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Advances in Polymeric Biomaterials: Drug Delivery and Tissue Engineering

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A special issue of Polymers (ISSN 2073-4360). This special issue belongs to the section "Polymer Applications".

Deadline for manuscript submissions: closed (15 October 2022) | Viewed by 28085

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Special Issue Editor

Dr. Pooya Davoodi

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Guest Editor

School of Pharmacy and Bioengineering, Keele University, Staffordshire ST5 5BG, UK
Interests: advanced biomaterials; especially hydrogel; drug delivery; additive manufacturing and 3D bioprinting
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Polymeric biomaterials have played a pivotal role in recent advances in drug delivery and tissue engineering, and in promoting the healing process in regenerative medicine. These biomaterials provide the unique features and structural flexibility that enable us to tailor their physicochemical and mechanical properties according to desired applications. Advances in our understanding of cell biology and organ tissue properties and functions have accelerated the development of sophisticated polymeric biomaterials with, for example, stimuli-responsive linkages suitable for on-demand or programmed drug delivery or tissue engineering scaffolds with biomimetic functional groups.

Besides, the development of biomanufacturing processes (e.g. 3D bioprinting, electrospinning, etc.) has provided a unique opportunity to shape natural and/or synthetic biomaterials into the desired geometry, with precise control over multiple compositions, spatial distributions, and architectural accuracy/complexity. These have also opened a new frontier in a relatively new concept of personalized medicine, where a custom-designed drug delivery device or an organ tissue implant embedded with cells can be fabricated to meet a patient’s individual health needs.

This Special Issue aims to highlight and promote recent advances in the synthesis, characterizations, and applications of innovative polymeric biomaterials in drug delivery and tissue engineering. It also covers the potential applications of such biomaterials in biofabrication, 3D bioprinting, surface bio-functionalization, and implantable devices and sensors.

Dr. Pooya Davoodi
Guest Editor

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. Polymers is an international peer-reviewed open access semimonthly 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.

Keywords

biomaterials
biopolymers
functional biomaterials
conductive biomaterials
drug/gene delivery
tissue engineering
regenerative medicine
microparticles
nanoparticles
nanomedicine
biomimetic scaffolds
extracellular matrix (ECM)
injectable polymers and hydrogels
hydrogels
polymeric implants
bio-adhesives
3D bioprinting
4D bioprinting
bio-inks
additive manufacturing
electrospinning
electrospraying
microfluidics
personalized medicine

Published Papers (8 papers)

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Research

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18 pages, 5331 KiB

Open AccessArticle

Biocompatibility Assessment of Two Commercial Bone Xenografts by In Vitro and In Vivo Methods

by Carlos Humberto Valencia-Llano, Diego López-Tenorio and Carlos David Grande-Tovar

Polymers 2022, 14(13), 2672; https://doi.org/10.3390/polym14132672 - 30 Jun 2022

Cited by 3 | Viewed by 1508

Abstract

Bone substitutes based on xenografts have been used for a long time in bone regeneration thanks to their inductive capacity for bone tissue regeneration. Some bone-based scaffolds have been modified by adding collagen and other proteins to improve their regenerative capacity and prevent migration and aggregation, especially particles. However, rejection of this graft has been reported due to protein residues caused by poor material preparation. We compared the in vitro and in vivo biological response of two commercial xenografts (InterOss^®, F1 and InterOss^® Collagen, F2) and a commercial porcine collagen membrane (InterCollagen^® Guide, F3) as a rapid degradation control. Fourier Transform Infrared Spectroscopy (FT-IR) analysis evidenced the presence of hydroxyl, orthophosphate, and carbonate groups of the xenografts and amide groups of collagen. Thermogravimetric analysis (TGA) of the xenografts demonstrated their thermal stability and the presence of a few amounts of organic material. The study by differential scanning calorimetry showed the presence of endothermic peaks typical of the dehydration of the xenografts (F1 and F2) and for the collagen membrane (F3), the beginning of structural three-dimensional protein changes. Subsequently, in vitro biocompatibility tests were carried out for the materials with Artemia salina and MTT cell viability with HeLa cells, demonstrating the high biocompatibility of the materials. Finally, in vivo biocompatibility was studied by implanting xenografts in biomodels (Wistar rats) at different periods (30, 60, and 90 days). The F1 xenograft (InterOss) remained remarkably stable throughout the experiment (90 days). F2 (InterOss Collagen) presented a separation of its apatite and collagen components at 60 days and advanced resorption at 90 days of implantation. Finally, the collagen membrane (F3) presented faster resorption since, at 90 days, only some tiny fragments of the material were evident. All the in vivo and in vitro test results demonstrated the biocompatibility of the xenografts, demonstrating the potential of these materials for tissue engineering. Full article

