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Immunomodulation and Smart Materials for the Application of Maxillofacial Surgery

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A special issue of Applied Sciences (ISSN 2076-3417). This special issue belongs to the section "Applied Biosciences and Bioengineering".

Deadline for manuscript submissions: closed (21 January 2022) | Viewed by 32449

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Prof. Dr. Seong-Gon Kim

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Department of Oral and Maxillofacial Surgery, Gangneung-Wonju National University, 123 Jibyeon-dong, Gangneung, Gangwon-do, Republic of Korea
Interests: tissue engineering
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Special Issue Information

Dear Colleagues,

This Special Issue is devoted to immunomodulation and the development of smart materials in the maxillofacial surgery field. Considering the wide application of these materials, fundamental research and toxicological concerns are also welcomed. In the immunomodulation, any materials inducing M1 or M2 type macrophages should be helpful for tissue regeneration. Classical approaches such as the modification of surface and porosity can also be considered. For guided differentiation, cytokines such as TGF-β1, VEGF, PDGF, and BMPs can be considered as active ingredients. As an emerging material for M2 induction, research associated with 4-hexylresorcinol is also welcome. For the optimal delivery of active ingredients, smart materials should also be developed. The rationale for this innovation is the improvement of quality of life for patients with maxillofacial defects.

Prof. Dr. Seong-Gon Kim
Guest Editor

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Keywords

immunomodulation
smart materials
macrophage
4-hexylresorcinol

Published Papers (14 papers)

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Editorial

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3 pages, 167 KiB

Open AccessEditorial

Special Issue on Immunomodulation and Smart Materials for the Application of Maxillofacial Surgery

by Seong-Gon Kim

Appl. Sci. 2023, 13(9), 5734; https://doi.org/10.3390/app13095734 - 06 May 2023

Viewed by 657

Abstract

Immunomodulation in tissue engineering involves the deliberate manipulation or regulation of the immune system's response to aid in tissue regeneration, repair, or the incorporation of engineered constructs within the body [...] Full article

(This article belongs to the Special Issue Immunomodulation and Smart Materials for the Application of Maxillofacial Surgery)

Research

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15 pages, 2446 KiB

Open AccessArticle

Increased Expression of TGF-β1 by 4-hexylresorcinol Is Mediated by Endoplasmic Reticulum and Mitochondrial Stress in Human Umbilical Endothelial Vein Cells

by Jwa-Young Kim, Dae-Won Kim, Suk Keun Lee, Je-Yong Choi, Xiangguo Che, Seong-Gon Kim and Umberto Garagiola

Appl. Sci. 2021, 11(19), 9128; https://doi.org/10.3390/app11199128 - 30 Sep 2021

Cited by 8 | Viewed by 1414

Abstract

In our previous study, 4-hexylresorcinol (4HR) increased the expression level of vascular endothelial growth factor in human umbilical vein endothelial cells (HUVECs) via the transforming growth factor-β1 (TGF-β1)-mediated pathway. Endoplasmic reticulum (ER) and mitochondrial stress is a positive regulator of cellular differentiation. As TGF-β1 is a master regulator for cellular differentiation, 4HR treatment may increase TGF-β1 expression via ER stress. In this study, HUVECs were treated using 4HR (1–100 μM) for 24 h. The 4HR treatment increased ER stress-associated markers and mitochondrial stress. Increased TGF-β1 expression by 4HR administration was alleviated by tauroursodeoxycholate (ER stress inhibitor) treatment. Combining these activities with the elevated acetylation level of histone 3 (H3) by 4HR treatment, TGF-β1 expression was increased in HUVECs. Overall, 4HR increased TGF-β1 expression through upregulation of the stress response of ER as well as H3 acetylation in HUVECs. Full article

(This article belongs to the Special Issue Immunomodulation and Smart Materials for the Application of Maxillofacial Surgery)

