A biomechanical environment constructed exploiting the mechanical property of the extracellular matrix and external loading is essential for cell behaviour. Building suitable mechanical stimuli using feasible scaffold material and moderate mechanical loading is critical in bone tissue engineering for bone repair. However, the detailed mechanism of the mechanical regulation remains ambiguous. In addition, TRPV4 is involved in bone development. Therefore, this study aims to construct a viscoelastic hydrogel combined with dynamic compressive loading and investigate the effect of the dynamic mechanical environment on the osteogenic differentiation of stem cells and bone repair in vivo. The role of TRPV4 in the mechanobiology process was also assessed. A sodium alginate-gelatine hydrogel with adjustable viscoelasticity and good cell adhesion ability was obtained. The osteogenic differentiation of BMSCs was obtained using the fast stress relaxation hydrogel and a smaller compression strain of 1.5%. TRPV4 was activated in the hydrogel with fast stress relaxation time, followed by the increase in intracellular Ca2+ level and the activation of the Wnt/β-catenin pathway. The inhibition of TRPV4 induced a decrease in the intracellular Ca2+ level, down-regulation of β-catenin and reduced osteogenesis differentiation of BMSCs, suggesting that TRPV4 might be the key mechanism in the regulation of BMSC osteogenic differentiation in the viscoelastic dynamic mechanical environment. The fast stress relaxation hydrogel also showed a good osteogenic promotion effect in the rat femoral defect model. The dynamic viscoelastic mechanical environment significantly induced the osteogenic differentiation of BMSCs and bone regeneration, which TRPV4 being involved in this mechanobiological process. Our study not only provided important guidance for the mechanical design of new biomaterials, but also provided a new perspective for the understanding of the interaction between cells and materials, the role of mechanical loading in tissue regeneration and the use of mechanical regulation in tissue engineering.
{"title":"Viscoelastic hydrogel combined with dynamic compression promotes osteogenic differentiation of bone marrow mesenchymal stem cells and bone repair in rats.","authors":"Chao Yang, Wenbin Cai, Pan Xiang, Yu Liu, Hao Xu, Wen Zhang, Fengxuan Han, Zongping Luo, Ting Liang","doi":"10.1093/rb/rbae136","DOIUrl":"10.1093/rb/rbae136","url":null,"abstract":"<p><p>A biomechanical environment constructed exploiting the mechanical property of the extracellular matrix and external loading is essential for cell behaviour. Building suitable mechanical stimuli using feasible scaffold material and moderate mechanical loading is critical in bone tissue engineering for bone repair. However, the detailed mechanism of the mechanical regulation remains ambiguous. In addition, TRPV4 is involved in bone development. Therefore, this study aims to construct a viscoelastic hydrogel combined with dynamic compressive loading and investigate the effect of the dynamic mechanical environment on the osteogenic differentiation of stem cells and bone repair <i>in vivo</i>. The role of TRPV4 in the mechanobiology process was also assessed. A sodium alginate-gelatine hydrogel with adjustable viscoelasticity and good cell adhesion ability was obtained. The osteogenic differentiation of BMSCs was obtained using the fast stress relaxation hydrogel and a smaller compression strain of 1.5%. TRPV4 was activated in the hydrogel with fast stress relaxation time, followed by the increase in intracellular Ca<sup>2+</sup> level and the activation of the Wnt/β-catenin pathway. The inhibition of TRPV4 induced a decrease in the intracellular Ca<sup>2+</sup> level, down-regulation of β-catenin and reduced osteogenesis differentiation of BMSCs, suggesting that TRPV4 might be the key mechanism in the regulation of BMSC osteogenic differentiation in the viscoelastic dynamic mechanical environment. The fast stress relaxation hydrogel also showed a good osteogenic promotion effect in the rat femoral defect model. The dynamic viscoelastic mechanical environment significantly induced the osteogenic differentiation of BMSCs and bone regeneration, which TRPV4 being involved in this mechanobiological process. Our study not only provided important guidance for the mechanical design of new biomaterials, but also provided a new perspective for the understanding of the interaction between cells and materials, the role of mechanical loading in tissue regeneration and the use of mechanical regulation in tissue engineering.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"12 ","pages":"rbae136"},"PeriodicalIF":5.6,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751691/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143024244","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 : 2024-11-23eCollection Date: 2025-01-01DOI: 10.1093/rb/rbae134
