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Modification of Hydrogels and Their Applications in Biomedical Engineering

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A special issue of Gels (ISSN 2310-2861). This special issue belongs to the section "Gel Applications".

Deadline for manuscript submissions: closed (10 January 2023) | Viewed by 40513

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Special Issue Editors

Prof. Dr. Yanen Wang

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Guest Editor

Department of Indurstry and Engineering, School of Mechanical Engineering, Northwestern Polytechnical University, Xi’an 710072, China
Interests: biofabrication; tissue engineering; additive manufacturing; hydrogels; biomaterials; modification
Special Issues, Collections and Topics in MDPI journals

Dr. Qinghua Wei

E-Mail Website
Guest Editor

School of Mechanical Engineering, Northwestern Polytechanical University, Xi’an 710072, China
Interests: bioprinting; bioscaffold; biomaterials; polymeric hydrogels; molecular simulation
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

It is widely known that hydrogels are hydrophilic polymer networks that represent an important class of biomaterials in biotechnology and medicine due to their excellent biocompatibility with minimal inflammatory responses and tissue damage. Currently, different hydrogels have been widely used as bioscaffolds to mimic the structure and properties of tissues. These structures are able to provide a synthetic extracellular matrix to support living cells during and after the fabricating process of tissue scaffolds. Furthermore, in combination with the proliferation and differentiation techniques of stem cells, living tissues and organs are expected to be achieved, and many encouraging achievements have now been accomplished.

However, single-component hydrogels usually do not meet the basic requirements of tissue engineering. The synthetic polymer hydrogels have excellent mechanical properties, but their biological properties are often poor, which is not conducive to the adhesion and growth of cells. The natural polymers have unique biological properties, but their mechanical properties are often unsatisfactory. To promote the application of hydrogels in the biomedical field, improving the properties (biochemical, mechanical, biological, processable properties, etc.) of hydrogels is necessary.

This Special Issue focuses on the modification of hydrogels and their properties for different biomedical applications. Relevant topics include, but are not limited to, theoretical and experimental investigations, mechanical properties, biological properties, thermal performance, structural characteristics, forming processes, and tissue formation.

Prof. Dr. Yanen Wang
Dr. Qinghua Wei
Guest Editors

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Keywords

modification
hydrogel
biomaterials
bioscaffold
tissue engineering
drug delivery
composite materials

Published Papers (13 papers)

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Editorial

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3 pages, 204 KiB

Open AccessEditorial

Editorial on the Special Issue “Modification of Hydrogels and Their Applications in Biomedical Engineering”

by Yanen Wang and Qinghua Wei

Gels 2023, 9(4), 263; https://doi.org/10.3390/gels9040263 - 23 Mar 2023

Cited by 2 | Viewed by 819

Abstract

Hydrogels and hydrophilic polymer networks play an important role in biomedical engineering due to their good biocompatibility, biodegradability, hydrophilicity, and mechanical properties, similarly to some soft tissues [...] Full article

(This article belongs to the Special Issue Modification of Hydrogels and Their Applications in Biomedical Engineering)

Research

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15 pages, 6223 KiB

Open AccessArticle

Enhancing Conductivity and Self-Healing Properties of PVA/GEL/OSA Composite Hydrogels by GO/SWNTs for Electronic Skin

by Xiaohu Chen, Haonan Zhang, Jiashu Cui, Yanen Wang, Mingyang Li, Juan Zhang, Changgeng Wang, Zhisheng Liu and Qinghua Wei

Gels 2023, 9(2), 155; https://doi.org/10.3390/gels9020155 - 15 Feb 2023

Cited by 3 | Viewed by 1662

Abstract

The use of flexible, self-healing conductive hydrogels as a type of typical electronic skin with the function of transmitting sensory signals has attracted wide attention in the field of biomaterials. In this study, composite hydrogels based on polyvinyl alcohol (PVA), gelatin (GEL), oxidized sodium alginate (OSA), graphene oxide (GO), and single-walled carbon nanotubes (SWNTs) were successfully prepared. The hydrogen and imine bonding of the composite hydrogels gives them excellent self-healing properties. Their self-healing properties restore 68% of their breaking strength and over 95% of their electrical conductivity. The addition of GO and SWNTs enables the PGO-GS hydrogels to achieve a compressive modulus and conductivity of 42.2 kPa and 29.6 mS/m, which is 8.2 times and 1.5 times that of pure PGO, respectively. Furthermore, the PGO-GS hydrogels can produce profound feedback signals in response to deformation caused by external forces and human movements such as finger flexion and speech. In addition, the PGO-GS hydrogels exhibit superior biocompatibility compared to PGO. All of these results indicate that the PGO-GS hydrogels have great potential with respect to future applications in the field of electronic skin. Full article