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9 pages, 1177 KiB

Open AccessArticle

Stability of the Natural Joint Side in Unilateral Alloplastic Total Temporomandibular Joint Replacement Using a Ready-Made System

by Jin-Hong Kim, Byung-Ho Park, Myoung-Sang Yoo and Bu-Kyu Lee

Appl. Sci. 2021, 11(9), 3935; https://doi.org/10.3390/app11093935 - 27 Apr 2021

Cited by 5 | Viewed by 3035

Abstract

An alloplastic total joint replacement (TJR) is an effective and reliable treatment option in non-salvageable end-stage temporomandibular joint (TMJ) disease. However, unilateral alloplastic TJR of the TMJ (TMJ TJR) could affect the other side natural joint because the physiologic action of both condyles is quite different during mandibular movement. In this study, we examined whether the unilaterally replaced alloplastic TMJ TJR affects the other side natural joint condition over long periods of time. Eight patients who received alloplastic TJR on one side were subjects in this study. All alloplastic TJR implants were stable in situ. The average maximum mouth opening was 37.5 mm (range 19–49 mm) pre-operatively and 44.1 mm (range 34–57 mm) post-operatively. This parameter gradually increased and reached the maximum at about twelve months after surgery. The post-operative change of pain level was significantly reduced from 3.5 to 0 on a pain scale of zero to ten. No significant complications in any joints were observed within the follow-up period. The shape of the natural joint sides showed slight changes but were functionally stable during the observation period. In this study, unilateral alloplastic TJR showed stable and reliable clinical results, either alloplastic TJR or healthy joint sides for quite long period of time. Full article

(This article belongs to the Special Issue Immunomodulation and Smart Materials for the Application of Maxillofacial Surgery)

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10 pages, 1701 KiB

Open AccessArticle

Alleviation of Oxidative Stress in Dental Pulp Cells Following 4-Hexylresorcinol Administration in a Rat Model

by Jun-Ho Chang, Dae-Won Kim, Seong-Gon Kim and Tae-Woo Kim

Appl. Sci. 2021, 11(8), 3637; https://doi.org/10.3390/app11083637 - 18 Apr 2021

Cited by 5 | Viewed by 1551

Abstract

Damaged dental pulp undergoes oxidative stress and 4-hexylresorcinol (4HR) is a well-known antioxidant. In this study, we aimed to evaluate the therapeutic effects of a 4HR ointment on damaged dental pulp. Pulp cells from rat mandibular incisor were cultured and treated with 4HR or resveratrol (1–100 μM). These treatments (10–100 μM) exerted a protective effect during subsequent hydrogen peroxide treatments. The total antioxidant capacity and glutathione peroxidase activity were significantly increased following 4HR or resveratrol treatment (p < 0.05), while the expression levels of TNF-α and IL1β were decreased following the exposure to 4HR pre-treatment in an in vitro model. Additionally, the application of 4HR ointment in an exposed dental pulp model significantly reduced the expression of TNF-α and IL1β (p < 0.05). Conclusively, 4HR exerted protective effects against oxidative stress in dental pulp tissues through downregulating TNF-α and IL1β. Full article

(This article belongs to the Special Issue Immunomodulation and Smart Materials for the Application of Maxillofacial Surgery)

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8 pages, 1289 KiB

Open AccessArticle

4-Hexylresorcinol Inhibits Class I Histone Deacetylases in Human Umbilical Cord Endothelial Cells

by Jwa-Young Kim, Hae-Yong Kweon, Dae-Won Kim, Je-Yong Choi and Seong-Gon Kim

Appl. Sci. 2021, 11(8), 3486; https://doi.org/10.3390/app11083486 - 13 Apr 2021

Cited by 11 | Viewed by 1684

Abstract

Histone deacetylases (HDACs) are key enzymes for post-translational modification and influence on various cellular activities. Thus, HDACs are associated with many diseases and their inhibitors have clinical significance. Here, 4-Hexylresorcinol (4HR) was studied as an inhibitor for class I HDACs using the HDAC inhibitor (HDACi) Trichostatin-A as a positive control. The 4HR was administered 1–100 μM to human umbilical endothelial cells (HUVECs) and the HDAC expression and activity were examined. The 4HR decreased the expression level of HDAC1, 3, 4, and 5 in a time and dose-dependent manner. The 4HR also increased acetylated lysine and decreased HDAC activity significantly (p < 0.05). Collectively, 4HR was a new class I HDAC inhibitor that reduced the expression and activity of HDAC in HUVECs. Full article

