The Experts below are selected from a list of 360 Experts worldwide ranked by ideXlab platform
Kazunori Yasuda - One of the best experts on this subject based on the ideXlab platform.
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effects of Osteochondral Defect size on cartilage regeneration using a double network hydrogel
BMC Musculoskeletal Disorders, 2017Co-Authors: Nobuto Kitamura, Fuminori Kanaya, Takayuki Kurokawa, Jian Ping Gong, Kotaro Higa, Keiko Goto, Kazunori YasudaAbstract:There has been increased interest in one-step cell-free procedures to avoid the problems related to cell manipulation and its inherent disadvantages. We have studied the chondrogenic induction ability of a PAMPS/PDMAAm double-network (DN) gel and found it to induce chondrogenesis in animal Osteochondral Defect models. The purpose of this study was to investigate whether the healing process and the degree of cartilage regeneration induced by the cell-free method using DN gel are influenced by the size of Osteochondral Defects. A total of 63 mature female Japanese white rabbits were used in this study, randomly divided into 3 groups of 21 rabbits each. A 2.5-mm diameter Osteochondral Defect was created in the femoral trochlea of the patellofemoral joint of bilateral knees in Group I, a 4.3-mm Osteochondral Defect in Group II, and a 5.8-mm Osteochondral Defect in Group III. In the right knee of each animal, a DN gel plug was implanted so that a vacant space of 2-mm depth was left above the plug. In the left knee, we did not conduct any treatment to obtain control data. Animals were sacrificed at 2, 4, and 12 weeks after surgery, and gross and histological evaluations were made. The present study demonstrated that all sizes of the DN gel implanted Defects as well as the 2.5mm untreated Defects showed cartilage regeneration at 4 and 12 weeks. The 4.3-mm and 5.8-mm untreated Defects did not show cartilage regeneration during the 12-week period. The quantitative score reported by O’Driscoll et al. was significantly higher in the 4.3-mm and 5.8-mm DN gel-implanted Defects than the untreated Defects at 4 and 12 weeks (p < 0.05). The 2.5-mm and 4.3-mm DN gel implanted Defects maintained relatively high macroscopic and histological scores for the 12-week implantation period, while the histological score of the 5.8-mm DN gel implanted Defect had decreased somewhat but statistically significantly at 12 weeks (p = 0.0057). The DN gel induced cartilage regeneration in Defects between 2.5 and 5.8 mm, offering a promising device to establish a cell-free cartilage regeneration therapy and applicable to various sizes of Osteochondral Defects.
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hydroxyapatite coated double network hydrogel directly bondable to the bone biological and biomechanical evaluations of the bonding property in an Osteochondral Defect
Acta Biomaterialia, 2016Co-Authors: Susumu Wada, Nobuto Kitamura, Takayuki Kurokawa, Jian Ping Gong, Takayuki Nonoyama, Ryuji Kiyama, Kazunori YasudaAbstract:Abstract We have developed a novel hydroxyapatite (HAp)-coated double-network (DN) hydrogel (HAp/DN gel). The purpose of this study was to determine details of the cell and tissue responses around the implanted HAp/DN gel and to determine how quickly and strongly the HAp/DN gel bonds to the bone in a rabbit Osteochondral Defect model. Immature osteoid tissue was formed in the space between the HAp/DN gel and the bone at 2 weeks, and the osteoid tissue was mineralized at 4 weeks. The push-out load of the HAp/DN gel averaged 37.54 N and 42.15 N at 4 and 12 weeks, respectively, while the push-out load of the DN gel averaged less than 5 N. The bonding area of the HAp/DN gel to the bone was above 80% by 4 weeks, and above 90% at 12 weeks. This study demonstrated that the HAp/DN gel enhanced osseointegration at an early stage after implantation. The presence of nanoscale structures in addition to osseointegration of HAp promoted osteoblast adhesion onto the surface of the HAp/DN gel. The HAp/DN gel has the potential to improve the implant-tissue interface in next-generation orthopaedic implants such as artificial cartilage. Statement of Significance Recent studies have reported the development of various hydrogels that are sufficiently tough for application as soft supporting tissues. However, fixation of hydrogels on bone surfaces with appropriate strength is a great challenge. We have developed a novel, tough hydrogel hybridizing hydroxyapatite (HAp/DN gel), which is directly bondable to the bone. The present study demonstrated that the HAp/DN gel enhanced osseointegration in the early stage after implantation. The presence of nanoscale structures in addition to the osseointegration ability of hydroxyapatite promoted osteoblast adhesion onto the surface of the HAp/DN gel. The HAp/DN gel has the potential to improve the implant-tissue interface in next-generation orthopaedic implants such as artificial cartilage.
