Pub Date : 2024-04-27eCollection Date: 2024-01-01DOI: 10.1093/rb/rbae044
Yuntao Di, Lu Wang, Wei He, Shuyan Liu, Yuqi He, Jie Liao, Ruihong Zhang, Lan Yin, Zhiwei Xu, Xiaoming Li
Polypropylene (PP) mesh is commonly used in abdominal wall repair due to its ability to reduce the risk of organ damage, infections and other complications. However, the PP mesh often leads to adhesion formation and does not promote functional tissue repair. In this study, we synthesized one kind of aldehyde Bletilla striata polysaccharide (BSPA) modified chitosan (CS) hydrogel based on Schiff base reaction. The hydrogel exhibited a porous network structure, a highly hydrophilic surface and good biocompatibility. We wrapped the PP mesh inside the hydrogel and evaluated the performance of the resulting composites in a bilateral 1 × 1.5 cm abdominal wall defect model in rats. The results of gross observation, histological staining and immunohistochemical staining demonstrated the positive impact of the CS hydrogel on anti-adhesion and wound healing effects. Notably, the addition of BSPA to the CS hydrogel further improved the performance of the composites in vivo, promoting wound healing by enhancing collagen deposition and capillary rearrangement. This study suggested that the BSPA-modified CS hydrogel significantly promoted the anti-adhesion, anti-inflammatory and pro-angiogenesis properties of PP meshes during the healing process. Overall, this work offers a novel approach to the design of abdominal wall repair patches.
{"title":"The utilization of chitosan/<i>Bletilla striata</i> hydrogels to elevate anti-adhesion, anti-inflammatory and pro-angiogenesis properties of polypropylene mesh in abdominal wall repair.","authors":"Yuntao Di, Lu Wang, Wei He, Shuyan Liu, Yuqi He, Jie Liao, Ruihong Zhang, Lan Yin, Zhiwei Xu, Xiaoming Li","doi":"10.1093/rb/rbae044","DOIUrl":"10.1093/rb/rbae044","url":null,"abstract":"<p><p>Polypropylene (PP) mesh is commonly used in abdominal wall repair due to its ability to reduce the risk of organ damage, infections and other complications. However, the PP mesh often leads to adhesion formation and does not promote functional tissue repair. In this study, we synthesized one kind of aldehyde <i>Bletilla striata</i> polysaccharide (BSPA) modified chitosan (CS) hydrogel based on Schiff base reaction. The hydrogel exhibited a porous network structure, a highly hydrophilic surface and good biocompatibility. We wrapped the PP mesh inside the hydrogel and evaluated the performance of the resulting composites in a bilateral 1 × 1.5 cm abdominal wall defect model in rats. The results of gross observation, histological staining and immunohistochemical staining demonstrated the positive impact of the CS hydrogel on anti-adhesion and wound healing effects. Notably, the addition of BSPA to the CS hydrogel further improved the performance of the composites <i>in vivo</i>, promoting wound healing by enhancing collagen deposition and capillary rearrangement. This study suggested that the BSPA-modified CS hydrogel significantly promoted the anti-adhesion, anti-inflammatory and pro-angiogenesis properties of PP meshes during the healing process. Overall, this work offers a novel approach to the design of abdominal wall repair patches.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"11 ","pages":"rbae044"},"PeriodicalIF":5.6,"publicationDate":"2024-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11220408/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141498801","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-04-24eCollection Date: 2024-01-01DOI: 10.1093/rb/rbae041
Jonas Wüster, Norbert Neckel, Florian Sterzik, Li Xiang-Tischhauser, Dirk Barnewitz, Antje Genzel, Steffen Koerdt, Carsten Rendenbach, Christian Müller-Mai, Max Heiland, Susanne Nahles, Christine Knabe
Lately, the potential risk of disease transmission due to the use of bovine-derived bone substitutes has become obvious, demonstrating the urgent need for a synthetic grafting material with comparable bioactive behaviour and properties. Therefore, the effect of a synthetic hydroxyapatite (HA) (Osbone®) bone grafting material on bone regeneration was evaluated 2 weeks, 1 month, and 3, 6, 12 and 18 months after implantation in critical-size bone defects in the ovine scapula and compared to that of a bovine-derived HA (Bio-Oss®) and β-tricalcium phosphate (TCP) (Cerasorb® M). New bone formation and the biodegradability of the bone substitutes were assessed histomorphometrically. Hard tissue histology and immunohistochemical analysis were employed to characterize collagen type I, alkaline phosphatase, osteocalcin, as well as bone sialoprotein expression in the various cell and matrix components of the bone tissue to evaluate the bioactive properties of the bone grafting materials. No inflammatory tissue response was detected with any of the bone substitute materials studied. After 3 and 6 months, β-TCP (Cerasorb® M) showed superior bone formation when compared to both HA-based materials (3 months: β-TCP 55.65 ± 2.03% vs. SHA 49.05 ± 3.84% and BHA 47.59 ± 1.97%; p ≤0.03; 6 months: β-TCP 62.03 ± 1.58%; SHA: 55.83 ± 2.59%; BHA: 53.44 ± 0.78%; p ≤0.04). Further, after 12 and 18 months, a similar degree of bone formation and bone-particle contact was noted for all three bone substitute materials without any significant differences. The synthetic HA supported new bone formation, osteogenic marker expression, matrix mineralization and good bone-bonding behaviour to an equal and even slightly superior degree compared to the bovine-derived HA. As a result, synthetic HA can be regarded as a valuable alternative to the bovine-derived HA without the potential risk of disease transmission.
