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: closed (30 June 2022) | Viewed by 39492

Special Issue Editors


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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

E-Mail Website
Guest Editor
1. 3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, 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, Barco, 4805-017 Guimarães, Portugal
2. ICVS/3B’s–PT Government Associate Laboratory, Braga, 4805-017 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

E-Mail Website
Guest Editor
1. 3B’s Research Group, I3Bs—Research Institute on Biomaterials, Biodegradables and Biomimetics, 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, Barco, 4805-017 Guimarães, Portugal
2. ICVS/3B’s–PT Government Associate Laboratory, Braga, 4805-017 Guimarães, Portugal
Interests: tissue engineering; regenerative medicine; biomaterials; biomimetics; biodegradable materials; 3D in vitro models; cancer modelling
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 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. 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 2900 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 (12 papers)

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Editorial

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4 pages, 199 KiB  
Editorial
Special Issue: Tissue Engineered Biomaterials and Drug Delivery Systems
by Viviana P. Ribeiro, Joaquim M. Oliveira and Rui L. Reis
Pharmaceutics 2022, 14(12), 2827; https://doi.org/10.3390/pharmaceutics14122827 - 16 Dec 2022
Viewed by 1231
Abstract
Current advances in biomaterials processing and engineering for drug delivery have allowed interesting progressed in biomedical field [...] Full article
(This article belongs to the Special Issue Tissue Engineered Biomaterials and Drug Delivery Systems)