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intra articular administration of hyaluronic acid increases the volume of the hyaline cartilage regenerated in a large Osteochondral Defect by implantation of a double network gel
Journal of Materials Science: Materials in Medicine, 2014Co-Authors: Takaaki Fukui, Nobuto Kitamura, Takayuki Kurokawa, Jian Ping Gong, Masashi Yokota, Eiji Kondo, Kazunori YasudaAbstract:Implantation of PAMPS/PDMAAm double-network (DN) gel can induce hyaline cartilage regeneration in the Osteochondral Defect. However, it is a problem that the volume of the regenerated cartilage tissue is gradually reduced at 12 weeks. This study investigated whether intra-articular administration of hyaluronic acid (HA) increases the volume of the cartilage regenerated with the DN gel at 12 weeks. A total of 48 rabbits were used in this study. A cylindrical Osteochondral Defect created in the bilateral femoral trochlea was treated with DN gel (Group DN) or left without any implantation (Group C). In both Groups, we injected 1.0 mL of HA in the left knee, and 1.0 mL of saline solution in the right knee. Quantitative histological evaluations were performed at 2, 4, and 12 weeks, and PCR analysis was performed at 2 and 4 weeks after surgery. In Group DN, the proteoglycan-rich area was significantly greater in the HA-injected knees than in the saline-injected knees at 12 weeks (P = 0.0247), and expression of type 2 collagen, aggrecan, and Sox9 mRNAs was significantly greater in the HA-injected knees than in the saline-injected knees at 2 weeks (P = 0.0475, P = 0.0257, P = 0.0222, respectively). The intra-articular administration of HA significantly enhanced these gene expression at 2 weeks and significantly increased the volume of the hyaline cartilage regenerated by implantation of a DN gel at 12 weeks. This information is important to develop an additional method to increase the volume of the hyaline cartilage tissue in a potential cartilage regeneration strategy using the DN gel.
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influence of the gel thickness on in vivo hyaline cartilage regeneration induced by double network gel implanted at the bottom of a large Osteochondral Defect short term results
BMC Musculoskeletal Disorders, 2013Co-Authors: Kazunobu Arakaki, Nobuto Kitamura, Hidetoshi Matsuda, Fuminori Kanaya, Takayuki Kurokawa, Jian Ping Gong, Kazunori YasudaAbstract:Background A double-network (DN) gel, which is composed of poly(2-acrylamido-2-methylpropanesulfonic acid) and poly(N,N’-dimethyl acrylamide), can induce hyaline cartilage regeneration in vivo in a large Osteochondral Defect. The purpose of this study was to clarify the influence of the thickness of the implanted DN gel on the induction ability of hyaline cartilage regeneration.
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influence of the gel thickness on in vivo hyaline cartilage regeneration induced by double network gel implanted at the bottom of a large Osteochondral Defect short term results
BMC Musculoskeletal Disorders, 2013Co-Authors: Kazunobu Arakaki, Nobuto Kitamura, Hidetoshi Matsuda, Fuminori Kanaya, Takayuki Kurokawa, Jian Ping Gong, Kazunori YasudaAbstract:A double-network (DN) gel, which is composed of poly(2-acrylamido-2-methylpropanesulfonic acid) and poly(N,N’-dimethyl acrylamide), can induce hyaline cartilage regeneration in vivo in a large Osteochondral Defect. The purpose of this study was to clarify the influence of the thickness of the implanted DN gel on the induction ability of hyaline cartilage regeneration. Thirty-eight mature rabbits were used in this study. We created an Osteochondral Defect having a diameter of 4.3-mm in the patellofemoral joint. The knees were randomly divided into 4 groups (Group I: 0.5-mm thick gel, Group II: 1.0-mm thick gel, Group III: 5.0-mm thick gel, and Group IV: untreated control). Animals in each group were further divided into 3 sub-groups depending on the gel implant position (2.0-, 3.0-, or 4.0-mm depth from the articular surface) in the Defect. The regenerated tissues were evaluated with the Wayne’s gross and histological grading scales and real time PCR analysis of the cartilage marker genes at 4 weeks. According to the total Wayne’s score, when the depth of the final vacant space was set at 2.0 mm, the scores in Groups I, II, and III were significantly greater than that Group IV (p < 0.05), although there were no significant differences between Groups I and IV at a 3.0-mm deep vacant space. The expression levels of type-2 collagen in Groups II and III were significantly higher (p < 0.05) than that in Group IV. The 1.0-mm thick DN gel sheet had the same ability to induce hyaline cartilage regeneration as the 5.0-mm thick DN gel plug. However, the induction ability of the 0.5-mm thick sheet was significantly lower when compared with the 1.0-mm thick gel sheet. The 1.0-mm DN gel sheet is a promising device to establish a cell-free cartilage regeneration strategy that minimizes bone loss from the gel implantation.
