Submit to Molecules Review for Molecules Propose a Special Issue

Journal Browser

► Journal Browser

Inventive Biomaterials for Tissue Engineering and Drug Delivery Applications

Special Issue Editors
Special Issue Information
Keywords
Published Papers

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Materials Chemistry".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 18695

Share This Special Issue

Special Issue Editor

Dr. Muthukumar Thangavelu

E-Mail Website
Guest Editor

Department of Physiology, Chonbuk National University, Deokjin-gu, Jeonju 561-756, Republic of Korea
Interests: biomaterials; hydrogels; scaffolds; wound healing; bone tissue engineering; bone regeneration; drug delivery; tissue engineering; nanomaterial; polymer degardation

Special Issue Information

Dear Colleagues,

Biomaterial plays a central element for tissue engineering (TE). TE is a promising and advancing field that plays a major role in restoring of damaged tissue by merging cells with biomaterials that can act as a template for the regeneration of tissues and organs. TE is a highly multidisciplinary field that includes different areas, including material science, clinical medicine, mechanical engineering, genetics, drug delivery, cell culture, and other disciplines related to life sciences and engineering. The TE field is mainly based on the use of biomimetic materials (in different forms such as scaffolds, hydrogels etc.) that provide both suitable environment for the development of new tissue and base for cell adhesion, proliferation, and new tissue formation. In recent years, even the natural and synthetic biomaterials have become very important basics for the TE and regenerative medicine strategies. Emerging fields of 3D bioprinting technology use biomaterials in a precise spatial arrangement way to fabricate 3D cellularized constructs for invitro models, therapeutics, and drug delivery applications.

The goal of this Special Issue is to cover current advances and promising developments in the design and development of biomaterials for tissue engineering and organ development, including biomaterials, hydrogels, bioactive materials, composites, biodegradable polymers, nanofibers, and microfibers. Biomaterials for in vitro and in vivo studies, biocompatibility, drug delivery, wound healing, bone healing, vascular tissue engineering, organs, and other products for the clinical application in the restoration of damaged tissue or organs will be discussed.

Dr. Muthukumar Thangavelu
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. Molecules 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

biomaterial
scaffold
hydrogels
biofabrication
cell culture
tissue engineering
drug delivery
biocompatibility
organ development

Published Papers (9 papers)

Download All Papers

Research

Jump to: Review

12 pages, 2572 KiB

Open AccessArticle

Evaluation of Silk Fibroin/Gellan Gum Hydrogels with Controlled Molecular Weight through Silk Fibroin Hydrolysis for Tissue Engineering Application

by Sunjae Park, Soo-In Kim, Joo-Hee Choi, Se-Eun Kim, Seung-Ho Choe, Youngjun Son, Tae-woong Kang, Jeong-Eun Song and Gilson Khang

Molecules 2023, 28(13), 5222; https://doi.org/10.3390/molecules28135222 - 05 Jul 2023

Cited by 3 | Viewed by 977

Abstract

Hydrogel is a versatile material that can be manipulated to achieve the desired physicochemical properties, such as stiffness, pore size, and viscoelasticity. Traditionally, these properties have been controlled through parameters such as concentration and pH adjustments. In this study, we focused on exploring the potential of hydrolyzed silk fibroin (HSF) as a molecular weight-modulating agent to control the physicochemical properties of double-composite hydrogels. We developed a synergistic dual-crosslinked hydrogel by combining ionically crosslinked silk fibroin with gellan gum (GG). The hydrolysis of silk fibroin not only enhanced its hydrophilicity but also enabled adjustments in its mechanical properties, including the pore size, initial modulus elasticity, and relaxation time. Moreover, biocompatibility assessments based on cell viability tests confirmed the potential of these hydrogels as biocompatible materials. By highlighting the significance of developing an HSF/GG dual-crosslinked hydrogel, this study contributes to the advancement of novel double-composite hydrogels with remarkable biocompatibility. Overall, our findings demonstrate the capability of controlling the mechanical properties of hydrogels through molecular weight modulation via hydrolysis and highlight the development of a biocompatible HSF/GG dual-crosslinked hydrogel with potential biomedical applications. Full article

(This article belongs to the Special Issue Inventive Biomaterials for Tissue Engineering and Drug Delivery Applications)

