• Journal of Periodontal and Implant Science
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• 제43권6호
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• pp.251-261
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• 2013

A paradigm shift is taking place in medicine and dentistry from using synthetic implants and tissue grafts to a tissue engineering approach that uses degradable porous three-dimensional (3D) material hydrogels integrated with cells and bioactive factors to regenerate tissues such as dental bone and other oral tissues. Hydrogels have been established as a biomaterial of choice for many years, as they offer diverse properties that make them ideal in regenerative medicine, including dental applications. Being highly biocompatible and similar to native extracellular matrix, hydrogels have emerged as ideal candidates in the design of 3D scaffolds for tissue regeneration and drug delivery applications. However, precise control over hydrogel properties, such as porosity, pore size, and pore interconnectivity, remains a challenge. Traditional techniques for creating conventional crosslinked polymers have demonstrated limited success in the formation of hydrogels with large pore size, thus limiting cellular infiltration, tissue ingrowth, vascularization, and matrix mineralization (in the case of bone) of tissue-engineered constructs. Emerging technologies have demonstrated the ability to control microarchitectural features in hydrogels such as the creation of large pore size, porosity, and pore interconnectivity, thus allowing the creation of engineered hydrogel scaffolds with a structure and function closely mimicking native tissues. In this review, we explore the various technologies available for the preparation of macroporous scaffolds and their potential applications.

• Tissue Engineering and Regenerative Medicine
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• 제15권6호
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• pp.781-791
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• 2018

BACKGROUND: Glucosamine hydrochloride (GlcN HCl) has been shown to inhibit cell growth and matrix synthesis, but not with N-acetyl-glucosamine (GlcNAc) supplementation. This effect might be related to an inhibition of critical growth factors (GF), or to a different metabolization of the two glucosamine derivatives. The aim of the present study was to evaluate the synergy between GlcN HCl, GlcNAc, and GF on proliferation and cartilage matrix synthesis. METHOD: Bovine chondrocytes were cultivated in monolayers for 48 h and in three-dimensional (3D) chitosan scaffolds for 30 days in perfusion bioreactors. Serum-free (SF) medium was supplemented with either growth factors (GF) $TGF-{\beta}$ ($5ng\;mL^{-1}$) and IGF-I ($10ng\;mL^{-1}$), GlcN HCl or GlcNAc at 1mM each or both. Six groups were compared according to medium supplementation: (a) SF control; (b) SF + GlcN HCl; (c) SF + GlcNAc; (d) SF + GF; (e) SF + GF + GlcN HCl; and (f) SF + GF + GlcNAc. Cell proliferation, proteoglycan, collagen I (COL1), and collagen II (COL2) synthesis were evaluated. RESULTS: The two glucosamines showed opposite effects in monolayer culture: GlcN HCl significantly reduced proliferation and GlcNAc significantly augmented cellular metabolism. In the 30 days 3D culture, the GlcN HCl added to GF stimulated cell proliferation more than when compared to GF only, but the proteoglycan synthesis was smaller than GF. However, GlcNAc added to GF improved the cell proliferation and proteoglycan synthesis more than when compared to GF and GF/GlcN HCl. The synthesis of COL1 and COL2 was observed in all groups containing GF. CONCLUSION: GlcN HCl and GlcNAc increased cell growth and stimulated COL2 synthesis in long-time 3D culture. However, only GlcNAc added to GF improved proteoglycan synthesis.

• BMB Reports
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• 제49권12호
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• pp.655-661
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• 2016

Polymer brush is a soft material unit tethered covalently on the surface of scaffolds. It can induce functional and structural modification of a substrate's properties. Such surface coating approach has attracted special attentions in the fields of stem cell biology, tissue engineering, and regenerative medicine due to facile fabrication, usability of various polymers, extracellular matrix (ECM)-like structural features, and in vivo stability. Here, we summarized polymer brush-based grafting approaches comparing self-assembled monolayer (SAM)-based coating method, in addition to physico-chemical characterization techniques for surfaces such as wettability, stiffness/elasticity, roughness, and chemical composition that can affect cell adhesion, differentiation, and proliferation. We also reviewed recent advancements in cell biological applications of polymer brushes by focusing on stem cell differentiation and 3D supports/implants for tissue formation. Understanding cell behaviors on polymer brushes in the scale of nanometer length can contribute to systematic understandings of cellular responses at the interface of polymers and scaffolds and their simultaneous effects on cell behaviors for promising platform designs.