Hu Zhang - One of the best experts on this subject based on the ideXlab platform.
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allogeneic primary mesenchymal stem stromal cell aggregates within poly n isopropylacrylamide co acrylic acid hydrogel for Osteochondral regeneration
Applied Materials Today, 2020Co-Authors: Jiabin Zhang, Liming Wang, Hu Zhang, Ming Zhang, Rongcai Lin, Seonho Yun, Qingqiang Yao, Andrew C W ZannettinoAbstract:Abstract Osteoarthritis (OA) is an inflammation-related chronic disease that causes progressive degeneration of cartilage, which might even extend to subchondral bones. Due to the unique physiological structural differences between cartilage and subchondral bone, it is challenging to restore the full function of an Osteochondral Defect. In this study, a thermosensitive poly(N-isopropylacrylamide-co-acrylic acid) (p(NIPAAm-AA)) hydrogel was used as a carrier for allogeneic primary mesenchymal stem/stromal cells to determine the therapeutic efficacy of the cell-hydrogel hybrid on Osteochondral regeneration. At a similar mechanical strength, p(NIPAAm-AA) hydrogel facilitates formation of cell aggregates of allogeneic primary MSCs in situ, while the fibrin hydrogel supports cell binding and the development of a spindle morphology. While the p(NIPAAm-AA) hydrogel did not induce any inflammatory effects, the fibrin hydrogel was found to elicit a pro-inflammatory response. MSC aggregates promotes expression of paracrine signaling-related genes (TGFB1, VEGF, CXCL12, IGF1, BMP2, BMP7, WNT3A, CTNNB1) as well as expression of chondrogenesis-related genes (SOX9, ACAN, and COL2A1) and generation of extracellular matrices (ECMs) (type 2 collagen and glycosaminoglycans) in chondrogenic induction medium. The functional enhancement of paracrine effects by MSC aggregates (i.e. the immunomodulatory effect and the stimulation of stem/progenitor cells homing) and induced differentiation of MSCs might play a synergistic role in the generation of the neo-cartilage and subchondral bone at an Osteochondral Defect site in vivo. Delivery of primary allogeneic MSCs in the context of a thermosensitive p(NIPAAm-AA) hydrogel to an Osteochondral Defect site may be a novel and promising strategy for Osteochondral regeneration.
