Injectable Gels: Applications in Drug Delivery and Tissue Engineering

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

Deadline for manuscript submissions: closed (30 October 2022) | Viewed by 24887

Special Issue Editors

Institute of Translational Medicine, Shanghai University, Shanghai 200444, China
Interests: biomaterials; cancer immunotherapy; tissue regeneration
Special Issues, Collections and Topics in MDPI journals
Engineering Research Centre for Biomedical Materials of Ministry of Education, Frontiers Science Center for Materiobiology and Dynamic Chemistry, East China University of Technology, Shanghai 200237, China
Interests: nano-biomaterials
Special Issues, Collections and Topics in MDPI journals
College of Chemical Engineering, Huaqiao University, Xiamen 361021, China
Interests: biomaterials; drug delivery; tissue engineering; 3D printing
Institute for Frontier Medical Technology, Shanghai University of Engineering Science, Shanghai 201620, China
Interests: biofunctional polymer materials; nanofibers; gel; drug delivery; tissue engineering
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Injectable gels represent a promising strategy for facilitating drug delivery and tissue engineering, and offer several advantages such as minimal invasion, targeted delivery, regenerating damaged tissues and organs, supporting cell proliferation and differentiation, and facilitating tissue growth. This Topic Collection “Injectable Gel Applications in Drug Delivery and Tissue Engineering” aims to collect high-quality research and review articles in all the fields of injectable gel materials, with a focus on drug delivery and tissue engineering. Since the aim of this Topic Collection is to illustrate people through selected work and frontier research in injectable gel materials science, we encourage materials scientists, chemists, or clinical investigators to contribute papers reflecting the latest progress in their research fields. The topics include, without being limited to:

  • Visualized functional injectable gels;
  • Stem cells, exosomes, and nanoparticle-loaded injectable gels;
  • 3D printing, electrospinning, and molding-based injectable gels;
  • Immune-regulated injectable gels;
  • Injectable DNA gels;
  • The mechanism and effect of physical/chemical crosslinked injectable gels;
  • Lubricant injectable hydrogels;

Prof. Dr. Jie Gao 

Prof. Dr. Yulin Li 

Prof. Dr. Yuangang Liu

Prof. Dr. Tonghe Zhu

Guest Editors


Manuscript Submission Information

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Published Papers (9 papers)