► Show Figures

Figure 1

12 pages, 2678 KiB

Open AccessFeature PaperArticle

Functionalization of Framboidal Phenylboronic Acid-Containing Nanoparticles via Aqueous Suzuki–Miyaura Coupling Reactions

by André J. van der Vlies and Urara Hasegawa

Molecules 2023, 28(8), 3602; https://doi.org/10.3390/molecules28083602 - 20 Apr 2023

Viewed by 1371

Abstract

Polymeric nanoparticles with reactive functional groups are an attractive platform for drug carriers that can be conjugated with drugs through a cleavable covalent linkage. Since the required functional groups vary depending on the drug molecule, there is a need for development of a novel post-modification method to introduce different functional groups to polymeric nanoparticles. We recently reported phenylboronic acid (PBA)-containing nanoparticles (BNP) with a unique framboidal morphology created via one-step aqueous dispersion polymerization. Since BNPs have high surface area due to their framboidal morphology and contain a high density of PBA groups, these particles can be used as nanocarriers for drugs that can bind to PBA groups such as curcumin and a catechol-bearing carbon monoxide donor. To further explore the potential of BNPs, in this article we report a novel strategy to introduce different functional groups to BNPs via the palladium-catalyzed Suzuki–Miyaura cross-coupling reaction between the PBA groups and iodo- and bromo-coupling partners. We developed a new catalytic system that efficiently catalyzes Suzuki–Miyaura reactions in water without the need for an organic solvent, as confirmed by NMR. Using this catalyst system, we show that BNPs can be functionalized with carboxylic acids, aldehyde, and hydrazide groups while keeping their original framboidal morphology as confirmed via IR, alizarin red assay, and TEM. Furthermore, the potential of the functionalized BNP in drug delivery applications was demonstrated by conjugating the hydrogen sulfide (H₂S)-releasing compound anethole dithiolone to carboxylic acid-functionalized BNPs and show their H₂S-releasing capability in cell lysate. Full article

(This article belongs to the Special Issue Inventive Biomaterials for Tissue Engineering and Drug Delivery Applications)

► Show Figures

Figure 1

17 pages, 3543 KiB

Open AccessArticle

Chitosan Encapsulated Meloxicam Nanoparticles for Sustained Drug Delivery Applications: Preparation, Characterization, and Pharmacokinetics in Wistar Rats

by Muralidhar Yegireddy, Prakash Nadoor, Suguna Rao, Pavithra Balekatte Hanumanthu, Rashmi Rajashekaraiah, Santhosh Chickankandahalli Ramachandrappa, Girish Mallikarjun Halemani, Sravanthi Mannem, Tollamadugu Naga Venkata Krishna Vara Prasad and Sunilchandra Ubaradka

Molecules 2022, 27(21), 7312; https://doi.org/10.3390/molecules27217312 - 27 Oct 2022

Cited by 3 | Viewed by 1636

Abstract

Meloxicam (MLX) is currently used in the therapeutic management of both acute and chronic inflammatory disorders such as pain, injuries, osteoarthritis, and rheumatoid arthritis in both humans and animals. Gastrointestinal toxicity and occasional renal toxicity were observed in patients taking it for a long-term period. Meloxicam’s late attainment of peak plasma concentration results in a slow onset of action. The goal of the current study was to prepare and characterize chitosan encapsulated meloxicam nanoparticles (CEMNPs) with high bioavailability and less gastro intestinal toxicity in order to prevent such issues. The size of the prepared CEMNPs was approximately 110–220 nm with a zetapotential of +39.9 mV and polydispersity index of 0.268, suggesting that they were uniformly dispersed nanoparticles. The FTIR and UV-Vis spectroscopy have confirmed the presence of MLX in the prepared CEMNPs. The pharmacokinetics have been studied with three groups of male Wistar rats receiving either of the treatments, viz., 4 mg·kg⁻¹ of MLX and 1 or 4 mg·kg⁻¹ of CEMNPs. Plasma samples were collected until 48 h post administration, and concentrations of MLX were quantified by using reverse (C₁₈) phase HPLC. Non-compartmental analysis was applied to determine pharmacokinetic variables. Upon oral administration, the maximum concentration (C_max) was reached in 4 h for CEMNPs and 6 h for MLX. The mean area under the plasma MLX concentration-time curve from ‘zero’ to infinity (AUC_0–∞), half-life (t_1/2β), and mean resident time (MRT) of 1 mg·kg⁻¹ of CEMNPs was 1.4-, 2-, and 1.8-fold greater than 4 mg·kg⁻¹ of MLX. The prepared CEMNPs demonstrated quicker absorption and prolonged release along with a significant improvement in the bioavailability of MLX, paving a prospective path for the development of drugs with enhanced bioavailability with less side effects. Full article