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Allogeneic primary mesenchymal stem/stromal cell aggregates within poly(N-isopropylacrylamide-co-acrylic acid) hydrogel for Osteochondral regeneration
'Elsevier BV', 2020Co-Authors: Zhang Jiabin, Zhang Ming, Lin Rongcai, Yun Seonho, Du Yuguang, Wang Liming, Yao Qingqiang, Zannettino Andrew, Hu ZhangAbstract:Osteoarthritis (OA) is an inflammation-related chronic disease that causes progressive degeneration of cartilage, which might even extend to subchondral bones. Due to the unique physiological structural differences between cartilage and subchondral bone, it is challenging to restore the full function of an Osteochondral Defect. In this study, a thermosensitive poly(N-isopropylacrylamide-co-acrylic acid) (p(NIPAAm-AA)) hydrogel was used as a carrier for allogeneic primary mesenchymal stem/stromal cells to determine the therapeutic efficacy of the cell-hydrogel hybrid on Osteochondral regeneration. At a similar mechanical strength, p(NIPAAm-AA) hydrogel facilitates formation of cell aggregates of allogeneic primary MSCs in situ, while the fibrin hydrogel supports cell binding and the development of a spindle morphology. While the p(NIPAAm-AA) hydrogel did not induce any inflammatory effects, the fibrin hydrogel was found to elicit a pro-inflammatory response. MSC aggregates promotes expression of paracrine signaling-related genes (TGFB1, VEGF, CXCL12, IGF1, BMP2, BM137, WNT3A, CTNNB1) as well as expression of chondrogenesis-related genes (S0X9, ACAN, and COL2A1) and generation of extracellular matrices (ECMs) (type 2 collagen and glycosaminoglycans) in chondrogenic induction medium. The functional enhancement of paracrine effects by MSC aggregates (i.e. the immunomodulatory effect and the stimulation of stem/progenitor cells homing) and induced differentiation of MSCs might play a synergistic role in the generation of the neo-cartilage and subchondral bone at an Osteochondral Defect site in vivo. Delivery of primary allogeneic MSCs in the context of a thermosensitive p(NIPAAm-AA) hydrogel to an Osteochondral Defect site may be a novel and promising strategy for Osteochondral regeneration. (C) 2019 Elsevier Ltd. All rights reserved
Liming Wang - One of the best experts on this subject based on the ideXlab platform.
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allogeneic primary mesenchymal stem stromal cell aggregates within poly n isopropylacrylamide co acrylic acid hydrogel for Osteochondral regeneration
Applied Materials Today, 2020Co-Authors: Jiabin Zhang, Liming Wang, Hu Zhang, Ming Zhang, Rongcai Lin, Seonho Yun, Qingqiang Yao, Andrew C W ZannettinoAbstract:Abstract Osteoarthritis (OA) is an inflammation-related chronic disease that causes progressive degeneration of cartilage, which might even extend to subchondral bones. Due to the unique physiological structural differences between cartilage and subchondral bone, it is challenging to restore the full function of an Osteochondral Defect. In this study, a thermosensitive poly(N-isopropylacrylamide-co-acrylic acid) (p(NIPAAm-AA)) hydrogel was used as a carrier for allogeneic primary mesenchymal stem/stromal cells to determine the therapeutic efficacy of the cell-hydrogel hybrid on Osteochondral regeneration. At a similar mechanical strength, p(NIPAAm-AA) hydrogel facilitates formation of cell aggregates of allogeneic primary MSCs in situ, while the fibrin hydrogel supports cell binding and the development of a spindle morphology. While the p(NIPAAm-AA) hydrogel did not induce any inflammatory effects, the fibrin hydrogel was found to elicit a pro-inflammatory response. MSC aggregates promotes expression of paracrine signaling-related genes (TGFB1, VEGF, CXCL12, IGF1, BMP2, BMP7, WNT3A, CTNNB1) as well as expression of chondrogenesis-related genes (SOX9, ACAN, and COL2A1) and generation of extracellular matrices (ECMs) (type 2 collagen and glycosaminoglycans) in chondrogenic induction medium. The functional enhancement of paracrine effects by MSC aggregates (i.e. the immunomodulatory effect and the stimulation of stem/progenitor cells homing) and induced differentiation of MSCs might play a synergistic role in the generation of the neo-cartilage and subchondral bone at an Osteochondral Defect site in vivo. Delivery of primary allogeneic MSCs in the context of a thermosensitive p(NIPAAm-AA) hydrogel to an Osteochondral Defect site may be a novel and promising strategy for Osteochondral regeneration.