(This article belongs to the Special Issue Immunomodulation and Smart Materials for the Application of Maxillofacial Surgery)

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8 pages, 1085 KiB

Open AccessArticle

The Effect of Sericin on Bone Regeneration in a Streptozotocin-Induced Type I Diabetes Animal Model

by Khang Do Gia Hong, Yei-Jin Kang, Ji-Hyeon Oh, Seong-Gon Kim, Young-Wook Park, You-Young Jo, HaeYong Kweon and Horatiu Rotaru

Appl. Sci. 2021, 11(4), 1369; https://doi.org/10.3390/app11041369 - 03 Feb 2021

Cited by 3 | Viewed by 1510

Abstract

There is an association between diabetes and impaired bone healing. The purpose of this study was to determine whether sericin had a positive effect on bone regeneration with streptozotocin-induced diabetes in a rat model. Sprague Dawley rats (n = 21) were assigned to one of three groups. A critical-sized bone defect was created on the calvaria. In the sericin group (S group, n = 7), the bone defect was filled with a sericin–gelatin combination, whereas in the gelatin group (G group, n = 7), only gelatin sponge was used. The control group (N group, n = 7) did not receive any graft. New bone formation was evaluated by micro-computerized tomogram and histological analysis. The regenerated bone volume in group S was the highest among the three groups (3.87 ± 2.51 mm³), followed by group N (1.71 ± 1.65 mm³) and group G (1.24 ± 1.05 mm³). The application of sericin in combination with a gelatin sponge enhanced the process of bone regeneration in streptozotocin-induced type I diabetes animal model. Full article

(This article belongs to the Special Issue Immunomodulation and Smart Materials for the Application of Maxillofacial Surgery)

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12 pages, 3063 KiB

Open AccessArticle

Inhibitory Effects of 4-Hexylresorcinol on Root Resorption Induced by Orthodontic Tooth Movement

by Jun-Kyu Jang, Dae-Won Kim, Seong-Gon Kim and Tae-Woo Kim

Appl. Sci. 2020, 10(18), 6313; https://doi.org/10.3390/app10186313 - 10 Sep 2020

Cited by 5 | Viewed by 2069

Abstract

Root resorption during orthodontic tooth movement (OTM) is caused by an imbalance between the bone turnover rate and applied mechanical stress. The administration of 4-hexylresorcinol (4HR) increases the bone turnover rate and factors associated with bone formation. Thus, 4HR may show protective activity against root resorption during orthodontic tooth movement (OTM). A total of 40 rats (male: 20; female: 20) were included in this study, and the mandibular first molar was subjected to excessive orthodontic force. The experimental group (n = 20) received 12.8 mg/kg of 4HR every 2 weeks. The controls (n = 20) received a solvent without 4HR. Both groups had the same sex distribution. On Day 28 after the initiation of OTM, all the animals were sacrificed for micro-computed tomography analysis, Western blot analysis, and immunohistochemistry. The ratios of the root length and root volume to the total volume were significantly higher in the experimental group compared to those in the control group (p < 0.05). The expression levels of OPG, RANKL, alkaline phosphatase, and Runx2 in the experimental group according to Western blotting were significantly higher in the experimental group compared to those in the control group (p < 0.05). Their expression was mainly found in the periodontal ligament area. In conclusion, the administration of 4HR decreased the root resorption caused by OTM and increased the expression levels of OPG, RANKL, alkaline phosphatase, and Runx2. Full article

(This article belongs to the Special Issue Immunomodulation and Smart Materials for the Application of Maxillofacial Surgery)