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Research

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12 pages, 4570 KiB  
Article
Pharmacodynamics of Dracorhodin Perchlorate and Its Inflammation-Targeting Emulsion Gel for Wound Healing
by Xiaojie Wang, Xue Guo, Ran Yu, Mingxing Yue, Xingjuan Li, Bo Liu and Zhiquan Pan
Gels 2022, 8(11), 712; https://0-doi-org.brum.beds.ac.uk/10.3390/gels8110712 - 04 Nov 2022
Viewed by 2372
Abstract
The mechanism of dracorhodin perchlorate for the repair of rat skin wounds was investigated. In order to screen a more favorable drug delivery system for wound repair, the therapeutic effect of dracorhodin perchlorate inflammation-targeted emulsion gel was compared with that of non-targeted emulsion [...] Read more.
The mechanism of dracorhodin perchlorate for the repair of rat skin wounds was investigated. In order to screen a more favorable drug delivery system for wound repair, the therapeutic effect of dracorhodin perchlorate inflammation-targeted emulsion gel was compared with that of non-targeted emulsion gel on rat wounds. Compared with non-targeted emulsion gels, inflammation-targeted emulsion gels had a better transdermal penetration and lower potentials (−51.6 mV and −17.1 mV, respectively). The recovery of the wound from the dracorhodin perchlorate inflammation targeted emulsion gel group was better than that of the dracorhodin perchlorate inflammation non-targeted emulsion gel group and the positive drug group. Compared with the no-target emulsion gel group, the bFGF expression on day 7 and the EGF expression on day 14 in the targeted emulsion group showed 45.5% and 49.9% improvement, respectively. Pathological tissue slices showed that the epidermis, dermis, and basal layer inflammatory cells in the inflammation-targeted emulsion gel group and non-targeted emulsion gel group were significantly reduced, the granulation tissue proliferation was obvious, and the inflammation-targeted emulsion gel group was more effective. The results proved that dracorhodin perchlorate had a repairing effect on rat skin wounds, and its mechanism might be related to the promotion of the expression of EGF and bFGF in tissues. Full article
(This article belongs to the Special Issue Injectable Gels: Applications in Drug Delivery and Tissue Engineering)
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17 pages, 1550 KiB  
Article
Magnetically Activated Piezoelectric 3D Platform Based on Poly(Vinylidene) Fluoride Microspheres for Osteogenic Differentiation of Mesenchymal Stem Cells
by Maria Guillot-Ferriols, María Inmaculada García-Briega, Laia Tolosa, Carlos M. Costa, Senentxu Lanceros-Méndez, José Luis Gómez Ribelles and Gloria Gallego Ferrer
Gels 2022, 8(10), 680; https://0-doi-org.brum.beds.ac.uk/10.3390/gels8100680 - 20 Oct 2022
Cited by 3 | Viewed by 2170
Abstract
Mesenchymal stem cells (MSCs) osteogenic commitment before injection enhances bone regeneration therapy results. Piezoelectric stimulation may be an effective cue to promote MSCs pre-differentiation, and poly(vinylidene) fluoride (PVDF) cell culture supports, when combined with CoFe2O4 (CFO), offer a wireless in [...] Read more.
Mesenchymal stem cells (MSCs) osteogenic commitment before injection enhances bone regeneration therapy results. Piezoelectric stimulation may be an effective cue to promote MSCs pre-differentiation, and poly(vinylidene) fluoride (PVDF) cell culture supports, when combined with CoFe2O4 (CFO), offer a wireless in vitro stimulation strategy. Under an external magnetic field, CFO shift and magnetostriction deform the polymer matrix varying the polymer surface charge due to the piezoelectric effect. To test the effect of piezoelectric stimulation on MSCs, our approach is based on a gelatin hydrogel with embedded MSCs and PVDF-CFO electroactive microspheres. Microspheres were produced by electrospray technique, favouring CFO incorporation, crystallisation in β-phase (85%) and a crystallinity degree of around 55%. The absence of cytotoxicity of the 3D construct was confirmed 24 h after cell encapsulation. Cells were viable, evenly distributed in the hydrogel matrix and surrounded by microspheres, allowing local stimulation. Hydrogels were stimulated using a magnetic bioreactor, and no significant changes were observed in MSCs proliferation in the short or long term. Nevertheless, piezoelectric stimulation upregulated RUNX2 expression after 7 days, indicating the activation of the osteogenic differentiation pathway. These results open the door for optimising a stimulation protocol allowing the application of the magnetically activated 3D electroactive cell culture support for MSCs pre-differentiation before transplantation. Full article
(This article belongs to the Special Issue Injectable Gels: Applications in Drug Delivery and Tissue Engineering)
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11 pages, 1230 KiB  
Article
The Effect of Sulfobetaine Coating in Inhibiting the Interaction between Lyotropic Liquid Crystalline Nanogels and Proteins
by Ziqiao Zhong, Zhiwei Chen, Yuke Xie, Wenhao Wang, Zhengwei Huang, Ying Huang, Chuanbin Wu and Xin Pan
Gels 2022, 8(10), 653; https://0-doi-org.brum.beds.ac.uk/10.3390/gels8100653 - 14 Oct 2022
Viewed by 1267
Abstract
The injective lyotropic liquid crystalline nanogels (LLCNs) were widely used in drug delivery systems. But when administered in vivo, LLCNs exposed to the biological environment interact with proteins. Recently, it has been shown that nanoparticles coated with zwitterions can inhibit their interaction with [...] Read more.