• Medical Lasers
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• 제9권1호
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• pp.6-11
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• 2020

Hydrogels have been developed and used in tissue engineering and regenerative medicine to deliver therapeutics to injured or diseased tissue because of their versatility and properties that can be tailored to match the natural extracellular matrix. Hydrogels can be made with a variety of physical and chemical properties combined with light responsiveness ideal for applications in different fields of medicine that require the spatiotemporal control of therapeutics. Light, as a stimulus, is relatively inexpensive, contact-free, noninvasive with high spatial resolution and temporal control, convenient and easy to use, and allows deep tissue penetration that is relatively harmless. Photoresponsive hydrogels are ideal candidates for on-demand drug delivery systems that are capable of sustained and controlled drug release, minimizing the side effects, and ensuring the activity and efficient delivery of drugs to the target tissue.

• International Journal of Industrial Entomology and Biomaterials
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• 제48권1호
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• pp.1-12
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• 2024

Silk sericin, a natural protein from silkworm cocoons, is emerging as a multifunctional biomaterial in biomedicine, particularly in tissue engineering and wound healing. Recent studies have highlighted its biocompatibility, biodegradability, and potential for chemical modification, which allows it to be incorporated into various scaffold architectures. This review article synthesizes current research, including the development of sericin-based hydrogel scaffolds for tissue engineering and sericin's role in enhancing wound healing. Key findings demonstrate sericin's ability to refine scaffold porosity and mechanical strength, expedite tissue healing, and reduce bacterial load in wounds. The integration of sericin into novel bioactive dressings and its use in peripheral nerve injury repair are also discussed, showcasing its adaptability and efficacy. The convergence of these studies illustrates the broad applications of sericin, from scaffold design to clinical interventions, making it a promising material in regenerative medicine and tissue engineering, with the potential to improve patient outcomes significantly.

• Tissue Engineering and Regenerative Medicine
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• 제15권6호
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• pp.711-719
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• 2018

BACKGROUND: Collagen organization within tissues has a critical role in wound regeneration. Collagen fibril diameter, arrangements and maturity between connective tissue growth factor (CTGF) small interfering RNA (siRNA) and mismatch scrambled siRNA-treated wound were compared to evaluate the efficacy of CTGF siRNA as a future implement for scar preventive medicine. METHODS: Nanocomplexes of CTGF small interfering RNA (CTGF siRNA) with cell penetrating peptides (KALA and $MPG^{{\Delta}NLS}$) were formulated and their effects on CTGF downregulation, collagen fibril diameter and arrangement were investigated. Various ratios of CTGF siRNA and peptide complexes were prepared and down-regulation were evaluated by immunoblot analysis. Control and CTGF siRNA modified cells-populated collagen lattices were prepared and rates of contraction measured. Collagen organization in rabbit ear 8 mm biopsy punch wound at 1 day to 8 wks post injury time were investigated by transmission electron microscopy and histology was investigated with Olympus System and TS-Auto software. CONCLUSION: CTGF expression was down-regulated to 40% of control by CTGF siRNA/KALA (1:24) complexes (p<0.01) and collagen lattice contraction was inhibited. However, down-regulated of CTGF by CTGF $siRNA/MPG^{{\Delta}NLS}$ complexes was not statistically significant. CTGF KALA-treated wound appeared with well formed-basket weave pattern of collagen fibrils with mean diameter of $128{\pm}22nm$ (n = 821). Mismatch siRNA/KALA-treated wound showed a high frequency of parallel small diameter fibrils (mean $90{\pm}20nm$, n = 563). CONCLUSION: Controlling over-expression of CTGF by peptide-mediated siRNA delivery could improve the collagen orientation and tissue remodeling in full thickness rabbit ear wound.

• Journal of Periodontal and Implant Science
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• 제47권6호
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• pp.363-371
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• 2017

Purpose: The purpose of this study was to investigate the feasibility of regenerative therapy with a collagenated bone graft and resorbable membrane in intrabony defects, and to evaluate the effects of the novel extracellular matrix (ECM)-based membrane clinically and radiologically. Methods: Periodontal tissue regeneration procedure was performed using an ECM-based resorbable membrane in combination with a collagenated bovine bone graft in intrabony defects around the teeth and implants. A novel extracellular matrix membrane (NEM) and a widely-used membrane (WEM) were randomly applied to the test group and the control group, respectively. Cone-beam computed tomography images were obtained on the day of surgery and 6 months after the procedure. Alginate impressions were taken and plaster models were made 1 week and 6 months postoperatively. Results: The quantity of bone tissue, the dimensional changes of the surgically treated intrabony defects, and the changes in width and height below the grafted bone substitutes showed no significant difference between the test and control groups at the 6-month examination. Conclusions: The use of NEM for periodontal regeneration with a collagenated bovine bone graft showed similar clinical and radiologic results to those obtained using WEM.