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11 pages, 1777 KiB

Open AccessArticle

4-Hexylresorcinol Administration Increases Dental Hard Tissue Formation and Incisor Eruption Rate in Rats

by Ji-Hwan Kim, Dae-Won Kim, Seong-Gon Kim and Tae-Woo Kim

Appl. Sci. 2020, 10(16), 5511; https://doi.org/10.3390/app10165511 - 10 Aug 2020

Cited by 6 | Viewed by 1799

Abstract

Dental hard tissue formation and bone turnover are required for tooth eruption. 4-Hexylresorcinol (4HR) accelerates tooth movement by increasing bone turnover in orthodontic treatment. This study aimed to evaluate the following: (1) the effect of 4HR application on the expression of proteins associated with tooth formation, and (2) the effect of 4HR application on mandibular incisor eruption rate in a rat model. Primary cultured pulp cells received either 4HR (1 to 100 µM) or solvent only; western blotting was performed for transforming growth factor-beta 1 (TGF-β1), bone morphogenic protein-2/4 (BMP-2/4), runt-related transcription factor 2 (Runx2), osterix (OSX), dentin sialophosphoprotein (DSPP), and parathyroid hormone-related protein receptor (PTHrP-R). In in vivo study, rats (15 males and 15 females) received either solvent or 0.128 mg/kg or 12.8 mg/kg of 4HR via subcutaneous injection; mandibular incisor eruption rate was subsequently recorded. Immunohistochemical staining and western blotting for TGF-β1, BMP-2/4, Runx2, OSX, DSPP, and PTHrP-R were performed in the mandibular tissue samples. 4HR administration was found to increase TGF-β1, BMP-2/4, Runx2, OSX, DSPP, and PTHrP-R expression in both cell culture and tissue samples. Immunohistochemical staining of some markers showed site-specific expression, thereby indicating programmed differentiation of odontoblasts and ameloblasts. The eruption rate was significantly higher in the 12.8 mg/kg 4HR-administered group than in the untreated control (p = 0.001 and 0.010 for males and females, respectively). Collectively, 4HR administration increased the expression of markers related to dental hard tissue formation and accelerated the eruption rate of incisors in rats. Full article

(This article belongs to the Special Issue Immunomodulation and Smart Materials for the Application of Maxillofacial Surgery)

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9 pages, 2672 KiB

Open AccessArticle

Three-Dimensional Evaluation of Slow Maxillary Expansion with Leaf Expander vs. Rapid Maxillary Expansion in a Sample of Growing Patients: Direct Effects on Maxillary Arch and Spontaneous Mandibular Response

by Gianguido Cossellu, Alessandro Ugolini, Matteo Beretta, Marco Farronato, Alessandro Gianolio, Cinzia Maspero and Valentina Lanteri

Appl. Sci. 2020, 10(13), 4512; https://doi.org/10.3390/app10134512 - 29 Jun 2020

Cited by 9 | Viewed by 2544

Abstract

The aim is to evaluate the effects of slow maxillary expansion on maxillary and mandibular arch, using a slow maxillary expander (SME-Leaf Expander) banded on primary second molar. Ninety patients with transverse maxillary deficiency and posterior crossbite were selected. Sixty-nine patients (33 males/36 females; 7.6 ± 1.7 years old) who underwent SME and 21 patients (10 males/11 females; 7.4 ± 1.2 years old) who were treated with rapid maxillary expander (RME). Digital models obtained pre- and post-treatment at appliance removal (9 to 11 months) were processed by means of a 3D scanner (Trios 3, 3Shape D250 laser, Copenhagen, Denmark). Interdental width in both maxilla and mandible were measured with 3 SHAPE Ortho Analyzer. Four Maxillary and four mandibular interdental width were traced and evaluated. The adequate Student’s t-test (dependent or independent) was used to compare intra and intergroups interdental width differences (p < 0.05). The efficacy of the SME was confirmed both on maxillary and mandibular arch. All the maxillary and mandibular interdental widths increased significantly (p < 0.001). The comparison with the RME group showed significant statistical differences between the two treatments with a greater increase in primary first and second intermolar and canine width for the test group (p < 0.001). SME with Leaf Expander produced statistically significant effects for the correction of transverse maxillary deficiencies with a significant indirect effect on the mandibular arch. Full article

(This article belongs to the Special Issue Immunomodulation and Smart Materials for the Application of Maxillofacial Surgery)

