effect, an increased level of caspase-1 released in the culture media and ROS production—the latter directly proportional to the concentration of anti-tumor agent embedded in the scaffolds. Simultaneously, 5-FU determined the increase of p53 and caspase-1 expressions, both at gene and protein levels. In conclusion, P.CNF/5-FU scaffolds proved to be efficient against breast tumor cells growth due to pyroptosis induction. Furthermore, biocompatibility and the potential to support human adipose-derived stem cell growth were demonstrated, suggesting that these 3D systems could be used in soft tissue reconstruction post-mastectomy. Full article
(This article belongs to the Special Issue Tissue Engineered Biomaterials and Drug Delivery Systems)
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Article
Bioengineered Nanoparticles Loaded-Hydrogels to Target TNF Alpha in Inflammatory Diseases
Pharmaceutics 2021, 13(8), 1111; https://doi.org/10.3390/pharmaceutics13081111 - 21 Jul 2021
Viewed by 948
Abstract
Rheumatoid Arthritis (RA) is an incurable autoimmune disease that promotes the chronic impairment of patients’ mobility. For this reason, it is vital to develop therapies that target early inflammatory symptoms and act before permanent articular damage. The present study offers two novel therapies [...] Read more.
Rheumatoid Arthritis (RA) is an incurable autoimmune disease that promotes the chronic impairment of patients’ mobility. For this reason, it is vital to develop therapies that target early inflammatory symptoms and act before permanent articular damage. The present study offers two novel therapies based in advanced drug delivery systems for RA treatment: encapsulated chondroitin sulfate modified poly(amidoamine) dendrimer nanoparticles (NPs) covalently bonded to monoclonal anti-TNF α antibody in both Tyramine-Gellan Gum and Tyramine-Gellan Gum/Silk Fibroin hydrogels. Using pro-inflammatory THP-1 (i.e., human monocytic cell line), the therapy was tested in an inflammation in vitro model under both static and dynamic conditions. Firstly, we demonstrated effective NP-antibody functionalization and TNF-α capture. Upon encapsulation, the NPs were released steadily over 21 days. Moreover, in static conditions, the approaches presented good anti-inflammatory activity over time, enabling the retainment of a high percentage of TNF α. To mimic the physiological conditions of the human body, the hydrogels were evaluated in a dual-chamber bioreactor. Dynamic in vitro studies showed absent cytotoxicity in THP-1 cells and a significant reduction of TNF-α in suspension over 14 days for both hydrogels. Thus, the developed approach showed potential for use as personalized medicine to obtain better therapeutic outcomes and decreased adverse effects. Full article
(This article belongs to the Special Issue Tissue Engineered Biomaterials and Drug Delivery Systems)
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Article
Self-Encapsulation of Biomacromolecule Drugs in Porous Microscaffolds with Aqueous Two-Phase Systems
Pharmaceutics 2021, 13(3), 426; https://doi.org/10.3390/pharmaceutics13030426 - 22 Mar 2021
Viewed by 658
Abstract
At present, the most commonly used methods of microencapsulation of protein drugs such as spray drying, multiple emulsification, and phase separation, can easily cause the problem of protein instability, which leads to low bioavailability and uncontrolled release of protein drugs. Herein, a novel [...] Read more.
At present, the most commonly used methods of microencapsulation of protein drugs such as spray drying, multiple emulsification, and phase separation, can easily cause the problem of protein instability, which leads to low bioavailability and uncontrolled release of protein drugs. Herein, a novel method to encapsulate protein drugs into porous microscaffolds effectively and stably was described. Ammonium hydrogen carbonate (NH4HCO3) was employed to prepare porous microscaffolds. α-Amylase was encapsulated into the porous microscaffolds without denaturing conditions by an aqueous two-phase system (PEG/Sulfate). The pores were closed by heating above the glass transition temperature to achieve a sustained release of microscaffolds. The pore-closed microscaffolds were characterized and released in vitro. The integrity and activity of protein drugs were investigated to verify that this method was friendly to protein drugs. Results showed that the pores were successfully closed and a high loading amount of 9.67 ± 6.28% (w/w) was achieved. The pore-closed microscaffolds released more than two weeks without initial burst, and a high relative activity (92% compared with native one) of protein demonstrated the feasibility of this method for protein drug encapsulation and delivery. Full article
(This article belongs to the Special Issue Tissue Engineered Biomaterials and Drug Delivery Systems)
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Article
Chondrogenic Commitment of Human Bone Marrow Mesenchymal Stem Cells in a Perfused Collagen Hydrogel Functionalized with hTGF-β1-Releasing PLGA Microcarrier
Pharmaceutics 2021, 13(3), 399; https://doi.org/10.3390/pharmaceutics13030399 - 17 Mar 2021
Cited by 5 | Viewed by 1675
Abstract
Tissue engineering strategies can be relevant for cartilage repair and regeneration. A collagen matrix was functionalized with the addition of poly-lactic-co-glycolic acid microcarriers (PLGA-MCs) carrying a human Transforming Growth Factor β1 (hTFG-β1) payload, to provide a 3D biomimetic environment with the capacity to [...] Read more.