• 대한치과보철학회지
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• 제32권4호
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• pp.593-607
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• 1994

The purpose of this study is to evaluate the effect of the bone morphogenetic protein, bone matrix gelatin and collagen matrix on the amount and shape of generating new bone adjacent to the implant. Implants were inserted in the mandible of adult dogs at 2 months after teeth extraction. Artificial bony defects, 3mm in width and 4mm in depth were made at the mesial and distal side of implant. Experimental groups were divided into three groups ; Group 1 : Defects filled with collagen matrix and bone morphogenetic protein, Group 2 : Defects filled with bone matrix gelatin. Control group : Defects filled with only collagen matrix. After implantation, the animals were sacrificed at 1,3,5 and 10 weeks for light microscopic examination. For the fluorescent microscopic examination. each tertracycline Hcl and calcein were injected at 1, 3, 5, 8 and 10 weeks after implantation. The results obtained were as follows : 1. The molecular weight of bovine BMP was about 18,100 by hydroxyapatite chromatography. 2. Osseointegration was observed in experimental groups 1 & 2, and BMG and BMP had an excellent bone forming capability as a filling materials to the repair of the bone defects. 3. The degree of healing of bone defect area, the experimental group 1 showed more prominent bone formation than control group, and the control group showed fibrous connective tissue between the implant and the bone. 4. In the fluorescent microscopic findings, bone remodelling was observed regenerative lamellar bone at defect area in experimental group 1, and partial remodelling in experimental group 2, In the control group, fibrous connective tissue was observed between the implant and bone surface and sign of remodelling was not apperaed. Above results suggest that BMP has rapid osteoinductive property and can be used clinically as a bone substitute on bone defects around implants.

• Tissue Engineering and Regenerative Medicine
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• 제15권6호
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• pp.721-733
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• 2018

BACKGROUND: Because three-dimensional (3D) models more closely mimic native tissues, one of the goals of 3D in vitro tissue models is to aid in the development and toxicity screening of new drug therapies. In this study, a 3D skin wound healing model comprising of a collagen type I construct with fibrin-filled defects was developed. METHODS: Optical imaging was used to measure keratinocyte migration in the presence of fibroblasts over 7 days onto the fibrin-filled defects. Additionally, cell viability and growth of fibroblasts and keratinocytes was measured using the $alamarBlue^{(R)}$ assay and changes in the mechanical stiffness of the 3D construct was monitored using compressive indentation testing. RESULTS: Keratinocyte migration rate was significantly increased in the presence of fibroblasts with the cells reaching the center of the defect as early as day 3 in the co-culture constructs compared to day 7 for the control keratinocyte monoculture constructs. Additionally, constructs with the greatest rate of keratinocyte migration had reduced cell growth. When fibroblasts were cultured alone in the wound healing construct, there was a 1.3 to 3.4-fold increase in cell growth and a 1.2 to 1.4-fold increase in cell growth for keratinocyte monocultures. However, co-culture constructs exhibited no significant growth over 7 days. Finally, mechanical testing showed that fibroblasts and keratinocytes had varying effects on matrix stiffness with fibroblasts degrading the constructs while keratinocytes increased the construct's stiffness. CONCLUSION: This 3D in vitro wound healing model is a step towards developing a mimetic construct that recapitulates the complex microenvironment of healing wounds and could aid in the early studies of novel therapeutics that promote migration and proliferation of epithelial cells.

• Journal of Korean Dental Science
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• 제17권2호
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• pp.53-63
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• 2024

Purpose: To investigate the effects of simultaneous soft and hard tissue augmentation and the addition of polydeoxyribonucleotide (PDRN) on regenerative outcomes. Materials and Methods: In five mongrel dogs, chronic ridge defects were established in both mandibles. Six implants were placed in the mandible, producing buccal dehiscence defects. The implants were randomly allocated to one of the following groups: 1) control: no treatment; 2) GBR: guided bone regeneration (GBR) only; 3) GBR/PDRN: GBR+PDRN application to bone substitute particles; 4) GBR/CTG: GBR+connective tissue grafting (CTG); 5) GBR/VCMX: GBR+soft tissue augmentation using volume stable collagen matrix (VCMX); and 6) group GBR/VCMX/PDRN: GBR+VCMX soaked with PDRN. The healing abutments were connected to the implants to provide additional room for tissue regeneration. Submerged healing was achieved. The animals were euthanized after four months. Histological and histomorphometric analyses were then performed. Results: Healing abutments were gradually exposed during the healing period. Histologically, minimal new bone formation was observed in the dehiscence defects. No specific differences were found between the groups regarding collagen fiber orientation and density in the augmented area. No traces of CTG or VCMX were detected. Histomorphometrically, the mean tissue thickness was greater in the control group than in the other groups above the implant shoulder (IS). Below the IS level, the CTG and PDRN groups exhibited more favorable tissue thickness than the other groups. Conclusion: Failure of submerged healing after tissue augmentation deteriorated the tissue contour. PDRN appears to have a positive effect on soft tissues.