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9 pages, 8810 KiB

Open AccessArticle

Effect of Ultraviolet Irradiation on Osseointegration of Dental Implants: A Comparative Histomorphometric Study in Canine Models

by Chunui Lee, Seung-Mi Jeong, Hyun-Woo Yang and Byung-Ho Choi

Appl. Sci. 2020, 10(12), 4216; https://doi.org/10.3390/app10124216 - 19 Jun 2020

Cited by 4 | Viewed by 2761

Abstract

Recent studies have focused on achieving sound osseointegration applying methods of surface reprocessing of dental implants using ultraviolet (UV) irradiation. However, there have been few reports on the effect of UV irradiation on osseointegration in both the short and long term, and experimental studies using the canine model do not exist. Therefore, the aim of this study was to determine the short- and long-term degree of osseointegration of dental implants according to UV irradiation using a histometric analysis in canine models. Four beagles were used for this study and 24 dental implants were placed. Six implants were inserted with flapless protocols in each mandible. Half of the implants were UV-irradiated prior to implantation. UV-treated and untreated implants were placed one after the other; implant stability was recorded using the implant stability test (IST) immediately after implantation and every seven days thereafter. Two of the beagles were sacrificed after four weeks and the other two after 12 weeks. The implants were removed in block sections and were evaluated histomorphologically and statistically. As a result, we found no statistically significant differences in the mean IST values and in bone-to-implant contact (BIC) in all groups at 4 and 12 weeks. Full article

(This article belongs to the Special Issue Immunomodulation and Smart Materials for the Application of Maxillofacial Surgery)

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11 pages, 2101 KiB

Open AccessArticle

Bone Regeneration in Peri-Implant Defect Using Autogenous Tooth Biomaterial Enriched with Platelet-Rich Fibrin in Animal Model

by Moon Hwan Jung, Jeong Hun Lee, Puneet Wadhwa, Heng Bo Jiang, Hyon Seok Jang and Eui Seok Lee

Appl. Sci. 2020, 10(6), 1939; https://doi.org/10.3390/app10061939 - 12 Mar 2020

Cited by 10 | Viewed by 3108

Abstract

Tooth biomaterial may be useful in bone regeneration for restoring peri-implant defects in vivo. The aim of this study was to compare bone regeneration capacity in peri-implant defects augmented with autogenous tooth biomaterial combined with platelet-rich fibrin (PRF), tooth biomaterial alone, or PRF alone. Two monocortical defects were generated on each tibia of 10 New Zealand white rabbits (n = 10 per group) with a trephine bur, and the dental implant was installed into the defects. In experimental groups 1, 2, and 3, the peri-implant defects were filled with tooth biomaterial and platelet-rich fibrin (PRF), tooth biomaterial only, and PRF only, respectively and the control was left empty. Micro computed tomography (CT), implant stability, and histomorphometric analysis were conducted eight weeks after operation. The mean regenerated bone areas were 53.87 ± 7.60%, 51.56 ± 6.45%, and 18.45 ± 1.34% in experimental groups 1, 2, and 3, respectively, and 11.57 ± 1.12% in the control. Mean bone-to-implant contact values were 43.67 ± 2.50%, 41.07 ± 2.59%, and 21.45 ± 1.25% in experimental groups 1, 2, and 3, respectively, and 16.57 ± 2.83% in the control. Tooth biomaterial enriched with platelet-rich fibrin (PRF) and tooth biomaterial alone showed more enhanced regeneration than PRF alone in our study. Full article

(This article belongs to the Special Issue Immunomodulation and Smart Materials for the Application of Maxillofacial Surgery)

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11 pages, 2101 KiB

Open AccessFeature PaperArticle

4-Hexylresorcinol Exhibits Different Characteristics to Estrogen

by Yei-Jin Kang, Ji-Hyeon Oh, Hyun Seok, You-Young Jo, Dae-Won Kim, Umberto Garagiola, Je-Yong Choi and Seong-Gon Kim