(This article belongs to the Special Issue Modification of Hydrogels and Their Applications in Biomedical Engineering)

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14 pages, 36686 KiB

Open AccessArticle

Antibacterial Hydrogel Sheet Dressings Composed of Poly(vinyl alcohol) and Silver Nanoparticles by Electron Beam Irradiation

by Rattanakorn Chiangnoon, Pennapa Karawak, Jarurattana Eamsiri, Sasikarn Nuchdang, Nuatawan Thamrongsiripak, Naruemon Neramitmansook, Siwanut Pummarin, Pimchanok Pimton, Kewalee Nilgumhang and Pimpon Uttayarat

Gels 2023, 9(2), 80; https://doi.org/10.3390/gels9020080 - 18 Jan 2023

Cited by 6 | Viewed by 1903 | Correction

Abstract

Advanced wound dressings that can deliver potent antibacterial action are still much in need, especially for treating wound infections caused by drug-resistant bacteria. In this research, we utilized electron beam (EB) irradiation to develop antibacterial hydrogel sheet dressings from poly(vinyl alcohol) (PVA) and silver nanoparticles (AgNPs) in a two-step processing and evaluated their bactericidal efficacy, as well as the AgNP release. The effect of the irradiation dose on the swelling, gel fraction, network parameters, and mechanical properties of the hydrogels was first determined to establish the optimal doses for the two-step processing. The prototypic hydrogel sheets were then formed in the first EB irradiation and served as a matrix for the AgNP synthesis by the reduction of the silver nitrate precursors during the second EB irradiation. The diffusion assay showed that the minimal inhibition concentration (MIC) of the AgNP-load hydrogels was 0.25 and 0.5 mg/cm² against Escherichia coli and Staphylococcus aureus, respectively. At these MIC levels, the released AgNPs increased sharply before reaching the maximum, ~950 and 1800 ppb, at 24 h as analyzed by atomic absorption. Therefore, we successfully demonstrated that this two-step processing by EB irradiation provides a convenient platform to fabricate AgNP-loaded hydrogel dressings that can be further developed for wound healing. Full article

(This article belongs to the Special Issue Modification of Hydrogels and Their Applications in Biomedical Engineering)

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24 pages, 31212 KiB

Open AccessArticle

Antioxidant, Anti-Inflammatory and Attenuating Intracellular Reactive Oxygen Species Activities of Nicotiana tabacum var. Virginia Leaf Extract Phytosomes and Shape Memory Gel Formulation

by Chuda Chittasupho, Kunyakorn Chaobankrang, Araya Sarawungkad, Weerasak Samee, Sudarshan Singh, Kirachuda Hemsuwimon, Siriporn Okonogi, Kantaporn Kheawfu, Kanokwan Kiattisin and Wantida Chaiyana