Research

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12 pages, 2081 KiB  
Article
Glial Cell Line-Derived Neurotrophic Factor-Loaded CMCht/PAMAM Dendrimer Nanoparticles for Peripheral Nerve Repair
by Ane Escobar, Mariana R. Carvalho, F. Raquel Maia, Rui L. Reis, Tiago H. Silva and Joaquim M. Oliveira
Pharmaceutics 2022, 14(11), 2408; https://doi.org/10.3390/pharmaceutics14112408 - 08 Nov 2022
Cited by 1 | Viewed by 1816
Abstract
(1) Background: Peripheral nerve injuries represent a major clinical challenge. If nerve ends retract, there is no spontaneous regeneration and grafts are required to proximate the nerve ends and give continuity to the nerve. (2) Methods: GDNF-loaded NPs were characterized physicochemically. For that, [...] Read more.
(1) Background: Peripheral nerve injuries represent a major clinical challenge. If nerve ends retract, there is no spontaneous regeneration and grafts are required to proximate the nerve ends and give continuity to the nerve. (2) Methods: GDNF-loaded NPs were characterized physicochemically. For that, NPs stability at different pH’s was assessed, and GDNF release was studied through ELISA. In vitro studies are performed with Schwann cells, and the NPs are labeled with fluorescein-5(6)-isothiocyanate for uptake experiments with SH-SY5Y neural cells. (3) Results: GDNF-loaded NPs are stable in physiological conditions, releasing GDNF in a two-step profile, which is beneficial for nerve repair. Cell viability is improved after 1 day of culture, and the uptake is near 99.97% after 3 days of incubation. (4) Conclusions: The present work shows the efficiency of using CMCht/PAMAM NPs as a GDNF-release system to act on peripheral nerve regeneration. Full article
(This article belongs to the Special Issue Tissue Engineered Biomaterials and Drug Delivery Systems)
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18 pages, 5707 KiB  
Article
Biomaterial-Mediated Protein Expression Induced by Peptide-mRNA Nanoparticles Embedded in Lyophilized Collagen Scaffolds
by Rik Oude Egberink, Helen M. Zegelaar, Najoua El Boujnouni, Elly M. M. Versteeg, Willeke F. Daamen and Roland Brock
Pharmaceutics 2022, 14(8), 1619; https://doi.org/10.3390/pharmaceutics14081619 - 02 Aug 2022
Cited by 9 | Viewed by 2503
Abstract
In our aging society, the number of patients suffering from poorly healing bone defects increases. Bone morphogenetic proteins (BMPs) are used in the clinic to promote bone regeneration. However, poor control of BMP delivery and thus activity necessitates high doses, resulting in adverse [...] Read more.
In our aging society, the number of patients suffering from poorly healing bone defects increases. Bone morphogenetic proteins (BMPs) are used in the clinic to promote bone regeneration. However, poor control of BMP delivery and thus activity necessitates high doses, resulting in adverse effects and increased costs. It has been demonstrated that messenger RNA (mRNA) provides a superior alternative to protein delivery due to local uptake and prolonged expression restricted to the site of action. Here, we present the development of porous collagen scaffolds incorporating peptide-mRNA nanoparticles (NPs). Nanoparticles were generated by simply mixing aqueous solutions of the cationic cell-penetrating peptide PepFect14 (PF14) and mRNA. Peptide-mRNA complexes were uniformly distributed throughout the scaffolds, and matrices fully preserved cell attachment and viability. There was a clear dependence of protein expression on the incorporated amount of mRNA. Importantly, after lyophilization, the mRNA formulation in the collagen scaffolds retained activity also at 4 °C over two weeks. Overall, our results demonstrate that collagen scaffolds incorporating peptide-mRNA complexes hold promise as off-the-shelf functional biomaterials for applications in regenerative medicine and constitute a viable alternative to lipid-based mRNA formulations. Full article
(This article belongs to the Special Issue Tissue Engineered Biomaterials and Drug Delivery Systems)
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17 pages, 4346 KiB  
Article
3D-Printed Gentamicin-Releasing Poly-ε-Caprolactone Composite Prevents Fracture-Related Staphylococcus aureus Infection in Mice
by Clara Guarch-Pérez, Bahaa Shaqour, Martijn Riool, Bart Verleije, Koen Beyers, Chris Vervaet, Paul Cos and Sebastian A. J. Zaat
Pharmaceutics 2022, 14(7), 1363; https://doi.org/10.3390/pharmaceutics14071363 - 28 Jun 2022
Cited by 9 | Viewed by 2717
Abstract
Bacterial infections are a serious healthcare complication in orthopedic and trauma surgery worldwide. Compared to systemic, local antibiotic prophylaxis has been shown to provide a higher antibiotic dose and bioavailability at the bone site with minimum toxic effects. However, there are still not [...] Read more.