Appl. Sci. 2020, 10(5), 1737; https://doi.org/10.3390/app10051737 - 03 Mar 2020

Cited by 10 | Viewed by 2828

Abstract

4-Hexylresorcinol (4HR) has been used as a food additive and antiseptic. The aim of this study was to evaluate whether the application of 4HR in breast cancer cells and ovariectomized rats showed estrogen-like effects. MCF-7 and SK-BR-3 cells were treated by solvent, 1–100 µM bisphenol-A (BPA), or 1–100 µM 4HR, respectively. 3-(4, 5-Dimethylthiazole-2-yl)- 2,5-diphenyltetrazolium bromide (MTT) assay and Western blot for extracellular signal-regulated kinase-1/-2 (ERK1/2), phosphorylated ERK1/2 (p-ERK1/2), estrogen receptor-α (ERα), and ERβ were done. As an in vivo study, ovariectomized rats (n = 15) received solvent, 125 mg/kg of 4HR, or 10 µg of 17-β estradiol via daily subcutaneous injection for 7 days. Blood samples were obtained for evaluation of prolactin levels. Pituitary glands and uteruses were biopsied for histological evaluation and Western blot analysis. Compared with the control group, the application of 4HR decreased the proliferation of MCF-7 and SK-BR-3 cells, while the application of BPA increased (p < 0.05). The application of BPA increased the expression of ERα, ERβ, and p-ERK1/2, but 4HR did not change the expression of ERα, ERβ, or p-ERK1/2 in MCF-7 cells. In an animal model, the 4HR group showed similar levels of ERα, ERβ, and prolactin expression in the pituitary gland compared to the solvent only group, while the estradiol group showed higher levels. Serum prolactin levels were similar between the 4HR and solvent only groups. Taken together, 1–100 µM 4HR did not show BPA-like behavior in MCF-7 cells, and 125 mg/kg of 4HR daily subcutaneous injection for 7 days did not demonstrate estradiol-like effects in ovariectomized rats. Collectively, 4HR has no estrogen-like effects on both ERα-positive cells and estrogen-deficient rat models. Full article

(This article belongs to the Special Issue Immunomodulation and Smart Materials for the Application of Maxillofacial Surgery)

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Review

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17 pages, 3325 KiB

Open AccessReview

Sericin for Tissue Engineering

by You-Young Jo, HaeYong Kweon and Ji-Hyeon Oh

Appl. Sci. 2020, 10(23), 8457; https://doi.org/10.3390/app10238457 - 27 Nov 2020

Cited by 20 | Viewed by 3961

Abstract

Sericin is a 10-to-400 kDa hydrophilic protein with high serine content and is a silk constituent together with fibroin. It is produced in the middle silk gland of the silkworm and encoded by four sericin genes. The molecular weight of sericin and its biological activity vary depending on the extraction method employed. Its chemical structure, in terms of random coil and β-sheet conformations, also differs with the extraction method, thereby extending its applications in various fields. Sericin, which was discarded in the textile industry in the past, is being applied and developed in the biomedical field, owing to its biological properties. In particular, many studies are underway in the field of tissue engineering, evaluating its applicability in burn dressing, drug delivery, bone regeneration, cartilage regeneration, and nerve regeneration. Full article

(This article belongs to the Special Issue Immunomodulation and Smart Materials for the Application of Maxillofacial Surgery)

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11 pages, 3005 KiB

Open AccessReview

Role of 4-Hexylresorcinol in the Field of Tissue Engineering

by Jwa-Young Kim and Hyun Seok

Appl. Sci. 2020, 10(10), 3385; https://doi.org/10.3390/app10103385 - 14 May 2020

Cited by 8 | Viewed by 2474

Abstract

4-hexylresorcinol (4-HR), as a derivative of phenolic lipids, has biological and pharmacological properties that are beneficial when used with a biomaterial. It has antimicrobial and antiseptic activity and can thus prevent contamination and infection of biomaterials. 4-HR suppresses the nuclear factor kappa B (NF-κB) signaling pathway related to osteoclast differentiation. The suppression of NF-κB increases the bone formation marker and contributes to new bone formation. The tumor necrosis factor-α (TNF-α) is a pro-inflammatory cytokine produced by macrophages and suppressed by 4-HR. Suppression of TNF-α decreases osteoclast activity and promotes wound healing. 4-HR increases the vascular endothelial growth factor and has an anti-thrombotic effect. When incorporated into silk vascular patches, it promotes endothelium wound healing. Recently, 4-HR has exhibited biological properties and has been successfully incorporated into various biomaterials. Consequently, it is a useful pharmacological chemical that can be used with biomaterials in the field of tissue engineering. Full article

(This article belongs to the Special Issue Immunomodulation and Smart Materials for the Application of Maxillofacial Surgery)

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