(This article belongs to the Special Issue Advances in Polymeric Biomaterials: Drug Delivery and Tissue Engineering)

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20 pages, 2071 KiB

Open AccessArticle

Formulation and Evaluation of Hydrophilic Polymer Based Methotrexate Patches: In Vitro and In Vivo Characterization

by Muhammad Shahid Latif, Fatemah F. Al-Harbi, Asif Nawaz, Sheikh Abdur Rashid, Arshad Farid, Mohammad Al Mohaini, Abdulkhaliq J. Alsalman, Maitham A. Al Hawaj and Yousef N. Alhashem

Polymers 2022, 14(7), 1310; https://doi.org/10.3390/polym14071310 - 24 Mar 2022

Cited by 17 | Viewed by 3686

Abstract

This study attempted to develop and evaluate controlled-release matrix-type transdermal patches with different ratios of hydrophilic polymers (sodium carboxymethylcellulose and hydroxypropyl methylcellulose) for the local delivery of methotrexate. Transdermal patches were formulated by employing a solvent casting technique using blends of sodium carboxymethylcellulose (CMC-Na) and hydroxypropylmethylcellulose (HPMC) polymers as rate-controlling agents. The F1 formulated patch served as the control formulation with a 1:1 polymer concentration. The F9 formulation served as our optimized formulation due to suitable physicochemical properties yielded through the combination of CMC-Na and HPMC (5:1). Drug excipient compatibilities (ATR-FTIR) were performed as a preformulation study. The ATR-FTIR study depicted great compatibility between the drug and the polymers. Physicochemical parameters, kinetic modeling, in vitro drug release, ex vivo drug permeation, skin drug retention, and in vivo studies were also carried out for the formulated patches. The formulated patches exhibited a clear, smooth, elastic nature with good weight uniformity, % moisture uptake, drug content, and thickness. Physicochemical characterization revealed folding endurance ranging from 62 ± 2.21 to 78 ± 1.54, tensile strength from 9.42 ± 0.52 to 12.32 ± 0.72, % swelling index from 37.16 ± 0.17 to 76.24 ± 1.37, and % drug content from 93.57 ± 5.34 to 98.19 ± 1.56. An increase in the concentration of the CMC-Na polymer (F9) resulted in increased drug release from the formulated transdermal patches. Similarly, drug permeation and retention were found to be higher in the F9 formulation compared to the other formulations (F1–F8). A drug retention analysis revealed that the F9 formulation exhibited 13.43% drug retention in the deep layers of the skin compared to other formulations (F1–F8). The stability study indicated that, during the study period of 60 days, no significant changes in the drug content and physical characteristics were found. ATR-FTIR analysis of rabbit skin samples treated with the formulated transdermal patches revealed that hydrophilic polymers mainly affect the skin proteins (ceramide and keratins). A pharmacokinetic profile revealed C_max was 1.77.38 ng/mL, T_max was 12 h, and t_1/2 was 17.3 ± 2.21. In vivo studies showed that the skin drug retention of F9 was higher compared to the drug solution. These findings reinforce that methotrexate-based patches can possibly be used for the management of psoriasis. This study can reasonably conclude that methotrexate transdermal matrix-type patches with CMC-Na and HPMC polymers at different concentrations effectively sustain drug release with prime permeation profiles and better bioavailability. Therefore, these formulated patches can be employed for the potential management of topical diseases, such as psoriasis. Full article