Zhixian Yuan, Wei Zhang, Chang Wang, Chuwei Zhang, Chao Hu, Lu Liu, Lunli Xiang, Shun Yao, Rong Shi, Dejiang Fan, Bibo Ren, Gaoxing Luo, Jun Deng
Chronic diabetic wounds present significant treatment challenges due to their complex microenvironment, often leading to suboptimal healing outcomes. Hydrogen sulfide (H2S), a crucial gaseous signaling molecule, has shown great potential in modulating inflammation, oxidative stress and extracellular matrix remodeling, which are essential for effective wound healing. However, conventional H2S delivery systems lack the adaptability required to meet the dynamic demands of different healing stages, thereby limiting their therapeutic efficacy. To address this, we developed an injectable, ROS-responsive H2S donor system integrated within a gelatin methacryloyl (GelMA) hydrogel matrix, forming a double-network hydrogel (GelMA-ODex@RRHD). The injectability of this hydrogel allows for minimally invasive application, conforming closely to wound contours and ensuring uniform distribution. The incorporation of oxidatively modified dextran derivatives (ODex) not only preserves biocompatibility but also enables the chemical attachment of ROS-responsive H2S donors. The GelMA-ODex@RRHD hydrogel releases H2S in response to oxidative stress, optimizing the environment for cell growth, modulating macrophage polarization and supporting vascular regeneration. This innovative material effectively suppresses inflammation during the initial phase, promotes tissue regeneration in the proliferative phase and facilitates controlled matrix remodeling in later stages, ultimately enhancing wound closure and functional recovery. The H2S released by GelMA-ODex@RRHD not only expedited the process of wound healing but also improved the biomechanical characteristics of newborn skin in diabetic mice, particularly in terms of stiffness and elasticity. This enhancement resulted in the skin quality being more similar to normal skin during the wound healing process. By aligning therapeutic delivery with the natural healing process, this approach offers a promising pathway toward more effective and personalized treatments for chronic diabetic wounds.
{"title":"A microenvironment-adaptive GelMA-ODex@RRHD hydrogel for responsive release of H<sub>2</sub>S in promoted chronic diabetic wound repair.","authors":"Zhixian Yuan, Wei Zhang, Chang Wang, Chuwei Zhang, Chao Hu, Lu Liu, Lunli Xiang, Shun Yao, Rong Shi, Dejiang Fan, Bibo Ren, Gaoxing Luo, Jun Deng","doi":"10.1093/rb/rbae134","DOIUrl":"https://doi.org/10.1093/rb/rbae134","url":null,"abstract":"<p><p>Chronic diabetic wounds present significant treatment challenges due to their complex microenvironment, often leading to suboptimal healing outcomes. Hydrogen sulfide (H<sub>2</sub>S), a crucial gaseous signaling molecule, has shown great potential in modulating inflammation, oxidative stress and extracellular matrix remodeling, which are essential for effective wound healing. However, conventional H<sub>2</sub>S delivery systems lack the adaptability required to meet the dynamic demands of different healing stages, thereby limiting their therapeutic efficacy. To address this, we developed an injectable, ROS-responsive H<sub>2</sub>S donor system integrated within a gelatin methacryloyl (GelMA) hydrogel matrix, forming a double-network hydrogel (GelMA-ODex@RRHD). The injectability of this hydrogel allows for minimally invasive application, conforming closely to wound contours and ensuring uniform distribution. The incorporation of oxidatively modified dextran derivatives (ODex) not only preserves biocompatibility but also enables the chemical attachment of ROS-responsive H<sub>2</sub>S donors. The GelMA-ODex@RRHD hydrogel releases H<sub>2</sub>S in response to oxidative stress, optimizing the environment for cell growth, modulating macrophage polarization and supporting vascular regeneration. This innovative material effectively suppresses inflammation during the initial phase, promotes tissue regeneration in the proliferative phase and facilitates controlled matrix remodeling in later stages, ultimately enhancing wound closure and functional recovery. The H<sub>2</sub>S released by GelMA-ODex@RRHD not only expedited the process of wound healing but also improved the biomechanical characteristics of newborn skin in diabetic mice, particularly in terms of stiffness and elasticity. This enhancement resulted in the skin quality being more similar to normal skin during the wound healing process. By aligning therapeutic delivery with the natural healing process, this approach offers a promising pathway toward more effective and personalized treatments for chronic diabetic wounds.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"12 ","pages":"rbae134"},"PeriodicalIF":5.6,"publicationDate":"2024-11-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953029","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}