(This article belongs to the Special Issue Inventive Biomaterials for Tissue Engineering and Drug Delivery Applications)

► Show Figures

Figure 1

24 pages, 5996 KiB

Open AccessArticle

Evaluation of Human Osteoblasts on NIPS Micro-Patterned PCL Carriers Containing Nanohydroxyapatite and Reduced Graphene Oxide Using PSµM

by Burcu Tüzün-Antepli, Şükran Şeker, Ayşe Eser Elçin, Gilson Khang and Yaşar Murat Elçin

Molecules 2022, 27(20), 7091; https://doi.org/10.3390/molecules27207091 - 20 Oct 2022

Cited by 4 | Viewed by 1507

Abstract

The content and surface topology of tissue engineering scaffolds are two important parameters in regulating the cell behavior. In this study, a phase separation micromolding (PSµM) method was implemented to develop micro-groove-imprinted poly(ε-caprolactone) (PCL)–nano hydroxyapatite (nHAp)–reduced graphene oxide (rGO) ternary blend constructs. Physical and chemical characterizations of cell-devoid constructs were performed by FTIR, XRD, TGA, DSC, porosity, swelling, wettability analysis, tensile and compression mechanical tests. The in vitro biological performance of human osteoblasts cultured on micro-patterned blend constructs was evaluated by MTT and alamarBlue viability assays. The findings revealed that nHAp and rGO significantly promote cell viability and proliferation, while the micro-pattern determines the direction of cell migration. Alkaline phosphatase and Ca²⁺ analyses were carried out to determine the osteogenic properties of cell-laden constructs. This study describes a simple method to generate topologically modified ternary blend PCL/nHAp/rGO constructs using the PSµM method, which contributes to cell proliferation and migration, which is particularly important in regenerative medicine. Full article

(This article belongs to the Special Issue Inventive Biomaterials for Tissue Engineering and Drug Delivery Applications)

► Show Figures

Graphical abstract

16 pages, 2488 KiB

Open AccessArticle

Honey-Propolis-Engineered Collagen Peptides as Promising Wound-Healing Matrix in Mouse Model

by Hairul-Islam Mohamed Ibrahim, Muthukumar Thangavelu and Ashraf Khalifa

Molecules 2022, 27(20), 7090; https://doi.org/10.3390/molecules27207090 - 20 Oct 2022

Cited by 5 | Viewed by 2652

Abstract

In this study, collagen hydrolysates (CHDs) were fabricated with honey-propolis wax (HPW), structurally modified as a sponge matrix, and experimentalized on wound healing in a mouse model. The scaffold was characterized by means of in vitro enzymatic degradation; in vitro HPW release; and in vivo wound-healing mouse model, wound-healing-specific RNA, transcripts, and protein markers. The functional activity of the HPW extracted from raw propolis was determined using total flavonoids, antioxidant scavenging assays, and anti-hemolytic principles. The results indicated that HPW had a high flavonoid content (20 μg/mL of wax) and antioxidant activities. The effective concentration (EC50) of HPW was estimated (28 mg/mL) and was then used in the subsequent in vivo experiments. Additionally, the dopped mixture of CHDs and HPW substantially enhanced the wound-healing process and regulated wound biochemical markers such as hexoseamine and melondialdehyde. CHDs- HPW upregulated the expression of growth factors including vascular endothelial growth factor (VEGF) (2.3-fold), fibroblast growth factor (FGF) and epidermal growth factor (EGF) (1.7-fold), and transforming growth factor-beta (TGF-β) (3.1-fold), indicating their potential capacity to perform wound re-epithelialization and the loading of ground tissue. Pro-inflammatory markers IL-1 β (51 pg/mL) and TNF-α (220 pg/mL) were significantly reduced in the CHD-HPW-treated wound. These interesting results were further confirmed using mRNA and protein growth factors from the wound, which enhanced the load of collagen-I in the wound site. In conclusion, CHDs-HPW exhibited a significant reduction in inflammation and inflammatory markers and helped to obtain a faster wound-healing process in a mouse model. The newly engineered biosponge could be developed as a promising therapeutic approach for the regeneration and repair of damaged human skin in the future. Full article