Gels 2023, 9(2), 78; https://doi.org/10.3390/gels9020078 - 18 Jan 2023

Cited by 17 | Viewed by 2035

Abstract

Oxidative stress is one of the major causes of skin aging. In this study, the shape memory gels containing phytosomes were developed as a delivery system for Nicotiana tabacum var. Virginia fresh (VFL) and dry (VDL) leaf extracts. The extracts were loaded in the phytosomes by a solvent displacement method. The physical and chemical characteristics and stability of phytosomes were evaluated by dynamic light scattering and phytochemistry, respectively. The in vitro antioxidant activity and intracellular reactive oxygen species reduction of phytosomes and/or extracts were investigated by the DPPH and ABTS radical scavenging assays, FRAP assay, and DCFH-DA fluorescent probe. The cytotoxicity and anti-inflammatory activity of VDL and VFL phytosomes were studied by an MTT and a nitric oxide assay, respectively. Here, we first reported the total phenolic content in the dry leaf extract of N. tabacum var. Virginia was significantly greater than that of the fresh leaf extract. The HPLC analysis results revealed that VDL and VFL extracts contained 4.94 ± 0.04 and 3.13 ± 0.01 µg/mL of chlorogenic acid and 0.89 ± 0.00 and 0.24 ± 0.00 µg/mL of rutin, respectively. The phytosomes of the VDL and VFL extracts displayed stable size, polydispersity index, zeta potential values, and good chemical stability. VDL and VDL phytosomes showed higher phenolic and flavonoid contents which showed stronger DPPH and ABTS radical scavenging effects and reduced the intracellular ROS. The results suggested that the phenolic compounds are the main factor in their antioxidant activity. Both VDL and VFL phytosomes inhibited nitric oxide production induced by LPS, suggesting the anti-inflammatory activity of the phytosomes. The shape memory gel containing VDL and VFL phytosomes had good physical stability in terms of pH and viscosity. The VDL and VFL phytosomes dispersed in the shape memory gels can be considered as a promising therapeutic delivery system for protecting the skin from oxidation and reactive oxygen species. Full article

(This article belongs to the Special Issue Modification of Hydrogels and Their Applications in Biomedical Engineering)

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14 pages, 5918 KiB

Open AccessArticle

Development of Growth Factor Releasing Hyaluronic Acid-Based Hydrogel for Pulp Regeneration: A Preliminary Study

by Mi Sun Kim, Yu-Shik Hwang, Hyo-Seol Lee, Ok Hyung Nam and Sung Chul Choi

Gels 2022, 8(12), 825; https://doi.org/10.3390/gels8120825 - 13 Dec 2022

Cited by 3 | Viewed by 1683

Abstract

Growth factors play essential roles as signaling molecules in pulp regeneration. We investigated the effect of a hyaluronic acid (HA)-collagen hybrid hydrogel with controlled release of fibroblast growth factor (FGF)-2 and platelet-derived growth factor (PDGF)-BB on human pulp regeneration. The cell interaction and cytotoxicity of the HA-collagen hybrid hydrogel, the release kinetics of each growth factor, and the effects of the released growth factors on pulp cell proliferation were examined. The vitality of pulp cells was maintained. The amounts of FGF-2 and PDGF-BB released over 7 days were 68% and 50%, respectively. Groups with a different concentration of growth factor (FGF-2: 100, 200, 500, and 1000 ng/mL; PDGF-BB: 10, 50, 100, 200, and 500 ng/mL) were experimented on days 1, 3, 5, and 7. Considering FGF-2 concentration, significantly increased pulp cell proliferation was observed on days 1, 3, 5, and 7 in the 100 ng/mL group and on days 3, 5, and 7 in the 200 ng/mL group. In the case of PDGF-BB concentration, significantly increased pulp cell proliferation was observed at all four time points in the 100 ng/mL group and on days 3, 5, and 7 in the 50, 200, and 500 ng/mL groups. This indicates that the optimal concentration of FGF-2 and PDGF-BB for pulp cell proliferation was 100 ng/mL and that the HA-collagen hybrid hydrogel has potential as a controlled release delivery system for FGF-2 and PDGF-BB. Full article

(This article belongs to the Special Issue Modification of Hydrogels and Their Applications in Biomedical Engineering)

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13 pages, 4270 KiB

Open AccessArticle

Hydroxyapatite Reinforced Polyvinyl Alcohol/Polyvinyl Pyrrolidone Based Hydrogel for Cartilage Replacement