近来,使用牛源性骨替代物所带来的潜在疾病传播风险已变得十分明显,这表明迫切需要一种具有可比生物活性行为和特性的合成植骨材料。因此,我们评估了合成羟基磷灰石 (HA) (Osbone®) 骨移植材料在雌性肩胛骨临界大小骨缺损中植入 2 周、1 个月、3、6、12 和 18 个月后对骨再生的影响,并与牛源性 HA (Bio-Oss®) 和 β-磷酸三钙 (TCP) (Cerasorb® M) 进行了比较。新骨形成和骨替代物的生物降解性通过组织形态计量学进行评估。采用硬组织组织学和免疫组化分析来确定骨组织各种细胞和基质成分中 I 型胶原蛋白、碱性磷酸酶、骨钙素以及骨硅蛋白的表达,以评估骨移植材料的生物活性特性。所研究的骨替代材料均未发现炎症组织反应。3 个月和 6 个月后,β-TCP(Cerasorb® M)的骨形成优于两种基于 HA 的材料(3 个月:β-TCP 55.65 ± 2.03% vs. SHA 49.05 ± 3.84% 和 BHA 47.59 ± 1.97%;p ≤ 0.03;6 个月:β-TCP 62.03 ± 1.58%;SHA:55.83 ± 2.59%;BHA:53.44 ± 0.78%;p ≤ 0.04)。此外,12 个月和 18 个月后,三种骨替代材料的骨形成和骨颗粒接触程度相似,没有明显差异。与牛源性 HA 相比,合成 HA 对新骨形成、成骨标志物表达、基质矿化和良好的骨结合性能的支持程度相当,甚至略胜一筹。因此,合成 HA 可被视为牛源性 HA 的一种有价值的替代品,而且没有潜在的疾病传播风险。
{"title":"Effect of a synthetic hydroxyapatite-based bone grafting material compared to established bone substitute materials on regeneration of critical-size bone defects in the ovine scapula.","authors":"Jonas Wüster, Norbert Neckel, Florian Sterzik, Li Xiang-Tischhauser, Dirk Barnewitz, Antje Genzel, Steffen Koerdt, Carsten Rendenbach, Christian Müller-Mai, Max Heiland, Susanne Nahles, Christine Knabe","doi":"10.1093/rb/rbae041","DOIUrl":"10.1093/rb/rbae041","url":null,"abstract":"<p><p>Lately, the potential risk of disease transmission due to the use of bovine-derived bone substitutes has become obvious, demonstrating the urgent need for a synthetic grafting material with comparable bioactive behaviour and properties. Therefore, the effect of a synthetic hydroxyapatite (HA) (Osbone<sup>®</sup>) bone grafting material on bone regeneration was evaluated 2 weeks, 1 month, and 3, 6, 12 and 18 months after implantation in critical-size bone defects in the ovine scapula and compared to that of a bovine-derived HA (Bio-Oss<sup>®</sup>) and β-tricalcium phosphate (TCP) (Cerasorb<sup>®</sup> M). New bone formation and the biodegradability of the bone substitutes were assessed histomorphometrically. Hard tissue histology and immunohistochemical analysis were employed to characterize collagen type I, alkaline phosphatase, osteocalcin, as well as bone sialoprotein expression in the various cell and matrix components of the bone tissue to evaluate the bioactive properties of the bone grafting materials. No inflammatory tissue response was detected with any of the bone substitute materials studied. After 3 and 6 months, β-TCP (Cerasorb<sup>®</sup> M) showed superior bone formation when compared to both HA-based materials (3 months: β-TCP 55.65 ± 2.03% vs. SHA 49.05 ± 3.84% and BHA 47.59 ± 1.97%; <i>p </i>≤<i> </i>0.03; 6 months: β-TCP 62.03 ± 1.58%; SHA: 55.83 ± 2.59%; BHA: 53.44 ± 0.78%; <i>p </i>≤<i> </i>0.04). Further, after 12 and 18 months, a similar degree of bone formation and bone-particle contact was noted for all three bone substitute materials without any significant differences. The synthetic HA supported new bone formation, osteogenic marker expression, matrix mineralization and good bone-bonding behaviour to an equal and even slightly superior degree compared to the bovine-derived HA. As a result, synthetic HA can be regarded as a valuable alternative to the bovine-derived HA without the potential risk of disease transmission.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"11 ","pages":"rbae041"},"PeriodicalIF":5.6,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11187503/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141432593","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Despite a growing body of studies demonstrating the specific antitumor effect of nano-hydroxyapatite (n-HA), the underlying mechanism remained unclear. Endoplasmic reticulum (ER) and mitochondria are two key players in intracellular Ca2+ homeostasis and both require Ca2+ to participate. Moreover, the ER-mitochondria interplay coordinates the maintenance of cellular calcium homeostasis to prevent any negative consequences from excess of Ca2+, hence there needs in-depth study of n-HA effect on them. In this study, we fabricated needle-like n-HA to investigate the antitumor effectiveness as well as the underlying mechanisms from cellular and molecular perspectives. Data from in vitro experiments indicated that the growth and invasion of glioma cells were obviously reduced with the aid of n-HA. It's interesting to note that the expression of ER stress biomarkers (GRP78, p-IRE1, p-PERK, PERK, and ATF6) were all up-regulated after n-HA treatment, along with the activation of the pro-apoptotic transcription factor CHOP, showing that ER stress produced by n-HA triggered cell apoptosis. Moreover, the increased expression level of intracellular reactive oxygen species (ROS) and the mitochondrial membrane depolarization, as well as the downstream cell apoptotic signaling activation, further demonstrated the pro-apoptotic roles of n-HA induced Ca2+ overload through inducing mitochondria damage. The in vivo data provided additional evidence that n-HA caused ER stress and mitochondria damage in cells and effectively restrain the growth of glioma tumors. Collectively, the work showed that n-HA co-activated intracellular ER stress and mitochondria damage are critical triggers for cancer cells apoptosis, offering fresh perspectives on ER-mitochondria targeted anti-tumor therapy.