(This article belongs to the Special Issue Advances in Polymeric Biomaterials: Drug Delivery and Tissue Engineering)

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23 pages, 3776 KiB

Open AccessArticle

Utilization of Gelling Polymer to Formulate Nanoparticles Loaded with Epalrestat-Cyclodextrin Inclusion Complex: Formulation, Characterization, In-Silico Modelling and In-Vivo Toxicity Evaluation

by Zunaira Alvi, Muhammad Akhtar, Nisar U. Rahman, Khaled M. Hosny, Amal M. Sindi, Barkat A. Khan, Imran Nazir and Hadia Sadaquat

Polymers 2021, 13(24), 4350; https://doi.org/10.3390/polym13244350 - 12 Dec 2021

Cited by 8 | Viewed by 2521

Abstract

Epalrestat (EPL) is an aldose reductase inhibitor with poor aqueous solubility that affects its therapeutic efficacy. The research study was designed to prepare epalrestat-cyclodextrins (EPL-CDs) inclusion complexes to enhance the aqueous solubility by using beta-cyclodextrin (β-CD) and sulfobutyl ether₇ β-CD (SBE₇ β-CD). Furthermore, polymeric nanoparticles (PNPs) of EPL-CDs were developed using chitosan (CS) and sodium tripolyphosphate (sTPP). The EPL-CDs complexed formulations were then loaded into chitosan nanoparticles (CS NPs) and further characterized for different physico-chemical properties, thermal stability, drug-excipient compatibility and acute oral toxicity studies. In-silico molecular docking of cross-linker with SBE₇ β-CD was also carried out to determine the binding site of the CDs with the cross-linker. The sizes of the prepared NPs were laid in the range of 241.5–348.4 nm, with polydispersity index (PDI) ranging from 0.302–0.578. The surface morphology of the NPs was found to be non-porous, smooth, and spherical. The cumulative percentage of drug release from EPL-CDs loaded CS NPs was found to be higher (75–88%) than that of the pure drug (25%). Acute oral toxicity on animal models showed a biochemical, histological profile with no harmful impact at the cellular level. It is concluded that epalrestat-cyclodextrin chitosan nanoparticles (EPL-CDs-CS NPs) with improved solubility are safe for oral administration since no toxicity was reported on vital organs in rabbits. Full article

(This article belongs to the Special Issue Advances in Polymeric Biomaterials: Drug Delivery and Tissue Engineering)

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16 pages, 2237 KiB

Open AccessArticle

Nano Drug Delivery Platforms for Dental Application: Infection Control and TMJ Management—A Review

by Abhishek Lal, Mohammad Khursheed Alam, Naseer Ahmed, Afsheen Maqsood, Ruba K. Al-Qaisi, Deepti Shrivastava, Zainab Ali Alkhalaf, Amal Mohamed Alanazi, Hasna Rasheed Alshubrmi, Mohammed G. Sghaireen and Kumar Chandan Srivastava

Polymers 2021, 13(23), 4175; https://doi.org/10.3390/polym13234175 - 29 Nov 2021

Cited by 10 | Viewed by 3238

Abstract

The oral cavity is an intricate environment subjected to various chemical, physical, and thermal injuries. The effectiveness of the local and systemically administered drugs is limited mainly due to their toxicities and poor oral bioavailability that leads to the limited effectiveness of the drugs in the target tissues. To address these issues, nanoparticle drug delivery systems based on metals, liposomes, polymeric particles, and core shells have been developed in recent years. Nano drug delivery systems have applications in the treatment of patients suffering from temporomandibular joint disorders such as preventing degeneration of cartilage in patients suffering from rheumatoid arthritis and osteoarthritis and alleviating the pain along with it. The antibacterial dental applications of nano-drug delivery systems such as silver and copper-based nanoparticles include these agents used to arrest dental caries, multiple steps in root canal treatment, and patients suffering from periodontitis. Nanoparticles have been used in adjunct with antifungals to treat oral fungal infections such as candida albicans in denture wearers. Acyclovir being the most commonly used antiviral has been used in combination with nanoparticles against an array of viral infections such as the herpes simplex virus. Nanoparticles based combination agents offer more favorable drug release in a controlled manner along with efficient delivery at the site of action. This review presents an updated overview of the recently developed nanoparticles delivery systems for the management of temporomandibular joint disorders along with the treatment of different oral infections. Full article