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bioactive scaffolds for regeneration of cartilage and subchondral bone interface
Theranostics, 2018Co-Authors: Cuijun Deng, Jiayi Li, Chun Feng, Liming Wang, Jiang Chang, Chengtie WuAbstract:: The cartilage lesion resulting from osteoarthritis (OA) always extends into subchondral bone. It is of great importance for simultaneous regeneration of two tissues of cartilage and subchondral bone. 3D-printed Sr5(PO4)2SiO4 (SPS) bioactive ceramic scaffolds may achieve the aim of regenerating both of cartilage and subchondral bone. We hypothesized that strontium (Sr) and silicon (Si) ions released from SPS scaffolds play a crucial role in Osteochondral Defect reconstruction. Methods: SPS bioactive ceramic scaffolds were fabricated by a 3D-printing method. The SEM and ICPAES were used to investigate the physicochemical properties of SPS scaffolds. The proliferation and maturation of rabbit chondrocytes stimulated by SPS bioactive ceramics were measured in vitro. The stimulatory effect of SPS scaffolds for cartilage and subchondral bone regeneration was investigated in vivo. Results: SPS scaffolds significantly stimulated chondrocyte proliferation, and SPS extracts distinctly enhanced the maturation of chondrocytes and preserved chondrocytes from OA. SPS scaffolds markedly promoted the regeneration of Osteochondral Defects. The complex interface microstructure between cartilage and subchondral bone was obviously reconstructed. The underlying mechanism may be related to Sr and Si ions stimulating cartilage regeneration by activating HIF pathway and promoting subchondral bone reconstruction through activating Wnt pathway, as well as preserving chondrocytes from OA via inducing autophagy and inhibiting hedgehog pathway. Conclusion: Our findings suggest that SPS scaffolds can help Osteochondral Defect reconstruction and well reconstruct the complex interface between cartilage and subchondral bone, which represents a promising strategy for Osteochondral Defect regeneration.
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the maturity of tissue engineered cartilage in vitro affects the repairability for Osteochondral Defect
Tissue Engineering Part A, 2011Co-Authors: Cheng Zhe Jin, Liming Wang, Jae Ho Cho, Byung Hyune Choi, Moon Suk Kim, So Ra Park, Jeong Ho Yoon, Byounghyun MinAbstract:Cartilage tissue engineering using cells and biocompatible scaffolds has emerged as a promising approach to repair of cartilage damage. To date, however, no engineered cartilage has proven to be equivalent to native cartilage in terms of biochemical and compression properties, as well as histological features. An alternative strategy for cartilage engineering is to focus on the in vivo regeneration potential of immature engineered cartilage. Here, we used a rabbit model to evaluate the extent to which the maturity of engineered cartilage influenced the remodeling and integration of implanted extracellular matrix scaffolds containing allogenous chondrocytes. Full-thickness Osteochondral Defects were created in the trochlear groove of New Zealand white rabbits. Left knee Defects were left untreated as a control (group 1), and right knee Defects were implanted with tissue-engineered cartilage cultured in vitro for 2 days (group 2), 2 weeks (group 3), or 4 weeks (group 4). Histological, chemical, and compression assays of engineered cartilage in vitro showed that biochemical composition became more cartilagenous, and biomechanical property for compression gradually increased with culture time. In an in vivo study, gross imaging and histological observation at 1 and 3 months after implanting in vitro-cultured engineered cartilage showed that Defects in groups 3 and 4 were repaired with hyaline cartilage-like tissue, whereas Defects were only partially filled with fibrocartilage after 1 month in groups 1 and 2. At 3 months, group 4 showed striking features of hyaline cartilage tissue, with a mature matrix and a columnar arrangement of chondrocytes. Zonal distribution of type II collagen was most prominent, and the International Cartilage Repair Society score was also highest at this time. In addition, the subchondral bone was well ossified. In conclusion, in vivo engineered cartilage was remodeled when implanted; however, its extent to maturity varied with cultivation period. Our results showed that the more matured the engineered cartilage was, the better repaired the Osteochondral Defect was, highlighting the importance of the in vitro cultivation period.
Carmen Evora - One of the best experts on this subject based on the ideXlab platform.