Bacterial infections are a serious healthcare complication in orthopedic and trauma surgery worldwide. Compared to systemic, local antibiotic prophylaxis has been shown to provide a higher antibiotic dose and bioavailability at the bone site with minimum toxic effects. However, there are still not enough biomaterial and antibiotic combinations available for personalized implant sizes for patients. The aim of this study was to develop a bone fixation plate coating made of a composite of poly-ε-caprolactone, hydroxyapatite and halloysite nanotubes loaded with gentamicin sulphate and fabricated via fused filament fabrication 3D printing technology. The mechanical and thermal properties of the biomaterial were analyzed. The in vitro release kinetics of gentamicin sulphate were evaluated for 14 days showing a burst release during the first two days that was followed by a sustained release of bactericidal concentrations. The composite loaded with 2 and 5% gentamicin sulphate exhibited complete antimicrobial killing of Staphylococcus aureus in an ex vivo mouse femur fixation plate infection model. Moreover, a fixation plate of the composite loaded with 5% of gentamicin sulphate was able to prevent S. aureus infection in the bone and surrounding tissue in an in vivo mouse bone fixation plate infection model 3 days post-surgery. In conclusion, the newly developed composite material successfully prevented infection in vivo. Additionally, the ability to use fused filament fabrication 3D printing to produce patient-specific implants may provide a wider range of personalized solutions for patients. Full article
(This article belongs to the Special Issue Tissue Engineered Biomaterials and Drug Delivery Systems)
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22 pages, 2778 KiB  
Article
Bioinspired Silk Fibroin-Based Composite Grafts as Bone Tunnel Fillers for Anterior Cruciate Ligament Reconstruction
by Viviana P. Ribeiro, João B. Costa, Sofia M. Carneiro, Sandra Pina, Ana C. A. Veloso, Rui L. Reis and Joaquim M. Oliveira
Pharmaceutics 2022, 14(4), 697; https://doi.org/10.3390/pharmaceutics14040697 - 24 Mar 2022
Cited by 9 | Viewed by 2761
Abstract
Anterior cruciate ligament (ACL) replacement is still a big challenge in orthopedics due to the need to develop bioinspired implants that can mimic the complexity of bone-ligament interface. In this study, we propose biomimetic composite tubular grafts (CTGs) made of horseradish peroxidase (HRP)-cross-linked [...] Read more.
Anterior cruciate ligament (ACL) replacement is still a big challenge in orthopedics due to the need to develop bioinspired implants that can mimic the complexity of bone-ligament interface. In this study, we propose biomimetic composite tubular grafts (CTGs) made of horseradish peroxidase (HRP)-cross-linked silk fibroin (SF) hydrogels containing ZnSr-doped β-tricalcium phosphate (ZnSr-β-TCP) particles, as promising bone tunnel fillers to be used in ACL grafts (ACLGs) implantation. For comparative purposes, plain HRP-cross-linked SF hydrogels (PTGs) were fabricated. Sonication and freeze-drying methodologies capable of inducing crystalline β-sheet conformation were carried out to produce both the CTGs and PTGs. A homogeneous microstructure was achieved from microporous to nanoporous scales. The mechanical properties were dependent on the inorganic powder’s incorporation, with a superior tensile modulus observed on the CTGs (12.05 ± 1.03 MPa) as compared to the PTGs (5.30 ± 0.93 MPa). The CTGs presented adequate swelling properties to fill the space in the bone structure after bone tunnel enlargement and provide a stable degradation profile under low concentration of protease XIV. The in vitro studies revealed that SaOs-2 cells adhered, proliferated and remained viable when cultured into the CTGs. In addition, the bioactive CTGs supported the osteogenic activity of cells in terms of alkaline phosphatase (ALP) production, activity, and relative gene expression of osteogenic-related markers. Therefore, this study is the first evidence that the developed CTGs hold adequate structural, chemical, and biological properties to be used as bone tunnel fillers capable of connecting to the ACL tissue while stimulating bone tissue regeneration for a faster osteointegration. Full article
(This article belongs to the Special Issue Tissue Engineered Biomaterials and Drug Delivery Systems)
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14 pages, 1492 KiB  
Article
Enhanced Anticancer Activity of Nedaplatin Loaded onto Copper Nanoparticles Synthesized Using Red Algae
by Nada Mostafa Aboeita, Sherif Ashraf Fahmy, Mayyada M. H. El-Sayed, Hassan Mohamed El-Said Azzazy and Tamer Shoeib
Pharmaceutics 2022, 14(2), 418; https://doi.org/10.3390/pharmaceutics14020418 - 15 Feb 2022
Cited by 28 | Viewed by 3533
Abstract
Marine algae are a rich source of biologically active compounds that can be utilized in various food and pharmaceutical applications. In this study, ultrasound-assisted extraction (UAE) was optimized to maximize yield and total carbohydrate content extracted from the red algae, Pterocladia capillacea. [...] Read more.