{"title":"Nano-hydroxyapatite promotes cell apoptosis by co-activating endoplasmic reticulum stress and mitochondria damage to inhibit glioma growth","authors":"Yifu Wang, Hongfeng Wu, Zhu Chen, Jun Cao, Xiangdong Zhu, Xingdong Zhang","doi":"10.1093/rb/rbae038","DOIUrl":"https://doi.org/10.1093/rb/rbae038","url":null,"abstract":"Despite a growing body of studies demonstrating the specific antitumor effect of nano-hydroxyapatite (n-HA), the underlying mechanism remained unclear. Endoplasmic reticulum (ER) and mitochondria are two key players in intracellular Ca2+ homeostasis and both require Ca2+ to participate. Moreover, the ER-mitochondria interplay coordinates the maintenance of cellular calcium homeostasis to prevent any negative consequences from excess of Ca2+, hence there needs in-depth study of n-HA effect on them. In this study, we fabricated needle-like n-HA to investigate the antitumor effectiveness as well as the underlying mechanisms from cellular and molecular perspectives. Data from in vitro experiments indicated that the growth and invasion of glioma cells were obviously reduced with the aid of n-HA. It's interesting to note that the expression of ER stress biomarkers (GRP78, p-IRE1, p-PERK, PERK, and ATF6) were all up-regulated after n-HA treatment, along with the activation of the pro-apoptotic transcription factor CHOP, showing that ER stress produced by n-HA triggered cell apoptosis. Moreover, the increased expression level of intracellular reactive oxygen species (ROS) and the mitochondrial membrane depolarization, as well as the downstream cell apoptotic signaling activation, further demonstrated the pro-apoptotic roles of n-HA induced Ca2+ overload through inducing mitochondria damage. The in vivo data provided additional evidence that n-HA caused ER stress and mitochondria damage in cells and effectively restrain the growth of glioma tumors. Collectively, the work showed that n-HA co-activated intracellular ER stress and mitochondria damage are critical triggers for cancer cells apoptosis, offering fresh perspectives on ER-mitochondria targeted anti-tumor therapy.","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"199 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140625422","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-26eCollection Date: 2024-01-01DOI: 10.1093/rb/rbae035
Delong Zhu, Ying Hu, Xiangkai Kong, Yuansen Luo, Yi Zhang, Yu Wu, Jiameng Tan, Jianwei Chen, Tao Xu, Lei Zhu
Adipose mesenchymal stem cell (ADMSC)-derived exosomes (ADMSC-Exos) have shown great potential in regenerative medicine and been evidenced benefiting wound repair such as burns. However, the low yield, easy loss after direct coating, and no suitable loading system to improve their availability and efficacy hinder their clinical application for wound healing. And few studies focused on the comparison of biological functions between exosomes derived from different culture techniques, especially in exosome-releasing hydrogel system. Therefore, we designed a high-performance exosome controllable releasing hydrogel system for burn wound healing, namely loading 3D-printed microfiber culture-derived exosomes in a highly biocompatible hyaluronic acid (HA). In this project, we compared the biological functions in vitro and in a burn model among exosomes derived from the conventional two-dimensional (2D) plate culture (2D-Exos), microcarrier culture (2.5D-Exos), and 3D-printed microfiber culture (3D-Exos). Results showed that compared with 2D-Exos and 2.5D-Exos, 3D-Exos promoted HACATs and HUVECs cell proliferation and migration more significantly. Additionally, 3D-Exos had stronger angiogenesis-promoting effects in tube formation of (HUVECs) cells. Moreover, we found HA-loaded 3D-Exos showed better burn wound healing promotion compared to 2D-Exos and 2.5D-Exos, including accelerated burn wound healing rate and better collagen remodeling. The study findings reveal that the HA-loaded, controllable-release 3D-Exos repair system distinctly augments therapeutic efficacy in terms of wound healing, while concurrently introducing a facile application approach. This system markedly bolsters the exosomal loading efficiency, provides a robust protective milieu, and potentiates the inherent biological functionalities of the exosomes. Our findings provide a rationale for more efficient utilization of high-quality and high-yield 3D exosomes in the future, and a novel strategy for healing severe burns.