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comparative Osteochondral Defect repair stem cells versus chondrocytes versus bone morphogenetic protein 2 solely or in combination
European Cells & Materials, 2013Co-Authors: R Reyes, Martina K Pec, E Sanchez, C Del Rosario, Araceli Delgado, Carmen EvoraAbstract:Full-thickness articular cartilage damage does not resolve spontaneously. Studies with growth factors, implantation of autologous chondrocytes and mesenchymal stem cells have led to variable, to some extent inconsistent, results. This work compares Osteochondral knee-Defect repair in rabbits upon implantation of a previously described alginate/(poly(lactic-co-glycolic) acid (PLGA) Osteochondral scaffold in distinct conditions. Systems were either in vitro pre-cultured with a small number of allogeneic chondrocytes under fibroblast growth factor (FGF)-2 stimulation or the same amount of allogeneic, marrow derived, mesenchymal stem cells (without any pre-differentiation), or loaded with microsphere-encapsulated bone morphogenetic protein (BMP)-2 within the alginate layer, or holding combinations of one or the other cell type with BMP-2. The experimental limit was 12 weeks, because a foregoing study with this release system had shown a maintained tissue response for at least 24 weeks post-operation. After only 6 weeks, histological analyses revealed newly formed cartilage-like tissue, which resembled the adjacent, normal cartilage in cell as well as BMP-2 treated Defects, but cell therapy gave higher histological scores. This advantage evened out until 12 weeks. Combinations of cells and BMP-2 did not result in any additive or synergistic effect. Equally efficient Osteochondral Defect repair was achieved with chondrocyte, stem cell, and BMP-2 treatment. Expression of collagen X and collagen I, signs of ongoing ossification, were histologically undetectable, and the presence of aggrecan protein indicated cartilage-like tissue. In conclusion, further work should demonstrate whether spatiotemporally controlled, on-site BMP-2 release alone could become a feasible therapeutic approach to repair large Osteochondral Defects.
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repair of an Osteochondral Defect by sustained delivery of bmp 2 or tgfβ1 from a bilayered alginate plga scaffold
Journal of Tissue Engineering and Regenerative Medicine, 2012Co-Authors: R Reyes, E Sanchez, Araceli Delgado, A Fernandez, Antonio Hernandez, Carmen EvoraAbstract:Regeneration of cartilage Defects can be accelerated by localized delivery of appropriate growth factors (GFs) from scaffolds. In the present study we analysed the in vitro and in vivo release rates and delivery efficacies of transforming growth factor-β1 (TGFβ1) and bone morphogenetic protein-2 (BMP-2) from a bilayered system, applied for Osteochondral Defect repair in a rabbit model. A bone-orientated, porous PLGA cylinder was overlaid with GF containing PLGA microspheres, dispersed in an alginate matrix. Four microsphere formulations were incorporated: (a) blank ones; (b) microspheres containing 50 ng TGFβ1; (c) microspheres containing 2.5 µg BMP-2; and (d) microspheres containing 5 µg BMP-2. Release kinetics and tissue distributions were determined using iodinated (125I) GFs. Bioactivity of in vitro released BMP-2 and TGFβ1 was confirmed in cell-based assays. In vivo release profiles indicated good GF release control. 20% of BMP-2 and 15% of TGFβ1 were released during the first day. Virtually the total dose was delivered at the end of week 6. Significant histological differences were observed between untreated and GF-treated specimens, there being especially relevant short-term outcomes with 50 ng TGFβ1 and 5 µg BMP-2. Although the evaluation scores for the newly formed cartilage did not differ significantly, 5 µg BMP-2 gave rise to higher quality cartilage with improved surface regularity, tissue integration and increased collagen-type II and aggrecan immunoreactivity 2 weeks post-implantation. Hence, the bilayered system controlled GF release rates and led to preserved cartilage integrity from 12 weeks up to at least 24 weeks. Copyright © 2012 John Wiley & Sons, Ltd.
Nobuto Kitamura - One of the best experts on this subject based on the ideXlab platform.