The injective lyotropic liquid crystalline nanogels (LLCNs) were widely used in drug delivery systems. But when administered in vivo, LLCNs exposed to the biological environment interact with proteins. Recently, it has been shown that nanoparticles coated with zwitterions can inhibit their interaction with proteins. Thus, in this study, the interaction between proteins and LLCNs coated with the zwitterionic material sulfobetaine (GLLCNs@HDSB) was investigated using bovine serum albumin (BSA) as a model protein. Interestingly, it was found that GLLCNs@HDSB at higher concentrations (≥0.8 mg/mL) could block its interaction with BSA, but not at lower concentrations (<0.8 mg/mL), according to the results of ultraviolet, fluorescence, and circular dichroism spectra. In the ultraviolet spectra, the absorbance of GLLCNs@HDSB (0.8 mg/mL) was 1.9 times higher than that without the sulfobetaine coating (GLLCNs) after incubation with protein; the fluorescence quenching intensity of GLLCNs@HDSB was conversely larger than that of the GLLCNs; in circular dichroism spectra, the ellipticity value of GLLCNs@HDSB was significantly smaller than that of the GLLCNs, and the change in GLLCNs@HDSB was 10 times higher than that of the GLLCNs. Generally, nanoparticles coated with sulfobetaine can inhibit their interaction with proteins, but in this study, LLCNs showed a concentration-dependent inhibitory effect. It could be inferred that in contrast to the surface of nanoparticles covered with sulfobetaine in other cases, the sulfobetaine in this study interacted with the LLCNs and was partially inserted into the hydrophobic region of the LLCNs. In conclusion, this study suggests that coating-modified nanoparticles do not necessarily avoid interacting with proteins, and we should also study coating-modified nanoparticles interacting with proteins both in vitro and in vivo. In the future, finding a coating material to completely inhibit the interaction between LLCNs and proteins will generate a great impetus to promote the clinical transformation of LLCNs. Full article
(This article belongs to the Special Issue Injectable Gels: Applications in Drug Delivery and Tissue Engineering)
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18 pages, 4081 KiB  
Article
Quercetin-Embedded Gelastin Injectable Hydrogel as Provisional Biotemplate for Future Cutaneous Application: Optimization and In Vitro Evaluation
by Mazlan Zawani, Manira Maarof, Yasuhiko Tabata, Antonella Motta and Mh Busra Fauzi
Gels 2022, 8(10), 623; https://0-doi-org.brum.beds.ac.uk/10.3390/gels8100623 - 29 Sep 2022
Cited by 10 | Viewed by 1865
Abstract
Chronic wounds have become an epidemic in millions of patients and result in amputations. In order to overcome this, immediate treatment is a realistic strategy to minimize the risk of complications and aid in the healing rate of the cutaneous wound. Functionalized engineered [...] Read more.
Chronic wounds have become an epidemic in millions of patients and result in amputations. In order to overcome this, immediate treatment is a realistic strategy to minimize the risk of complications and aid in the healing rate of the cutaneous wound. Functionalized engineered biomaterials are proven to be a potential approach to embarking on skin wound management. Thus, this study aimed to evaluate the efficacy of a quercetin-embedded gelatin–elastin (Gelastin) injectable hydrogel to act as a provisional biotemplate with excellent physicochemical properties, to be utilized for future cutaneous application. Briefly, the hydrogel was homogenously pre-mixed with genipin (GNP), followed by the incorporation of quercetin (QC). The physicochemical properties comprised the contact angle, swelling ratio, crosslinking degree, enzymatic biodegradation, and water vapor transmission rate (WVTR), as well as chemical characterization. Energy-dispersive X-ray (EDX), XRD, and Fourier transform infra-red (FTIR) analyses were conducted. Briefly, the findings demonstrated that the crosslinked hybrid biomatrix demonstrated better resilience at >100%, a contact angle of >20°, a swelling ratio average of 500 ± 10%, a degradation rate of <0.05 mg/hour, and a successful crosslinking degree (<70%free amine group), compared to the non-crosslinked hybrid biomatrix. In addition, the WVTR was >1500 g/m2 h, an optimal moisture content designed to attain regular cell function and proliferation. The outcomes convey that Gelastin-QC hydrogels deliver the optimum features to be used as a provisional biotemplate for skin tissue engineering purposes. Full article
(This article belongs to the Special Issue Injectable Gels: Applications in Drug Delivery and Tissue Engineering)
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16 pages, 4932 KiB  
Article
A dZnONPs Enhanced Hybrid Injectable Photocrosslinked Hydrogel for Infected Wounds Treatment
by Yao Chen, Yu Xiang, Tonghe Zhu, Sihao Chen, Juan Du, Jiajia Luo and Xiaoyu Yan
Gels 2022, 8(8), 463; https://0-doi-org.brum.beds.ac.uk/10.3390/gels8080463 - 24 Jul 2022
Cited by 2 | Viewed by 1885
Abstract
Chronic wounds caused by related diseases such as ischemia, diabetes, and venous stasis are often hard to manage, mainly because of their susceptibility to infection and the lack of healing-promoting growth factors. Functional hydrogel is a promising material for wound treatment due to [...] Read more.
Chronic wounds caused by related diseases such as ischemia, diabetes, and venous stasis are often hard to manage, mainly because of their susceptibility to infection and the lack of healing-promoting growth factors. Functional hydrogel is a promising material for wound treatment due to its regulable swelling rate and its ability to absorb wound exudate, which can keep the wound isolated from the outside world to prevent infection. In this study, a photocrosslinked physicochemical double-network hydrogel with injectable, antibacterial, and excellent mechanical properties was prepared. The dZnONPs enhanced hybrid injectable photocrosslinked double-network hydrogel (Ebs@dZnONPs/HGT) was synthetized starting from acylated hyaluronic acid and tannic acid via free radical reaction and hydrogen bonding, following doped with ebselen (Ebs) loaded dendritic zinc oxide nanoparticles (dZnONPs) to prepare the Ebs@dZnONPs/HGT hydrogel. The physicochemical characterization confirmed that the Ebs@dZnONPs/HGT hydrogel had excellent mechanical properties, hydrophilicity, and injectable properties, and could fit irregular wounds well. In vitro experiments revealed that the Ebs@dZnONPs/HGT hydrogel presented credible cytocompatibility and prominent antibacterial activity against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). In vivo experiments further demonstrated that the Ebs@dZnONPs/HGT hydrogel had excellent biosafety and could improve re-epithelialization in the wound area, thus significantly accelerating wound healing. Full article
(This article belongs to the Special Issue Injectable Gels: Applications in Drug Delivery and Tissue Engineering)
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13 pages, 3322 KiB  
Article
Chiral Supramolecular Hydrogel Loaded with Dimethyloxalyglycine to Accelerate Chronic Diabetic Wound Healing by Promoting Cell Proliferation and Angiogenesis
by Yubo Zhang, Weijie Cai, Zun Ren, Yuxiang Lu, Musha Hamushan, Pengfei Cheng, Zhengyu Xu, Hao Shen, Changli Zhao, Pei Han and Wanrun Zhong
Gels 2022, 8(7), 437; https://0-doi-org.brum.beds.ac.uk/10.3390/gels8070437 - 13 Jul 2022