by Mallikarjun B. Jalageri and G. C. Mohan Kumar

Gels 2022, 8(9), 555; https://doi.org/10.3390/gels8090555 - 01 Sep 2022

Cited by 13 | Viewed by 2527

Abstract

Polyvinyl alcohol (PVA) and Polyvinyl Pyrrolidone (PVP) hydrogels are desirable biomaterials for soft tissue repair and replacement. However, the bio-inertness and poor cell adhesive potency of the PVA and PVP hinder the wide range of biomedical applications. In the present work, PVA and PVP were blended with a one-dimensional hydroxyapatite nanorod (HNr), and PVA/PVP/HNr composite hydrogel was synthesized by the freeze-thaw process. The developed hydrogels were characterized by Scanning Electron Microscope (SEM). The bio-ceramic nanohydroxyapatite content was optimized, and it was found that reinforcement improves mechanical strength as well as bioactivity. The compression strength values are 2.47 ± 0.73 MPa for the composite having 2 wt% of nanohydroxyapatite. The storage modulus was much higher than the loss modulus, which signifies the elastic dominancy similar to cartilage. Besides, the antimicrobial activity of nanohydroxyapatite reinforced PVA hydrogel towards bacterial species, Escherichia coli (E. Coli), Staphylococcus aureus (S. aureus) was satisfactory, and the in vitro biocompatibility response towards Human Mesenchymal stem cells(hMSC) after 72 h of culture confirms nanohydroxyapatite reinforced PVA/PVP hydrogels are the promising alternatives for next-generation cartilage substitutes. Full article

(This article belongs to the Special Issue Modification of Hydrogels and Their Applications in Biomedical Engineering)

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13 pages, 2548 KiB

Open AccessArticle

Tuning Myogenesis by Controlling Gelatin Hydrogel Properties through Hydrogen Peroxide-Mediated Cross-Linking and Degradation

by Wildan Mubarok, Kelum Chamara Manoj Lakmal Elvitigala and Shinji Sakai

Gels 2022, 8(6), 387; https://doi.org/10.3390/gels8060387 - 17 Jun 2022

Cited by 8 | Viewed by 2346

Abstract

Engineering skeletal muscle tissue in vitro is important to study the mechanism of myogenesis, which is crucial for regenerating muscle cells. The physicochemical properties of the cellular microenvironment are known to govern various cell behaviours. Yet, most studies utilised synthetic materials to model the extracellular matrix that suffers from cytotoxicity to the cells. We have previously reported that the physicochemical property of hydrogels obtained from horseradish peroxidase (HRP)-catalysed cross-linking could be controlled by a simple adjustment to the exposure time to air containing H₂O₂. In this study, we evaluated the influence of physicochemical properties dynamics in the gelatin possessing phenol groups (Gelatin-Ph) hydrogel to regulate the myogenesis in vitro. We controlled the Young’s modulus of the Gelatin-Ph hydrogel by tuning the air containing 16 ppm H₂O₂ exposure time for 15–60 min. Additionally, prolonged exposure to air containing H₂O₂ also induced Gelatin-Ph degradation. Myoblasts showed higher adhesion and myotube formation on stiff hydrogel (3.53 kPa) fabricated through 30 min of exposure to air containing H₂O₂ compared to those on softer hydrogel (0.77–2.79 kPa) fabricated through 15, 45, and 60 min of the exposure. These results demonstrate that the myogenesis can be tuned by changes in the physicochemical properties of Gelatin-Ph hydrogel mediated by H₂O₂. Full article

(This article belongs to the Special Issue Modification of Hydrogels and Their Applications in Biomedical Engineering)

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17 pages, 2268 KiB

Open AccessEditor’s ChoiceArticle

RGD-Functionalized Hydrogel Supports the Chondrogenic Commitment of Adipose Mesenchymal Stromal Cells

by Cristina Manferdini, Diego Trucco, Yasmin Saleh, Elena Gabusi, Paolo Dolzani, Enrico Lenzi, Lorenzo Vannozzi, Leonardo Ricotti and Gina Lisignoli

Gels 2022, 8(6), 382; https://doi.org/10.3390/gels8060382 - 15 Jun 2022

Cited by 9 | Viewed by 6531

Abstract

Articular cartilage is known to have limited intrinsic self-healing capacity when a defect or a degeneration process occurs. Hydrogels represent promising biomaterials for cell encapsulation and injection in cartilage defects by creating an environment that mimics the cartilage extracellular matrix. The aim of this study is the analysis of two different concentrations (1:1 and 1:2) of VitroGel^® (VG) hydrogels without (VG-3D) and with arginine-glycine-aspartic acid (RGD) motifs, (VG-RGD), verifying their ability to support chondrogenic differentiation of encapsulated human adipose mesenchymal stromal cells (hASCs). We analyzed the hydrogel properties in terms of rheometric measurements, cell viability, cytotoxicity, and the expression of chondrogenic markers using gene expression, histology, and immunohistochemical tests. We highlighted a shear-thinning behavior of both hydrogels, which showed good injectability. We demonstrated a good morphology and high viability of hASCs in both hydrogels. VG-RGD 1:2 hydrogels were the most effective, both at the gene and protein levels, to support the expression of the typical chondrogenic markers, including collagen type 2, SOX9, aggrecan, glycosaminoglycan, and cartilage oligomeric matrix protein and to decrease the proliferation marker MKI67 and the fibrotic marker collagen type 1. This study demonstrated that both hydrogels, at different concentrations, and the presence of RGD motifs, significantly contributed to the chondrogenic commitment of the laden hASCs. Full article