{"title":"Enhanced burn wound healing by controlled-release 3D ADMSC-derived exosome-loaded hyaluronan hydrogel.","authors":"Delong Zhu, Ying Hu, Xiangkai Kong, Yuansen Luo, Yi Zhang, Yu Wu, Jiameng Tan, Jianwei Chen, Tao Xu, Lei Zhu","doi":"10.1093/rb/rbae035","DOIUrl":"https://doi.org/10.1093/rb/rbae035","url":null,"abstract":"<p><p>Adipose mesenchymal stem cell (ADMSC)-derived exosomes (ADMSC-Exos) have shown great potential in regenerative medicine and been evidenced benefiting wound repair such as burns. However, the low yield, easy loss after direct coating, and no suitable loading system to improve their availability and efficacy hinder their clinical application for wound healing. And few studies focused on the comparison of biological functions between exosomes derived from different culture techniques, especially in exosome-releasing hydrogel system. Therefore, we designed a high-performance exosome controllable releasing hydrogel system for burn wound healing, namely loading 3D-printed microfiber culture-derived exosomes in a highly biocompatible hyaluronic acid (HA). In this project, we compared the biological functions <i>in vitro</i> and in a burn model among exosomes derived from the conventional two-dimensional (2D) plate culture (2D-Exos), microcarrier culture (2.5D-Exos), and 3D-printed microfiber culture (3D-Exos). Results showed that compared with 2D-Exos and 2.5D-Exos, 3D-Exos promoted HACATs and HUVECs cell proliferation and migration more significantly. Additionally, 3D-Exos had stronger angiogenesis-promoting effects in tube formation of (HUVECs) cells. Moreover, we found HA-loaded 3D-Exos showed better burn wound healing promotion compared to 2D-Exos and 2.5D-Exos, including accelerated burn wound healing rate and better collagen remodeling. The study findings reveal that the HA-loaded, controllable-release 3D-Exos repair system distinctly augments therapeutic efficacy in terms of wound healing, while concurrently introducing a facile application approach. This system markedly bolsters the exosomal loading efficiency, provides a robust protective milieu, and potentiates the inherent biological functionalities of the exosomes. Our findings provide a rationale for more efficient utilization of high-quality and high-yield 3D exosomes in the future, and a novel strategy for healing severe burns.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"11 ","pages":"rbae035"},"PeriodicalIF":6.7,"publicationDate":"2024-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11018541/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870144","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Platelet-rich plasma (PRP) is one of the most popular biomaterials in regenerative medicine. However, the difficulties encountered in its preservation, and the requirement for on-demand preparation severely limit its application. In addition, its rapid degradation in the wound microenvironment makes the sustained release of growth factors impossible and finally reduces the therapeutic effect on chronic wounds. Here, a multifunctional dressing based on triple-layered core-shell fibers for loading and enduring preservation of PRP was developed using a one-step coaxial bioprinting technique combined with freeze-drying. The platelets were effectively dispersed and immobilized in the core layer of the fiber, leading to a sustained release of growth factors from the PRP. The rate of release can be controlled by adjusting the triple-layered core-shell structure. Simultaneously, the triple-layered core-shell structure can reduce the deactivation of PRP during freezing and storage. The experimental findings suggest that PRP exhibits sustained activity, facilitating the process of wound healing even after a storage period of 180 days. Furthermore, the protective mechanism of PRP by the triple-layered core-shell fiber was investigated, and the conditions for freeze-drying and storage were optimized, further enhancing the long-term storability of PRP. As a result, the multifunctional core-shell fiber dressings developed in this study offer a novel approach for sustained growth factor release and the enduring preservation of active PRP.