Cited by 5 | Viewed by 2158
Abstract
Chronic refractory wounds are one of the most serious complications of diabetes, and the effects of common treatments are limited. Chiral hydrogel combined with dimethyloxalyglycine (DMOG) as a dressing is a promising strategy for the treatment of chronic wounds. In this research, we [...] Read more.
Chronic refractory wounds are one of the most serious complications of diabetes, and the effects of common treatments are limited. Chiral hydrogel combined with dimethyloxalyglycine (DMOG) as a dressing is a promising strategy for the treatment of chronic wounds. In this research, we have developed a DMOG-loaded supramolecular chiral amino-acid-derivative hydrogel for wound dressings for full-thickness skin regeneration of chronic wounds. The properties of the materials, the ability of sustained release drugs, and the ability to promote angiogenesis were tested in vitro, and the regeneration rate and repair ability of full-thickness skin were tested in vivo. The chiral hydrogel had the ability to release drugs slowly. It can effectively promote cell migration and angiogenesis in vitro, and promote full-thickness skin regeneration and angiogenesis in vivo. This work offers a new approach for repairing chronic wounds completely through a supramolecular chiral hydrogel loaded with DMOG. Full article
(This article belongs to the Special Issue Injectable Gels: Applications in Drug Delivery and Tissue Engineering)
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20 pages, 5016 KiB  
Article
Drug Delivery from Hyaluronic Acid–BDDE Injectable Hydrogels for Antibacterial and Anti-Inflammatory Applications
by Jon Andrade del Olmo, Leyre Pérez-Álvarez, Virginia Sáez Martínez, Sandra Benito Cid, Raúl Pérez González, José Luis Vilas-Vilela and José María Alonso
Gels 2022, 8(4), 223; https://0-doi-org.brum.beds.ac.uk/10.3390/gels8040223 - 06 Apr 2022
Cited by 13 | Viewed by 5228
Abstract
Hyaluronic acid (HA) injectable biomaterials are currently applied in numerous biomedical areas, beyond their use as dermal fillers. However, bacterial infections and painful inflammations are associated with healthcare complications that can appear after injection, restricting their applicability. Fortunately, HA injectable hydrogels can also [...] Read more.
Hyaluronic acid (HA) injectable biomaterials are currently applied in numerous biomedical areas, beyond their use as dermal fillers. However, bacterial infections and painful inflammations are associated with healthcare complications that can appear after injection, restricting their applicability. Fortunately, HA injectable hydrogels can also serve as drug delivery platforms for the controlled release of bioactive agents with a critical role in the control of certain diseases. Accordingly, herein, HA hydrogels were crosslinked with 1 4-butanediol diglycidyl ether (BDDE) loaded with cefuroxime (CFX), tetracycline (TCN), and amoxicillin (AMX) antibiotics and acetylsalicylic acid (ASA) anti-inflammatory agent in order to promote antibacterial and anti-inflammatory responses. The hydrogels were thoroughly characterized and a clear correlation between the crosslinking grade and the hydrogels’ physicochemical properties was found after rheology, scanning electron microscopy (SEM), thermogravimetry (TGA), and differential scanning calorimetry (DSC) analyses. The biological safety of the hydrogels, expected due to the lack of BDDE residues observed in 1H-NMR spectroscopy, was also corroborated by an exhaustive biocompatibility test. As expected, the in vitro antibacterial and anti-inflammatory activity of the drug-loaded HA-BDDE hydrogels was confirmed against Staphylococcus aureus by significantly decreasing the pro-inflammatory cytokine levels. Full article
(This article belongs to the Special Issue Injectable Gels: Applications in Drug Delivery and Tissue Engineering)
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19 pages, 21858 KiB  
Article
Lime Peel Oil–Incorporated Rosin-Based Antimicrobial In Situ Forming Gel
by Ei Mon Khaing, Jongjan Mahadlek, Siriporn Okonogi and Thawatchai Phaechamud
Gels 2022, 8(3), 169; https://0-doi-org.brum.beds.ac.uk/10.3390/gels8030169 - 08 Mar 2022
Cited by 13 | Viewed by 2519
Abstract
Localized intra-periodontal pocket drug delivery using an injectable in situ forming gel is an effective periodontitis treatment. The aqueous insoluble property of rosin is suitable for preparing a solvent exchange-induced in situ forming gel. This study aims to investigate the role of incorporating [...] Read more.
Localized intra-periodontal pocket drug delivery using an injectable in situ forming gel is an effective periodontitis treatment. The aqueous insoluble property of rosin is suitable for preparing a solvent exchange-induced in situ forming gel. This study aims to investigate the role of incorporating lime peel oil (LO) on the physicochemical properties of injectable in situ forming gels based on rosin loaded with 5% w/w doxycycline hyclate (DH) in dimethyl sulfoxide (DMSO) and N-methyl pyrrolidone (NMP). Their gel formation, viscosity, injectability, mechanical properties, wettability, drug release, and antimicrobial activities were evaluated. The presence of LO slowed gel formation due to the loose precipitate formation of gel with a high LO content. The viscosity and injectability were slightly increased with higher LO content for the DH-loaded rosin-based in situ forming gel. The addition of 10% LO lowered gel hardness with higher adhesion. LO incorporation promoted a higher drug release pattern than the no oil-added formulation over 10 days and the gel formation rate related to burst drug release. The drug release kinetics followed the non-Fickian diffusion mechanism for oil-added formulations. LO exhibited high antimicrobial activity against Porphyromonas gingivalis and Staphylococcus aureus. The DH-loaded rosin in situ forming gel with an addition of LO (0, 2.5, 5, and 10% w/w) inhibited all tested microorganisms. Adding 10% LO to rosin-based in situ forming gel improved the antimicrobial activities, especially for the P. gingivalis and S. aureus. As a result, the study demonstrates the possibility of using an LO amount of less than 10% loading into a rosin-based in situ forming gel for efficient periodontitis treatment. Full article
(This article belongs to the Special Issue Injectable Gels: Applications in Drug Delivery and Tissue Engineering)
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Review