(This article belongs to the Special Issue Inventive Biomaterials for Tissue Engineering and Drug Delivery Applications)

► Show Figures

Graphical abstract

11 pages, 4048 KiB

Open AccessArticle

Microneedles: One-Plane Bevel-Tipped Fabrication by 3D-Printing Processes

by Isabella Villota, Paulo C. Calvo, Oscar I. Campo and Faruk Fonthal

Molecules 2022, 27(19), 6634; https://doi.org/10.3390/molecules27196634 - 06 Oct 2022

Cited by 2 | Viewed by 1611

Abstract

This article presents microneedles analyses where the design parameters studied included length and inner and outer diameter ranges. A mathematical model was also used to generalize outer and inner diameter ratios in the obtained ranges. Following this, the range of inner and outer diameters was completed by mechanical simulations, ranging from 30 μm to 134 μm as the inner diameter range and 208 μm to 250 μm as the outer diameter range. With these ranges, a mathematical model was made using fourth-order polynomial regressions with a correlation of 0.9993, ensuring a safety factor of four in which von Misses forces of the microneedle are around 17.931 MPa; the ANSYS software was used to analyze the mechanical behavior of the microneedles. In addition, the microneedle concept was made by 3D printing using a bio-compatible resin of class 1. The features presented by the microneedle designed in this study make it a promising option for implementation in a transdermal drug-delivery device. Full article

(This article belongs to the Special Issue Inventive Biomaterials for Tissue Engineering and Drug Delivery Applications)

► Show Figures

Figure 1

15 pages, 3363 KiB

Open AccessArticle

Allogeneic Bone Impregnated with Biodegradable Depot Delivery Systems for the Local Treatment of Joint Replacement Infections: An In Vitro Study

by Libor Prokes, Eva Snejdrova, Tomas Soukup, Jana Malakova, Vladislav Frolov, Jan Loskot, Rudolf Andrys and Tomas Kucera

Molecules 2022, 27(19), 6487; https://doi.org/10.3390/molecules27196487 - 01 Oct 2022

Cited by 2 | Viewed by 1233

Abstract

Although progress is evident in the effective treatment of joint replacement-related infections, it still remains a serious issue in orthopedics. As an example, the local application of antibiotics-impregnated bone grafts supplies the high drug levels without systemic side effects. However, antibiotics in the powder or solution form could be a risk for local toxicity and do not allow sustained drug release. The present study evaluated the use of an antibiotic gel, a water-in-oil emulsion, and a PLGA microparticulate solid dispersion as depot delivery systems impregnating bone grafts for the treatment of joint replacement-related infections. The results of rheological and bioadhesive tests revealed the suitability of these formulations for the impregnation of bone grafts. Moreover, no negative effect on proliferation and viability of bone marrow mesenchymal stem cells was detected. An ex vivo dissolution test of vancomycin hydrochloride and gentamicin sulphate from the impregnated bone grafts showed a reduced burst and prolonged drug release. The PLGA-based formulation proved to be particularly promising, as one-day burst release drugs was only 15% followed with sustained antibiotics release with zero-order kinetics. The results of this study will be the basis for the development of a new product in the Tissue Section of the University Hospital for the treatment of bone defects and infections of joint replacements. Full article

(This article belongs to the Special Issue Inventive Biomaterials for Tissue Engineering and Drug Delivery Applications)

► Show Figures

Figure 1

17 pages, 4547 KiB

Open AccessArticle

Fabrication and Evaluation of Gellan Gum/Hyaluronic Acid Hydrogel for Retinal Tissue Engineering Biomaterial and the Influence of Substrate Stress Relaxation on Retinal Pigment Epithelial Cells

by Jina Youn, Joo Hee Choi, Sumi Lee, Wonchan Lee, Seong Won Lee, Wooyoup Kim, Youngeun Song, Nomin-Erdene Tumursukh, Jeong Eun Song and Gilson Khang