{"title":"Triple-layered core-shell fiber dressings with enduring platelet conservation and sustained growth factor release abilities for chronic wound healing.","authors":"Simin Lai, Tingbin Wu, Chenxi Shi, Xiaojing Wang, Pengbi Liu, Lihuan Wang, Hui Yu","doi":"10.1093/rb/rbae034","DOIUrl":"https://doi.org/10.1093/rb/rbae034","url":null,"abstract":"<p><p>Platelet-rich plasma (PRP) is one of the most popular biomaterials in regenerative medicine. However, the difficulties encountered in its preservation, and the requirement for on-demand preparation severely limit its application. In addition, its rapid degradation in the wound microenvironment makes the sustained release of growth factors impossible and finally reduces the therapeutic effect on chronic wounds. Here, a multifunctional dressing based on triple-layered core-shell fibers for loading and enduring preservation of PRP was developed using a one-step coaxial bioprinting technique combined with freeze-drying. The platelets were effectively dispersed and immobilized in the core layer of the fiber, leading to a sustained release of growth factors from the PRP. The rate of release can be controlled by adjusting the triple-layered core-shell structure. Simultaneously, the triple-layered core-shell structure can reduce the deactivation of PRP during freezing and storage. The experimental findings suggest that PRP exhibits sustained activity, facilitating the process of wound healing even after a storage period of 180 days. Furthermore, the protective mechanism of PRP by the triple-layered core-shell fiber was investigated, and the conditions for freeze-drying and storage were optimized, further enhancing the long-term storability of PRP. As a result, the multifunctional core-shell fiber dressings developed in this study offer a novel approach for sustained growth factor release and the enduring preservation of active PRP.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"11 ","pages":"rbae034"},"PeriodicalIF":6.7,"publicationDate":"2024-03-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11004556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140852599","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-03-21eCollection Date: 2024-01-01DOI: 10.1093/rb/rbae029
Tun Wang, Peng Lu, Zicheng Wan, Zhenyu He, Siyuan Cheng, Yang Zhou, Sheng Liao, Mo Wang, Tianjian Wang, Chang Shu
Arteriovenous grafts (AVGs) have emerged as the preferred option for constructing hemodialysis access in numerous patients. Clinical trials have demonstrated that decellularized vascular graft exhibits superior patency and excellent biocompatibility compared to polymer materials; however, it still faces challenges such as intimal hyperplasia and luminal dilation. The absence of suitable animal models hinders our ability to describe and explain the pathological phenomena above and in vivo adaptation process of decellularized vascular graft at the molecular level. In this study, we first collected clinical samples from patients who underwent the construction of dialysis access using allogeneic decellularized vascular graft, and evaluated their histological features and immune cell infiltration status 5 years post-transplantation. Prior to the surgery, we assessed the patency and intimal hyperplasia of the decellularized vascular graft using non-invasive ultrasound. Subsequently, in order to investigate the in vivo adaptation of decellularized vascular grafts in an animal model, we attempted to construct an AVG model using decellularized vascular grafts in a small animal model. We employed a physical-chemical-biological approach to decellularize the rat carotid artery, and histological evaluation demonstrated the successful removal of cellular and antigenic components while preserving extracellular matrix constituents such as elastic fibers and collagen fibers. Based on these results, we designed and constructed the first allogeneic decellularized rat carotid artery AVG model, which exhibited excellent patency and closely resembled clinical characteristics. Using this animal model, we provided a preliminary description of the histological features and partial immune cell infiltration in decellularized vascular grafts at various time points, including Day 7, Day 21, Day 42, and up to one-year post-implantation. These findings establish a foundation for further investigation into the in vivo adaptation process of decellularized vascular grafts in small animal model.
{"title":"Adaptation process of decellularized vascular grafts as hemodialysis access <i>in vivo</i>.","authors":"Tun Wang, Peng Lu, Zicheng Wan, Zhenyu He, Siyuan Cheng, Yang Zhou, Sheng Liao, Mo Wang, Tianjian Wang, Chang Shu","doi":"10.1093/rb/rbae029","DOIUrl":"https://doi.org/10.1093/rb/rbae029","url":null,"abstract":"<p><p>Arteriovenous grafts (AVGs) have emerged as the preferred option for constructing hemodialysis access in numerous patients. Clinical trials have demonstrated that decellularized vascular graft exhibits superior patency and excellent biocompatibility compared to polymer materials; however, it still faces challenges such as intimal hyperplasia and luminal dilation. The absence of suitable animal models hinders our ability to describe and explain the pathological phenomena above and <i>in vivo</i> adaptation process of decellularized vascular graft at the molecular level. In this study, we first collected clinical samples from patients who underwent the construction of dialysis access using allogeneic decellularized vascular graft, and evaluated their histological features and immune cell infiltration status 5 years post-transplantation. Prior to the surgery, we assessed the patency and intimal hyperplasia of the decellularized vascular graft using non-invasive ultrasound. Subsequently, in order to investigate the <i>in vivo</i> adaptation of decellularized vascular grafts in an animal model, we attempted to construct an AVG model using decellularized vascular grafts in a small animal model. We employed a physical-chemical-biological approach to decellularize the rat carotid artery, and histological evaluation demonstrated the successful removal of cellular and antigenic components while preserving extracellular matrix constituents such as elastic fibers and collagen fibers. Based on these results, we designed and constructed the first allogeneic decellularized rat carotid artery AVG model, which exhibited excellent patency and closely resembled clinical characteristics. Using this animal model, we provided a preliminary description of the histological features and partial immune cell infiltration in decellularized vascular grafts at various time points, including Day 7, Day 21, Day 42, and up to one-year post-implantation. These findings establish a foundation for further investigation into the <i>in vivo</i> adaptation process of decellularized vascular grafts in small animal model.