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effects of Osteochondral Defect size on cartilage regeneration using a double network hydrogel
BMC Musculoskeletal Disorders, 2017Co-Authors: Nobuto Kitamura, Fuminori Kanaya, Takayuki Kurokawa, Jian Ping Gong, Kotaro Higa, Keiko Goto, Kazunori YasudaAbstract:There has been increased interest in one-step cell-free procedures to avoid the problems related to cell manipulation and its inherent disadvantages. We have studied the chondrogenic induction ability of a PAMPS/PDMAAm double-network (DN) gel and found it to induce chondrogenesis in animal Osteochondral Defect models. The purpose of this study was to investigate whether the healing process and the degree of cartilage regeneration induced by the cell-free method using DN gel are influenced by the size of Osteochondral Defects. A total of 63 mature female Japanese white rabbits were used in this study, randomly divided into 3 groups of 21 rabbits each. A 2.5-mm diameter Osteochondral Defect was created in the femoral trochlea of the patellofemoral joint of bilateral knees in Group I, a 4.3-mm Osteochondral Defect in Group II, and a 5.8-mm Osteochondral Defect in Group III. In the right knee of each animal, a DN gel plug was implanted so that a vacant space of 2-mm depth was left above the plug. In the left knee, we did not conduct any treatment to obtain control data. Animals were sacrificed at 2, 4, and 12 weeks after surgery, and gross and histological evaluations were made. The present study demonstrated that all sizes of the DN gel implanted Defects as well as the 2.5mm untreated Defects showed cartilage regeneration at 4 and 12 weeks. The 4.3-mm and 5.8-mm untreated Defects did not show cartilage regeneration during the 12-week period. The quantitative score reported by O’Driscoll et al. was significantly higher in the 4.3-mm and 5.8-mm DN gel-implanted Defects than the untreated Defects at 4 and 12 weeks (p < 0.05). The 2.5-mm and 4.3-mm DN gel implanted Defects maintained relatively high macroscopic and histological scores for the 12-week implantation period, while the histological score of the 5.8-mm DN gel implanted Defect had decreased somewhat but statistically significantly at 12 weeks (p = 0.0057). The DN gel induced cartilage regeneration in Defects between 2.5 and 5.8 mm, offering a promising device to establish a cell-free cartilage regeneration therapy and applicable to various sizes of Osteochondral Defects.
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hydroxyapatite coated double network hydrogel directly bondable to the bone biological and biomechanical evaluations of the bonding property in an Osteochondral Defect
Acta Biomaterialia, 2016Co-Authors: Susumu Wada, Nobuto Kitamura, Takayuki Kurokawa, Jian Ping Gong, Takayuki Nonoyama, Ryuji Kiyama, Kazunori YasudaAbstract:Abstract We have developed a novel hydroxyapatite (HAp)-coated double-network (DN) hydrogel (HAp/DN gel). The purpose of this study was to determine details of the cell and tissue responses around the implanted HAp/DN gel and to determine how quickly and strongly the HAp/DN gel bonds to the bone in a rabbit Osteochondral Defect model. Immature osteoid tissue was formed in the space between the HAp/DN gel and the bone at 2 weeks, and the osteoid tissue was mineralized at 4 weeks. The push-out load of the HAp/DN gel averaged 37.54 N and 42.15 N at 4 and 12 weeks, respectively, while the push-out load of the DN gel averaged less than 5 N. The bonding area of the HAp/DN gel to the bone was above 80% by 4 weeks, and above 90% at 12 weeks. This study demonstrated that the HAp/DN gel enhanced osseointegration at an early stage after implantation. The presence of nanoscale structures in addition to osseointegration of HAp promoted osteoblast adhesion onto the surface of the HAp/DN gel. The HAp/DN gel has the potential to improve the implant-tissue interface in next-generation orthopaedic implants such as artificial cartilage. Statement of Significance Recent studies have reported the development of various hydrogels that are sufficiently tough for application as soft supporting tissues. However, fixation of hydrogels on bone surfaces with appropriate strength is a great challenge. We have developed a novel, tough hydrogel hybridizing hydroxyapatite (HAp/DN gel), which is directly bondable to the bone. The present study demonstrated that the HAp/DN gel enhanced osseointegration in the early stage after implantation. The presence of nanoscale structures in addition to the osseointegration ability of hydroxyapatite promoted osteoblast adhesion onto the surface of the HAp/DN gel. The HAp/DN gel has the potential to improve the implant-tissue interface in next-generation orthopaedic implants such as artificial cartilage.