Molecules 2022, 27(17), 5512; https://doi.org/10.3390/molecules27175512 - 27 Aug 2022

Cited by 7 | Viewed by 2006

Abstract

Cell therapies for age-related macular degeneration (AMD) treatment have been developed by integrating hydrogel-based biomaterials. Until now, cell activity has been observed only in terms of the modulus of the hydrogel. In addition, cell behavior has only been observed in the 2D environment of the hydrogel and the 3D matrix. As time-dependent stress relaxation is considered a significant mechanical cue for the control of cellular activities, it is important to optimize hydrogels for retinal tissue engineering (TE) by applying this viewpoint. Herein, a gellan Gum (GG)/Hyaluronic acid (HA) hydrogel was fabricated using a facile physical crosslinking method. The physicochemical and mechanical properties were controlled by forming a different composition of GG and HA. The characterization was performed by conducting a mass swelling study, a sol fraction study, a weight loss test, a viscosity test, an injection force study, a compression test, and a stress relaxation analysis. The biological activity of the cells encapsulated in 3D constructs was evaluated by conducting a morphological study, a proliferation test, a live/dead analysis, histology, immunofluorescence staining, and a gene expression study to determine the most appropriate material for retinal TE biomaterial. Hydrogels with moderate amounts of HA showed improved physicochemical and mechanical properties suitable for injection into the retina. Moreover, the time-dependent stress relaxation property of the GG/HA hydrogel was enhanced when the appropriate amount of HA was loaded. In addition, the cellular compatibility of the GG/HA hydrogel in in vitro experiments was significantly improved in the fast-relaxing hydrogel. Overall, these results demonstrate the remarkable potential of GG/HA hydrogel as an injectable hydrogel for retinal TE and the importance of the stress relaxation property when designing retinal TE hydrogels. Therefore, we believe that GG/HA hydrogel is a prospective candidate for retinal TE biomaterial. Full article

(This article belongs to the Special Issue Inventive Biomaterials for Tissue Engineering and Drug Delivery Applications)

► Show Figures

Figure 1

Review

Jump to: Research

30 pages, 2173 KiB

Open AccessReview

Exosomes as New Generation Vehicles for Drug Delivery: Biomedical Applications and Future Perspectives

by Amarjitsing Rajput, Akansh Varshney, Rashi Bajaj and Varsha Pokharkar

Molecules 2022, 27(21), 7289; https://doi.org/10.3390/molecules27217289 - 27 Oct 2022

Cited by 29 | Viewed by 4458

Abstract

Currently, particular interest among the scientific community is focused on exploring the use of exosomes for several pharmaceutical and biomedical applications. This is due to the identification of the role of exosomes as an excellent intercellular communicator by delivering the requisite cargo comprising of functional proteins, metabolites and nucleic acids. Exosomes are the smallest extracellular vesicles (EV) with sizes ranging from 30–100 nm and are derived from endosomes. Exosomes have similar surface morphology to cells and act as a signal transduction channel between cells. They encompass different biomolecules, such as proteins, nucleic acids and lipids, thus rendering them naturally as an attractive drug delivery vehicle. Like the other advanced drug delivery systems, such as polymeric nanoparticles and liposomes to encapsulate drug substances, exosomes also gained much attention in enhancing therapeutic activity. Exosomes present many advantages, such as compatibility with living tissues, low toxicity, extended blood circulation, capability to pass contents from one cell to another, non-immunogenic and special targeting of various cells, making them an excellent therapeutic carrier. Exosome-based molecules for drug delivery are still in the early stages of research and clinical trials. The problems and clinical transition issues related to exosome-based drugs need to be overcome using advanced tools for better understanding and systemic evaluation of exosomes. In this current review, we summarize the most up-to-date knowledge about the complex biological journey of exosomes from biogenesis and secretion, isolation techniques, characterization, loading methods, pharmaceutical and therapeutic applications, challenges and future perspectives of exosomes. Full article

(This article belongs to the Special Issue Inventive Biomaterials for Tissue Engineering and Drug Delivery Applications)

► Show Figures