(This article belongs to the Special Issue Advances in Polymeric Biomaterials: Drug Delivery and Tissue Engineering)

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15 pages, 33337 KiB

Open AccessArticle

Cefotaxime Loaded Polycaprolactone Based Polymeric Nanoparticles with Antifouling Properties for In-Vitro Drug Release Applications

by Sana Javaid, Nasir M. Ahmad, Azhar Mahmood, Habib Nasir, Mudassir Iqbal, Naveed Ahmad and Sundus Irshad

Polymers 2021, 13(13), 2180; https://doi.org/10.3390/polym13132180 - 30 Jun 2021

Cited by 14 | Viewed by 2963

Abstract

The objective of the present study was to achieve the successful encapsulation of a therapeutic agent to achieve antifouling functionality regarding biomedical applications. Considering nanotechnology, drug-loaded polycaprolactone (PCL)-based nanoparticles were prepared using a nano-precipitation technique by optimizing various process parameters. The resultant nano-formulations were investigated for in vitro drug release and antifouling applications. The prepared particles were characterized in terms of surface morphology and surface properties. Optimized blank and drug-loaded nanoparticles had an average size of 200 nm and 216 nm, respectively, with associated charges of −16.8 mV and −11.2 mV. Studies of the in vitro release of drug were carried out, which showed sustained release at two different pH, 5.5 and 7.4 Antifouling activity was observed against two bacterial strains, Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. The zone of inhibition of the optimized polymeric drug-loaded nanoparticle F-25 against both strains were compared with the pure drug. The gradual pH-responsive release of antibiotics from the biodegradable polymeric nanoparticles could significantly increase the efficiency and pharmacokinetics of the drug as compared to the pure drug. The acquired data significantly noted that the resultant nano-encapsulation of antifouling functionality could be a promising candidate for topical drug delivery systems and skin applications. Full article

(This article belongs to the Special Issue Advances in Polymeric Biomaterials: Drug Delivery and Tissue Engineering)

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14 pages, 1765 KiB

Open AccessArticle

Preparation and Drug Release Properties of a Thermo Sensitive GA Hydrogel

by Jiufang Duan, Yirong Huang, Shiyu Zong and Jianxin Jiang

Polymers 2021, 13(1), 119; https://doi.org/10.3390/polym13010119 - 30 Dec 2020

Cited by 19 | Viewed by 3007

Abstract

A high-strength galactomannan (GA)-based hydrogel with thermal response and pH response is introduced in this paper. GA, N-isopropylacrylamide (NIPAM), N-[3-dimethylamino)propyl]methylacrylamide (DMAPMA), and montmorillonite were used to form hydrogels through a simple mixed static system. Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), and scanning electron microscopy (SEM) were used to characterize the structure and properties of the hydrogels. The compressive strength of the the hydrogel increased from 23.9 to 105.61 kPa with the increase of GA dosage from 0 to 1.5 wt%. When the NIPAM content in the monomer increased from 75% to 95%, the lower critical solution temperature (LCST) of the hydrogel changed from 36.5 to 45.8 °C. When the monomer content was higher than 10wt%, the swelling kinetics of the sample changed from the second-order equation to the first-order equation. With the increase of the proportion of NIPAM monomer, the release rate of bovine serum album in the early stage was faster, and the cumulative release rate was close to 100%.The release rate of bovine serum albumin at 37 °C was higher than that at 25 °C. The release rate of the hydrogel containing bovine serum albumin was the fastest under the condition of pH 7.4, followed by those at pH 6.6 and pH 5.0. The results showed that this thermal-responsive hydrogel has potential applications as a drug carrier for colon delivery. Full article