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"11 ","pages":"rbae029"},"PeriodicalIF":6.7,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11026144/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140874792","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Peri-implant lesion is a grave condition afflicting numerous indi-viduals with dental implants. It results from persistent periodontal bacteria accumulation causing inflammation around the implant site, which can primarily lead to implant loosening and ultimately the implant loss. Early-stage peri-implant lesions exhibit symptoms akin to gum disease, including swelling, redness and bleeding of the gums surrounding the implant. These signs indicate infection and inflammation of the peri-implant tissues, which may result in bone loss and implant failure. To address this problem, a thermionic strategy was applied by designing a cuprorivaite-hardystonite bioceramic/alginate composite hydrogel with photothermal and Cu/Zn/Si multiple ions releasing property. This innovative approach creates a thermionic effect by the release of bioactive ions (Cu2+ and Zn2+ and ) from the composite hydrogel and the mild heat environment though the photothermal effect of the composite hydrogel induced by near-infrared light irradiation. The most distinctive advantage of this thermionic effect is to substantially eliminate periodontal pathogenic bacteria and inhibit inflammation, while simultaneously enhance peri-implant osseointegration. This unique attribute renders the use of this composite hydrogel highly effective in significantly improving the survival rate of implants after intervention in peri-implant lesions, which is a clinical challenge in periodontics. This study reveals application potential of a new biomaterial-based approach for peri-implant lesion, as it not only eliminates the infection and inflammation, but also enhances the osteointegration of the dental implant, which provides theoretical insights and practical guidance to prevent and manage early-stage peri-implant lesion using bioactive functional materials.
{"title":"Cuprorivaite/hardystonite/alginate composite hydrogel with thermionic effect for the treatment of peri-implant lesion.","authors":"Yiru Xia, Zhaowenbin Zhang, Kecong Zhou, Zhikai Lin, Rong Shu, Yuze Xu, Zhen Zeng, Jiang Chang, Yufeng Xie","doi":"10.1093/rb/rbae028","DOIUrl":"https://doi.org/10.1093/rb/rbae028","url":null,"abstract":"<p><p>Peri-implant lesion is a grave condition afflicting numerous indi-viduals with dental implants. It results from persistent periodontal bacteria accumulation causing inflammation around the implant site, which can primarily lead to implant loosening and ultimately the implant loss. Early-stage peri-implant lesions exhibit symptoms akin to gum disease, including swelling, redness and bleeding of the gums surrounding the implant. These signs indicate infection and inflammation of the peri-implant tissues, which may result in bone loss and implant failure. To address this problem, a thermionic strategy was applied by designing a cuprorivaite-hardystonite bioceramic/alginate composite hydrogel with photothermal and Cu/Zn/Si multiple ions releasing property. This innovative approach creates a thermionic effect by the release of bioactive ions (Cu<sup>2+</sup> and Zn<sup>2+</sup> and <math><mrow><msubsup><mrow><mtext>SiO</mtext></mrow><mrow><mn>3</mn></mrow><mrow><mn>2</mn><mo>-</mo></mrow></msubsup></mrow></math>) from the composite hydrogel and the mild heat environment though the photothermal effect of the composite hydrogel induced by near-infrared light irradiation. The most distinctive advantage of this thermionic effect is to substantially eliminate periodontal pathogenic bacteria and inhibit inflammation, while simultaneously enhance peri-implant osseointegration. This unique attribute renders the use of this composite hydrogel highly effective in significantly improving the survival rate of implants after intervention in peri-implant lesions, which is a clinical challenge in periodontics. This study reveals application potential of a new biomaterial-based approach for peri-implant lesion, as it not only eliminates the infection and inflammation, but also enhances the osteointegration of the dental implant, which provides theoretical insights and practical guidance to prevent and manage early-stage peri-implant lesion using bioactive functional materials.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"11 ","pages":"rbae028"},"PeriodicalIF":6.7,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11007117/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140870015","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Polyetherketoneketone (PEKK), a high-performance thermoplastic special engineering material, maintains bone-like mechanical properties and has received considerable attention in the biomedical field. The three-dimensional (3D) printing technique enables the production of porous scaffolds with a honeycomb structure featuring precisely controlled pore size, porosity, and interconnectivity, which holds significant potential for applications in tissue engineering. The ideal pore architecture of porous PEKK scaffolds has yet to be elucidated. Porous PEKK scaffolds with five pore sizes P200 (225 ± 9.8 μm), P400 (411 ± 22.1 μm), P600 (596 ± 23.4 μm), P800 (786 ± 24.2 μm), and P1000 (993 ± 26.0 μm) were produced by a 3D printer. Subsequently, the optimum pore size, the P600, for mechanical properties and osteogenesis was selected based on in vitro experiments. To improve the interfacial bioactivity of porous PEKK scaffolds, hydroxyapatite (HAp) crystals were generated via in situ biomimetic mineralization induced by the phase transited lysozyme (PTL) coating. Herein, a micro/nanostructured surface showing HAp crystals on PEKK scaffold was developed. In vitro and in vivo experiments confirmed that the porous PEKK-HAp scaffolds exhibited highly interconnected pores and functional surface structures that were favorable for biocompatibility and osteoinductivity, which boosted bone regeneration. Therefore, this work not only demonstrates that the pore structure of the P600 scaffold is suitable for PEKK orthopedic implants but also sheds light on a synergistic approach involving 3D printing and biomimetic mineralization, which has the potential to yield customized 3D PEKK-HAp scaffolds with enhanced osteoinductivity and osteogenesis, offering a promising strategy for bone tissue engineering.