(This article belongs to the Special Issue Modification of Hydrogels and Their Applications in Biomedical Engineering)

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19 pages, 4400 KiB

Open AccessArticle

Advanced CNC/PEG/PDMAA Semi-IPN Hydrogel for Drug Delivery Management in Wound Healing

by Samia Afrin, Md. Shahruzzaman, Papia Haque, Md. Sazedul Islam, Shafiul Hossain, Taslim Ur Rashid, Tanvir Ahmed, Makoto Takafuji and Mohammed Mizanur Rahman

Gels 2022, 8(6), 340; https://doi.org/10.3390/gels8060340 - 30 May 2022

Cited by 8 | Viewed by 3370

Abstract

A Semi Interpenetrating Polymer Network (semi-IPN) hydrogel was prepared and loaded with an antibiotic drug, gentamicin, to investigate the wound healing activity of this system. The semi-IPN hydrogel was synthesized by combining natural polymer cellulose nanocrystal (CNC) and synthetic polymer polyethylene glycol (PEG) and poly (N,N′-dimethyl acrylamide) (PDMAA), which was initially added as a monomer dimethyl acrylamide (DMAA). CNC was prepared from locally obtained jute fibers, dispersed in a PEG-NaOH solvent system and then mixed with monomer DMAA, where polymerization was initiated by an initiator potassium persulphate (KPS) and cross-linked by N,N′-methylenebisacrylamide (NMBA). The size, morphology, biocompatibility, antimicrobial activity, thermal and swelling properties of the hydrogel were investigated by different characterization techniques. The biocompatibility of the hydrogel was confirmed by cytotoxicity analysis, which showed >95% survival of the BHK-21, Vero cell line. The drug loaded hydrogel showed antimicrobial property by forming 25 and 23 mm zone of inhibition against Staphylococcus aureus (gram-positive) and Escherichia coli (gram-negative) bacteria, respectively, in antimicrobial analysis. At pH 5.5, 76% of the drug was released from the hydrogel within 72 h, as observed in an in vitro drug release profile. In an in vivo test, the healing efficiency of the drug loaded hydrogel was examined on a mice model with dorsal wounds. Complete healing of the wound without any scar formation was achieved in 12 days, which revealed excellent wound healing properties of the prepared drug loaded semi-IPN hydrogel. These results showed the relevance of such a system in the rapid healing of acute wounds. Full article

(This article belongs to the Special Issue Modification of Hydrogels and Their Applications in Biomedical Engineering)

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20 pages, 3637 KiB

Open AccessArticle

Multi-Responsive Optimization of Novel pH-Sensitive Hydrogel Beads Based on Basil Seed Mucilage, Alginate, and Magnetic Particles

by Natwat Srikhao, Korrapat Chirochrapas, Nessaraporn Kwansanei, Pornnapa Kasemsiri, Artjima Ounkaew, Manunya Okhawilai, Chutiwat Likitaporn, Somnuk Theerakulpisut and Hiroshi Uyama

Gels 2022, 8(5), 274; https://doi.org/10.3390/gels8050274 - 27 Apr 2022

Cited by 9 | Viewed by 2362

Abstract

Conventional drug delivery systems often cause side effects and gastric degradation. Novel drug delivery systems must be developed to decrease side effects and increase the efficacy of drug delivery. This research aimed to fabricate hydrogel beads for use as a drug delivery system based on basil seed mucilage (BSM), sodium alginate (SA), and magnetic particles (MPs). The Taguchi method and Grey relational analysis were used for the design and optimization of the hydrogel beads. Three factors, including BSM, SA, and MPs at four levels were designed by L-16 orthogonal arrays. BSM was the main factor influencing bead swelling, drug release rate at pH 7.4, and release of antioxidants at pH 1.2 and 7.4. In addition, SA and MPs mainly affected drug loading and drug release rate in acidic medium, respectively. Grey relational analysis indicated that the composition providing optimal overall properties was 0.2 vol% BSM, 0.8 vol% SA, and 2.25 vol% MPs. Based on the findings of this work, BSM/SA/MPs hydrogel beads have the potential to be used as a pH-sensitive alternative material for drug delivery in colon-specific systems. Full article