(This article belongs to the Special Issue Advances in Polymeric Biomaterials: Drug Delivery and Tissue Engineering)

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Review

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17 pages, 2862 KiB

Open AccessReview

Photo-Induced Drug Release from Polymeric Micelles and Liposomes: Phototriggering Mechanisms in Drug Delivery Systems

by Najla M. Salkho, Nahid S. Awad, William G. Pitt and Ghaleb A. Husseini

Polymers 2022, 14(7), 1286; https://doi.org/10.3390/polym14071286 - 23 Mar 2022

Cited by 21 | Viewed by 4374

Abstract

Chemotherapeutic drugs are highly effective in treating cancer. However, the side effects associated with this treatment lower the quality of life of cancer patients. Smart nanocarriers are able to encapsulate these drugs to deliver them to tumors while reducing their contact with the healthy cells and the subsequent side effects. Upon reaching their target, the release of the encapsulated drugs should be carefully controlled to achieve therapeutic levels at the required time. Light is one of the promising triggering mechanisms used as external stimuli to trigger drug release from the light-responsive nanocarriers. Photo-induced drug release can be achieved at a wide range of wavelengths: UV, visible, and NIR depending on many factors. In this review, photo-induced release mechanisms were summarized, focusing on liposomes and micelles. In general, light-triggering mechanisms are based on one of the following: changing the hydrophobicity of a nanocarrier constituent(s) to make it more soluble, introducing local defects within a nanocarrier (by conformational transformation or photo-cleavage of its lipids/polymers chains) to make it more porous or concentrating heat for thermo-sensitive nanocarriers to release their payload. Several research studies were also presented to explore the potentials and limitations of this promising drug release triggering mechanism. Full article

(This article belongs to the Special Issue Advances in Polymeric Biomaterials: Drug Delivery and Tissue Engineering)

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35 pages, 7391 KiB

Open AccessReview

Advanced Hydrogels for Cartilage Tissue Engineering: Recent Progress and Future Directions

by Mahshid Hafezi, Saied Nouri Khorasani, Mohadeseh Zare, Rasoul Esmaeely Neisiany and Pooya Davoodi

Polymers 2021, 13(23), 4199; https://doi.org/10.3390/polym13234199 - 30 Nov 2021

Cited by 38 | Viewed by 5482

Abstract

Cartilage is a tension- and load-bearing tissue and has a limited capacity for intrinsic self-healing. While microfracture and arthroplasty are the conventional methods for cartilage repair, these methods are unable to completely heal the damaged tissue. The need to overcome the restrictions of these therapies for cartilage regeneration has expanded the field of cartilage tissue engineering (CTE), in which novel engineering and biological approaches are introduced to accelerate the development of new biomimetic cartilage to replace the injured tissue. Until now, a wide range of hydrogels and cell sources have been employed for CTE to either recapitulate microenvironmental cues during a new tissue growth or to compel the recovery of cartilaginous structures via manipulating biochemical and biomechanical properties of the original tissue. Towards modifying current cartilage treatments, advanced hydrogels have been designed and synthesized in recent years to improve network crosslinking and self-recovery of implanted scaffolds after damage in vivo. This review focused on the recent advances in CTE, especially self-healing hydrogels. The article firstly presents the cartilage tissue, its defects, and treatments. Subsequently, introduces CTE and summarizes the polymeric hydrogels and their advances. Furthermore, characterizations, the advantages, and disadvantages of advanced hydrogels such as multi-materials, IPNs, nanomaterials, and supramolecular are discussed. Afterward, the self-healing hydrogels in CTE, mechanisms, and the physical and chemical methods for the synthesis of such hydrogels for improving the reformation of CTE are introduced. The article then briefly describes the fabrication methods in CTE. Finally, this review presents a conclusion of prevalent challenges and future outlooks for self-healing hydrogels in CTE applications. Full article

(This article belongs to the Special Issue Advances in Polymeric Biomaterials: Drug Delivery and Tissue Engineering)

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