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17 pages, 4624 KiB  
Review
Injectable DNA Hydrogel-Based Local Drug Delivery and Immunotherapy
by Qi Wang, Yanfei Qu, Ziyi Zhang, Hao Huang, Yufei Xu, Fengyun Shen, Lihua Wang and Lele Sun
Gels 2022, 8(7), 400; https://0-doi-org.brum.beds.ac.uk/10.3390/gels8070400 - 24 Jun 2022
Cited by 12 | Viewed by 3454
Abstract
Regulated drug delivery is an important direction in the field of medicine and healthcare research. In recent years, injectable hydrogels with good biocompatibility and biodegradability have attracted extensive attention due to their promising application in controlled drug release. Among them, DNA hydrogel has [...] Read more.
Regulated drug delivery is an important direction in the field of medicine and healthcare research. In recent years, injectable hydrogels with good biocompatibility and biodegradability have attracted extensive attention due to their promising application in controlled drug release. Among them, DNA hydrogel has shown great potentials in local drug delivery and immunotherapy. DNA hydrogel is a three-dimensional network formed by cross-linking of hydrophilic DNA strands with extremely good biocompatibility. Benefiting from the special properties of DNA, including editable sequence and specificity of hybridization reactions, the mechanical properties and functions of DNA hydrogels can be precisely designed according to specific applications. In addition, other functional materials, including peptides, proteins and synthetic organic polymers can be easily integrated with DNA hydrogels, thereby enriching the functions of the hydrogels. In this review, we first summarize the types and synthesis methods of DNA hydrogels, and then review the recent research progress of injectable DNA hydrogels in local drug delivery, especially in immunotherapy. Finally, we discuss the challenges facing DNA hydrogels and future development directions. Full article
(This article belongs to the Special Issue Injectable Gels: Applications in Drug Delivery and Tissue Engineering)
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