(This article belongs to the Special Issue Modification of Hydrogels and Their Applications in Biomedical Engineering)

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14 pages, 3125 KiB

Open AccessArticle

Soft-Tissue-Mimicking Using Hydrogels for the Development of Phantoms

by Aitor Tejo-Otero, Felip Fenollosa-Artés, Isabel Achaerandio, Sergi Rey-Vinolas, Irene Buj-Corral, Miguel Ángel Mateos-Timoneda and Elisabeth Engel

Gels 2022, 8(1), 40; https://doi.org/10.3390/gels8010040 - 06 Jan 2022

Cited by 30 | Viewed by 5344

Abstract

With the currently available materials and technologies it is difficult to mimic the mechanical properties of soft living tissues. Additionally, another significant problem is the lack of information about the mechanical properties of these tissues. Alternatively, the use of phantoms offers a promising solution to simulate biological bodies. For this reason, to advance in the state-of-the-art a wide range of organs (e.g., liver, heart, kidney as well as brain) and hydrogels (e.g., agarose, polyvinyl alcohol –PVA–, Phytagel –PHY– and methacrylate gelatine –GelMA–) were tested regarding their mechanical properties. For that, viscoelastic behavior, hardness, as well as a non-linear elastic mechanical response were measured. It was seen that there was a significant difference among the results for the different mentioned soft tissues. Some of them appear to be more elastic than viscous as well as being softer or harder. With all this information in mind, a correlation between the mechanical properties of the organs and the different materials was performed. The next conclusions were drawn: (1) to mimic the liver, the best material is 1% wt agarose; (2) to mimic the heart, the best material is 2% wt agarose; (3) to mimic the kidney, the best material is 4% wt GelMA; and (4) to mimic the brain, the best materials are 4% wt GelMA and 1% wt agarose. Neither PVA nor PHY was selected to mimic any of the studied tissues. Full article

(This article belongs to the Special Issue Modification of Hydrogels and Their Applications in Biomedical Engineering)

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Review

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45 pages, 3958 KiB

Open AccessReview

Poly(N-isopropylacrylamide)-Based Hydrogels for Biomedical Applications: A Review of the State-of-the-Art

by Mohammad Javed Ansari, Rahul R. Rajendran, Sourav Mohanto, Unnati Agarwal, Kingshuk Panda, Kishore Dhotre, Ravi Manne, A. Deepak, Ameeduzzafar Zafar, Mohd Yasir and Sheersha Pramanik

Gels 2022, 8(7), 454; https://doi.org/10.3390/gels8070454 - 20 Jul 2022

Cited by 56 | Viewed by 7263

Abstract

A prominent research topic in contemporary advanced functional materials science is the production of smart materials based on polymers that may independently adjust their physical and/or chemical characteristics when subjected to external stimuli. Smart hydrogels based on poly(N-isopropylacrylamide) (PNIPAM) demonstrate distinct thermoresponsive features close to a lower critical solution temperature (LCST) that enhance their capability in various biomedical applications such as drug delivery, tissue engineering, and wound dressings. Nevertheless, they have intrinsic shortcomings such as poor mechanical properties, limited loading capacity of actives, and poor biodegradability. Formulation of PNIPAM with diverse functional constituents to develop hydrogel composites is an efficient scheme to overcome these defects, which can significantly help for practicable application. This review reports on the latest developments in functional PNIPAM-based smart hydrogels for various biomedical applications. The first section describes the properties of PNIPAM-based hydrogels, followed by potential applications in diverse fields. Ultimately, this review summarizes the challenges and opportunities in this emerging area of research and development concerning this fascinating polymer-based system deep-rooted in chemistry and material science. Full article

(This article belongs to the Special Issue Modification of Hydrogels and Their Applications in Biomedical Engineering)

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