Tissue engineering strategies can be relevant for cartilage repair and regeneration. A collagen matrix was functionalized with the addition of poly-lactic-co-glycolic acid microcarriers (PLGA-MCs) carrying a human Transforming Growth Factor β1 (hTFG-β1) payload, to provide a 3D biomimetic environment with the capacity to direct stem cell commitment towards a chondrogenic phenotype. PLGA-MCs (mean size 3 ± 0.9 μm) were prepared via supercritical emulsion extraction technology and tailored to sustain delivery of payload into the collagen hydrogel for 21 days. PLGA-MCs were coseeded with human Bone Marrow Mesenchymal Stem Cells (hBM-MSCs) in the collagen matrix. Chondrogenic induction was suggested when dynamic perfusion was applied as indicated by transcriptional upregulation of COL2A1 gene (5-fold; p < 0.01) and downregulation of COL1A1 (0.07-fold; p < 0.05) and COL3A1 (0.11-fold; p < 0.05) genes, at day 16, as monitored by qRT-PCR. Histological and quantitative-immunofluorescence (qIF) analysis confirmed cell activity by remodeling the synthetic extracellular matrix when cultured in perfused conditions. Static constructs lacked evidence of chondrogenic specific gene overexpression, which was probably due to a reduced mass exchange, as determined by 3D system Finite Element Modelling (FEM) analysis. Proinflammatory (IL-6, TNF, IL-12A, IL-1β) and anti-inflammatory (IL-10, TGF-β1) cytokine gene expression by hBM-MSC was observed only in dynamic culture (TNF and IL-1β 10-fold, p < 0.001; TGF-β1 4-fold, p < 0.01 at Day 16) confirming the cells’ immunomodulatory activity mainly in relation to their commitment and not due to the synthetic environment. This study supports the use of 3D hydrogel scaffolds, equipped for growth factor controlled delivery, as tissue engineered models for the study of in vitro chondrogenic differentiation and opens clinical perspectives for injectable collagen-based advanced therapy systems. Full article
(This article belongs to the Special Issue Tissue Engineered Biomaterials and Drug Delivery Systems)
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Review

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Review
Hydroxyapatite Nanoparticles in Drug Delivery: Physicochemistry and Applications
Pharmaceutics 2021, 13(10), 1642; https://doi.org/10.3390/pharmaceutics13101642 - 09 Oct 2021
Viewed by 570
Abstract
Hydroxyapatite (HAP) has been the gold standard in the biomedical field due to its composition and similarity to human bone. Properties such as shape, size, morphology, and ionic substitution can be tailored through the use of different synthesis techniques and compounds. Regardless of [...] Read more.
Hydroxyapatite (HAP) has been the gold standard in the biomedical field due to its composition and similarity to human bone. Properties such as shape, size, morphology, and ionic substitution can be tailored through the use of different synthesis techniques and compounds. Regardless of the ability to determine its physicochemical properties, a conclusion for the correlation with the biological response it is yet to be found. Hence, a special focus on the most desirable properties for an appropriate biological response needs to be addressed. This review provides an overview of the fundamental properties of hydroxyapatite nanoparticles and the characterization of physicochemical properties involved in their biological response and role as a drug delivery system. A summary of the main chemical properties and applications of hydroxyapatite, the advantages of using nanoparticles, and the influence of shape, size, functional group, morphology, and crystalline phase in the biological response is presented. A special emphasis was placed on the analysis of chemical and physical interactions of the nanoparticles and the cargo, which was explained through the use of spectroscopic and physical techniques such as FTIR, Raman, XRD, SEM, DLS, and BET. We discuss the properties tailored for hydroxyapatite nanoparticles for a specific biomolecule based on the compilation of studies performed on proteins, peptides, drugs, and genetic material. Full article
(This article belongs to the Special Issue Tissue Engineered Biomaterials and Drug Delivery Systems)
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