{"title":"Bio-functional hydroxyapatite coated 3D porous polyetherketoneketone scaffold for enhanced osteogenesis and osteointegration in orthopedic applications","authors":"Huanhuan Liu, Taiqing Liu, Zhicheng Yin, Xiaoyin Liu, Ying Tan, Yuwei Zhao, Haiyang Yu","doi":"10.1093/rb/rbae023","DOIUrl":"https://doi.org/10.1093/rb/rbae023","url":null,"abstract":"Polyetherketoneketone (PEKK), a high-performance thermoplastic special engineering material, maintains bone-like mechanical properties and has received considerable attention in the biomedical field. The three-dimensional (3D) printing technique enables the production of porous scaffolds with a honeycomb structure featuring precisely controlled pore size, porosity, and interconnectivity, which holds significant potential for applications in tissue engineering. The ideal pore architecture of porous PEKK scaffolds has yet to be elucidated. Porous PEKK scaffolds with five pore sizes P200 (225 ± 9.8 μm), P400 (411 ± 22.1 μm), P600 (596 ± 23.4 μm), P800 (786 ± 24.2 μm), and P1000 (993 ± 26.0 μm) were produced by a 3D printer. Subsequently, the optimum pore size, the P600, for mechanical properties and osteogenesis was selected based on in vitro experiments. To improve the interfacial bioactivity of porous PEKK scaffolds, hydroxyapatite (HAp) crystals were generated via in situ biomimetic mineralization induced by the phase transited lysozyme (PTL) coating. Herein, a micro/nanostructured surface showing HAp crystals on PEKK scaffold was developed. In vitro and in vivo experiments confirmed that the porous PEKK-HAp scaffolds exhibited highly interconnected pores and functional surface structures that were favorable for biocompatibility and osteoinductivity, which boosted bone regeneration. Therefore, this work not only demonstrates that the pore structure of the P600 scaffold is suitable for PEKK orthopedic implants but also sheds light on a synergistic approach involving 3D printing and biomimetic mineralization, which has the potential to yield customized 3D PEKK-HAp scaffolds with enhanced osteoinductivity and osteogenesis, offering a promising strategy for bone tissue engineering.","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"22 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140151766","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Changqiang Wu, Wei Chen, Shuang Yan, Jie Zhong, Liang Du, Chenwu Yang, Yu Pu, Yang Li, Jiafu Lin, Mei Zeng, Xiaoming Zhang
Non-invasive image-guided precise photothermal/photodynamic therapy (PTT/PDT) has been proven an effective local treatment modality, but incompetent against metastases. Hence the combination of local PTT/PDT and systemic immunotherapy would be a promising strategy for tumor eradication. Herein, a MRI-visualized PTT/PDT agent (SIDP NMs) was constructed, and the efficacy of its multimodal combination with PD-1 inhibitor in the treatment of melanoma and metastases was studied. Due to the hydrophobic encapsulation of indocyanine green (ICG) within the micellar core, SIDP NMs exhibited excellent photothermal/photodynamic properties and stability under 808 nm near-infrared laser (NIR). In vitro cell experiments showed that SIDP NMs had a good killing effect. After incubating with B16-F10 cells for 24 h and irradiating with 808 nm laser for 10 min, cell viability decreased significantly. Magnetic resonance imaging experiments in melanoma-bearing mice have shown that the dynamic distribution of SIDP NMs in tumor tissue could be monitored by T2WI and T2-MAP noninvasively due to the presence of superparamagnetic iron oxide nanocrystal (SPIO) in SIDP NMs. When the 808 nm laser was irradiated at the maximum focusing time point shown by MRI, the temperature of the tumor area rapidly increased from 32 °C to 60.7 °C in five minutes. In mouse melanoma ablation and distant tumor immunotherapy studies, SIDP NMs provided excellent MRI-guided photothermal/photodynamic therapy results and, when combined with PD-1 inhibitor, have great potential to cure primary tumors and eradicate metastases.