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intra articular administration of hyaluronic acid increases the volume of the hyaline cartilage regenerated in a large Osteochondral Defect by implantation of a double network gel
Journal of Materials Science: Materials in Medicine, 2014Co-Authors: Takaaki Fukui, Nobuto Kitamura, Takayuki Kurokawa, Jian Ping Gong, Masashi Yokota, Eiji Kondo, Kazunori YasudaAbstract:Implantation of PAMPS/PDMAAm double-network (DN) gel can induce hyaline cartilage regeneration in the Osteochondral Defect. However, it is a problem that the volume of the regenerated cartilage tissue is gradually reduced at 12 weeks. This study investigated whether intra-articular administration of hyaluronic acid (HA) increases the volume of the cartilage regenerated with the DN gel at 12 weeks. A total of 48 rabbits were used in this study. A cylindrical Osteochondral Defect created in the bilateral femoral trochlea was treated with DN gel (Group DN) or left without any implantation (Group C). In both Groups, we injected 1.0 mL of HA in the left knee, and 1.0 mL of saline solution in the right knee. Quantitative histological evaluations were performed at 2, 4, and 12 weeks, and PCR analysis was performed at 2 and 4 weeks after surgery. In Group DN, the proteoglycan-rich area was significantly greater in the HA-injected knees than in the saline-injected knees at 12 weeks (P = 0.0247), and expression of type 2 collagen, aggrecan, and Sox9 mRNAs was significantly greater in the HA-injected knees than in the saline-injected knees at 2 weeks (P = 0.0475, P = 0.0257, P = 0.0222, respectively). The intra-articular administration of HA significantly enhanced these gene expression at 2 weeks and significantly increased the volume of the hyaline cartilage regenerated by implantation of a DN gel at 12 weeks. This information is important to develop an additional method to increase the volume of the hyaline cartilage tissue in a potential cartilage regeneration strategy using the DN gel.
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influence of the gel thickness on in vivo hyaline cartilage regeneration induced by double network gel implanted at the bottom of a large Osteochondral Defect short term results
BMC Musculoskeletal Disorders, 2013Co-Authors: Kazunobu Arakaki, Nobuto Kitamura, Hidetoshi Matsuda, Fuminori Kanaya, Takayuki Kurokawa, Jian Ping Gong, Kazunori YasudaAbstract:Background A double-network (DN) gel, which is composed of poly(2-acrylamido-2-methylpropanesulfonic acid) and poly(N,N’-dimethyl acrylamide), can induce hyaline cartilage regeneration in vivo in a large Osteochondral Defect. The purpose of this study was to clarify the influence of the thickness of the implanted DN gel on the induction ability of hyaline cartilage regeneration.
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influence of the gel thickness on in vivo hyaline cartilage regeneration induced by double network gel implanted at the bottom of a large Osteochondral Defect short term results
BMC Musculoskeletal Disorders, 2013Co-Authors: Kazunobu Arakaki, Nobuto Kitamura, Hidetoshi Matsuda, Fuminori Kanaya, Takayuki Kurokawa, Jian Ping Gong, Kazunori YasudaAbstract:A double-network (DN) gel, which is composed of poly(2-acrylamido-2-methylpropanesulfonic acid) and poly(N,N’-dimethyl acrylamide), can induce hyaline cartilage regeneration in vivo in a large Osteochondral Defect. The purpose of this study was to clarify the influence of the thickness of the implanted DN gel on the induction ability of hyaline cartilage regeneration. Thirty-eight mature rabbits were used in this study. We created an Osteochondral Defect having a diameter of 4.3-mm in the patellofemoral joint. The knees were randomly divided into 4 groups (Group I: 0.5-mm thick gel, Group II: 1.0-mm thick gel, Group III: 5.0-mm thick gel, and Group IV: untreated control). Animals in each group were further divided into 3 sub-groups depending on the gel implant position (2.0-, 3.0-, or 4.0-mm depth from the articular surface) in the Defect. The regenerated tissues were evaluated with the Wayne’s gross and histological grading scales and real time PCR analysis of the cartilage marker genes at 4 weeks. According to the total Wayne’s score, when the depth of the final vacant space was set at 2.0 mm, the scores in Groups I, II, and III were significantly greater than that Group IV (p < 0.05), although there were no significant differences between Groups I and IV at a 3.0-mm deep vacant space. The expression levels of type-2 collagen in Groups II and III were significantly higher (p < 0.05) than that in Group IV. The 1.0-mm thick DN gel sheet had the same ability to induce hyaline cartilage regeneration as the 5.0-mm thick DN gel plug. However, the induction ability of the 0.5-mm thick sheet was significantly lower when compared with the 1.0-mm thick gel sheet. The 1.0-mm DN gel sheet is a promising device to establish a cell-free cartilage regeneration strategy that minimizes bone loss from the gel implantation.