Marine algae are a rich source of biologically active compounds that can be utilized in various food and pharmaceutical applications. In this study, ultrasound-assisted extraction (UAE) was optimized to maximize yield and total carbohydrate content extracted from the red algae, Pterocladia capillacea. The extract was shown to possess potent antioxidant activity of up to ~70%, and was successfully used as a reducing and capping agent in the green synthesis of copper nanoparticles, which were characterized by UV-spectroscopy, Fourier transform infrared (FTIR) spectroscopy, X-ray diffraction (XRD), transmission electron microscopy (TEM), and dynamic light scattering (DLS). Primarily, CuO nanoparticles with an average size of 62 nm were produced. FTIR spectra for the extract and algal-mediated CuO nanoparticles showed characteristic polysaccharide peaks. The synthesized CuO nanoparticles were subsequently loaded with nedaplatin where UV data suggested a complex formation. Nedaplatin release profiles showed a sustained release that reached a maximum at 120 h. The formulation was shown to have greater cytotoxicity relative to nedaplatin on hepatocellular carcinoma, breast cancer and ovarian cancer cell lines with IC50 values of 0.40 ± 0.08, 1.50 ± 0.12, and 0.70 ± 0.09 µg/mL, respectively. Loading nedaplatin onto CuO nanoparticles synthesized using red algae extract, greatly enhances its anticancer effect. Full article
(This article belongs to the Special Issue Tissue Engineered Biomaterials and Drug Delivery Systems)
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24 pages, 5189 KiB  
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
by Liliana-Roxana Balahura, Sorina Dinescu, Mihaela Balaș, Alexandra Cernencu, Adriana Lungu, George Mihail Vlăsceanu, Horia Iovu and Marieta Costache
Pharmaceutics 2021, 13(8), 1189; https://doi.org/10.3390/pharmaceutics13081189 - 01 Aug 2021
Cited by 15 | Viewed by 3645
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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14 pages, 9264 KiB  
Article
Bioengineered Nanoparticles Loaded-Hydrogels to Target TNF Alpha in Inflammatory Diseases
by Isabel Matos Oliveira, Diogo Castro Fernandes, Fátima Raquel Maia, Raphael Faustino Canadas, Rui Luís Reis and Joaquim Miguel Oliveira
Pharmaceutics 2021, 13(8), 1111; https://doi.org/10.3390/pharmaceutics13081111 - 21 Jul 2021
Cited by 13 | Viewed by 2774
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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13 pages, 3105 KiB  
Article
Self-Encapsulation of Biomacromolecule Drugs in Porous Microscaffolds with Aqueous Two-Phase Systems
by Jian Kang, Yunpeng Cai, Ziwei Wu, Siyi Wang and Wei-En Yuan
Pharmaceutics 2021, 13(3), 426; https://doi.org/10.3390/pharmaceutics13030426 - 22 Mar 2021
Cited by 5 | Viewed by 2163
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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18 pages, 7605 KiB  
Article
Chondrogenic Commitment of Human Bone Marrow Mesenchymal Stem Cells in a Perfused Collagen Hydrogel Functionalized with hTGF-β1-Releasing PLGA Microcarrier
by Erwin Pavel Lamparelli, Joseph Lovecchio, Maria Camilla Ciardulli, Valentina Giudice, Tina P. Dale, Carmine Selleri, Nicholas Forsyth, Emanuele Giordano, Nicola Maffulli and Giovanna Della Porta
Pharmaceutics 2021, 13(3), 399; https://doi.org/10.3390/pharmaceutics13030399 - 17 Mar 2021
Cited by 36 | Viewed by 5025
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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23 pages, 4836 KiB  
Review
Construction of Local Drug Delivery System on Titanium-Based Implants to Improve Osseointegration
by Fanying Meng, Zhifeng Yin, Xiaoxiang Ren, Zhen Geng and Jiacan Su
Pharmaceutics 2022, 14(5), 1069; https://doi.org/10.3390/pharmaceutics14051069 - 17 May 2022
Cited by 17 | Viewed by 3243
Abstract
Titanium and its alloys are the most widely applied orthopedic and dental implant materials due to their high biocompatibility, superior corrosion resistance, and outstanding mechanical properties. However, the lack of superior osseointegration remains the main obstacle to successful implantation. Previous traditional surface modification [...] Read more.
Titanium and its alloys are the most widely applied orthopedic and dental implant materials due to their high biocompatibility, superior corrosion resistance, and outstanding mechanical properties. However, the lack of superior osseointegration remains the main obstacle to successful implantation. Previous traditional surface modification methods of titanium-based implants cannot fully meet the clinical needs of osseointegration. The construction of local drug delivery systems (e.g., antimicrobial drug delivery systems, anti-bone resorption drug delivery systems, etc.) on titanium-based implants has been proved to be an effective strategy to improve osseointegration. Meanwhile, these drug delivery systems can also be combined with traditional surface modification methods, such as anodic oxidation, acid etching, surface coating technology, etc., to achieve desirable and enhanced osseointegration. In this paper, we review the research progress of different local drug delivery systems using titanium-based implants and provide a theoretical basis for further research on drug delivery systems to promote bone–implant integration in the future. Full article
(This article belongs to the Special Issue Tissue Engineered Biomaterials and Drug Delivery Systems)
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24 pages, 1510 KiB  
Review
Hydroxyapatite Nanoparticles in Drug Delivery: Physicochemistry and Applications
by Sofía Lara-Ochoa, Wendy Ortega-Lara and Carlos Enrique Guerrero-Beltrán
Pharmaceutics 2021, 13(10), 1642; https://doi.org/10.3390/pharmaceutics13101642 - 09 Oct 2021
Cited by 79 | Viewed by 5784
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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