{"title":"MRI-guided photothermal/photodynamic immune activation combined with PD-1 inhibitor for the multimodal combination therapy of melanoma and metastases","authors":"Changqiang Wu, Wei Chen, Shuang Yan, Jie Zhong, Liang Du, Chenwu Yang, Yu Pu, Yang Li, Jiafu Lin, Mei Zeng, Xiaoming Zhang","doi":"10.1093/rb/rbae019","DOIUrl":"https://doi.org/10.1093/rb/rbae019","url":null,"abstract":"Non-invasive image-guided precise photothermal/photodynamic therapy (PTT/PDT) has been proven an effective local treatment modality, but incompetent against metastases. Hence the combination of local PTT/PDT and systemic immunotherapy would be a promising strategy for tumor eradication. Herein, a MRI-visualized PTT/PDT agent (SIDP NMs) was constructed, and the efficacy of its multimodal combination with PD-1 inhibitor in the treatment of melanoma and metastases was studied. Due to the hydrophobic encapsulation of indocyanine green (ICG) within the micellar core, SIDP NMs exhibited excellent photothermal/photodynamic properties and stability under 808 nm near-infrared laser (NIR). In vitro cell experiments showed that SIDP NMs had a good killing effect. After incubating with B16-F10 cells for 24 h and irradiating with 808 nm laser for 10 min, cell viability decreased significantly. Magnetic resonance imaging experiments in melanoma-bearing mice have shown that the dynamic distribution of SIDP NMs in tumor tissue could be monitored by T2WI and T2-MAP noninvasively due to the presence of superparamagnetic iron oxide nanocrystal (SPIO) in SIDP NMs. When the 808 nm laser was irradiated at the maximum focusing time point shown by MRI, the temperature of the tumor area rapidly increased from 32 °C to 60.7 °C in five minutes. In mouse melanoma ablation and distant tumor immunotherapy studies, SIDP NMs provided excellent MRI-guided photothermal/photodynamic therapy results and, when combined with PD-1 inhibitor, have great potential to cure primary tumors and eradicate metastases.","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"112 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-03-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140150952","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Wound repair is a complex physiological process that often leads to bacterial infections, which significantly threaten human health. Therefore, developing wound-healing materials that promote healing and prevent bacterial infections is crucial. In this study, the coordination interaction between sulfhydryl groups on dithiothreitol (DTT) and MoS2 nanosheets is investigated to synthesize a MoS2-DTT nanozyme with photothermal properties and an improved free-radical scavenging ability. Double-bond-modified hyaluronic acid is used as a monomer and is cross-linked with a PF127-DA agent. PHMoD is prepared in coordination with MoS2-dithiothreitol as the functional component. This hydrogel exhibits antioxidant and antibacterial properties, attributed to the catalytic activity of catalase-like enzymes and photothermal effects. Under the NIR, it exhibits potent antibacterial effects against gram-positive (Staphylococcus aureus) and gram-negative bacteria (Escherichia coli), achieving bactericidal rates of 99.76% and 99.42%, respectively. Furthermore, the hydrogel exhibits remarkable ROS scavenging and antioxidant capabilities, effectively countering oxidative stress in L929 cells. Remarkably, in an animal model, wounds treated with the PHMoD(2.0) and NIR laser heal the fastest, sealing completely within 10 d. These results indicate the unique biocompatibility and bifunctionality of the PHMoD, which make it a promising material for wound-healing applications.
{"title":"Antibacterial and antioxidant bifunctional hydrogel based on hyaluronic acid complex MoS2-dithiothreitol nanozyme for treatment of infected wounds","authors":"Yongping Lu, Weiqi Kang, Yue Yu, Ling Liang, Jinrong Li, Haiying Lu, Ping Shi, Mingfang He, Yuemin Wang, Jianshu Li, Xingyu Chen","doi":"10.1093/rb/rbae025","DOIUrl":"https://doi.org/10.1093/rb/rbae025","url":null,"abstract":"Wound repair is a complex physiological process that often leads to bacterial infections, which significantly threaten human health. Therefore, developing wound-healing materials that promote healing and prevent bacterial infections is crucial. In this study, the coordination interaction between sulfhydryl groups on dithiothreitol (DTT) and MoS2 nanosheets is investigated to synthesize a MoS2-DTT nanozyme with photothermal properties and an improved free-radical scavenging ability. Double-bond-modified hyaluronic acid is used as a monomer and is cross-linked with a PF127-DA agent. PHMoD is prepared in coordination with MoS2-dithiothreitol as the functional component. This hydrogel exhibits antioxidant and antibacterial properties, attributed to the catalytic activity of catalase-like enzymes and photothermal effects. Under the NIR, it exhibits potent antibacterial effects against gram-positive (Staphylococcus aureus) and gram-negative bacteria (Escherichia coli), achieving bactericidal rates of 99.76% and 99.42%, respectively. Furthermore, the hydrogel exhibits remarkable ROS scavenging and antioxidant capabilities, effectively countering oxidative stress in L929 cells. Remarkably, in an animal model, wounds treated with the PHMoD(2.0) and NIR laser heal the fastest, sealing completely within 10 d. These results indicate the unique biocompatibility and bifunctionality of the PHMoD, which make it a promising material for wound-healing applications.","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"26 1","pages":""},"PeriodicalIF":6.7,"publicationDate":"2024-03-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140098271","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}