Nerve injuries can be tantamount to severe impairment, standard treatment such as the use of autograft or surgery comes with complications and confers a shortened relief. The mechanism relevant to the regeneration of the optic nerve seems yet to be fully uncovered. The prevailing rate of vision loss as a result of direct or indirect insult on the optic nerve is alarming. Currently, the use of nerve guide conduits (NGC) to some extent has proven reliable especially in rodents and among the peripheral nervous system, a promising ground for regeneration and functional recovery, however in the optic nerve, this NGC function seems quite unfamous. The insufficient NGC application and the unabridged regeneration of the optic nerve could be a result of the limited information on cellular and molecular activities. This review seeks to tackle two major factors (i) the cellular and molecular activity involved in traumatic optic neuropathy and (ii) the NGC application for the optic nerve regeneration. The understanding of cellular and molecular concepts encompassed, ocular inflammation, extrinsic signaling and intrinsic signaling for axon growth, mobile zinc role, Ca2+ factor associated with the optic nerve, alternative therapies from nanotechnology based on the molecular information and finally the nanotechnological outlook encompassing applicable biomaterials and the use of NGC for regeneration. The challenges and future outlook regarding optic nerve regenerations are also discussed. Upon the many approaches used, the comprehensive role of the cellular and molecular mechanism may set grounds for the efficient application of the NGC for optic nerve regeneration.
{"title":"Engineered bio-functional material-based nerve guide conduits for optic nerve regeneration: a view from the cellular perspective, challenges and the future outlook.","authors":"Enoch Obeng, Baoguo Shen, Wei Wang, Zhenyuan Xie, Wenyi Zhang, Zhixing Li, Qinqin Yao, Wencan Wu","doi":"10.1093/rb/rbae133","DOIUrl":"https://doi.org/10.1093/rb/rbae133","url":null,"abstract":"<p><p>Nerve injuries can be tantamount to severe impairment, standard treatment such as the use of autograft or surgery comes with complications and confers a shortened relief. The mechanism relevant to the regeneration of the optic nerve seems yet to be fully uncovered. The prevailing rate of vision loss as a result of direct or indirect insult on the optic nerve is alarming. Currently, the use of nerve guide conduits (NGC) to some extent has proven reliable especially in rodents and among the peripheral nervous system, a promising ground for regeneration and functional recovery, however in the optic nerve, this NGC function seems quite unfamous. The insufficient NGC application and the unabridged regeneration of the optic nerve could be a result of the limited information on cellular and molecular activities. This review seeks to tackle two major factors (i) the cellular and molecular activity involved in traumatic optic neuropathy and (ii) the NGC application for the optic nerve regeneration. The understanding of cellular and molecular concepts encompassed, ocular inflammation, extrinsic signaling and intrinsic signaling for axon growth, mobile zinc role, Ca<sup>2+</sup> factor associated with the optic nerve, alternative therapies from nanotechnology based on the molecular information and finally the nanotechnological outlook encompassing applicable biomaterials and the use of NGC for regeneration. The challenges and future outlook regarding optic nerve regenerations are also discussed. Upon the many approaches used, the comprehensive role of the cellular and molecular mechanism may set grounds for the efficient application of the NGC for optic nerve regeneration.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"12 ","pages":"rbae133"},"PeriodicalIF":5.6,"publicationDate":"2024-11-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703557/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953931","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 : 2024-11-21eCollection Date: 2025-01-01DOI: 10.1093/rb/rbae135
Chenguang Liu, Jingjie Gao, Yuying Cheng, Shanshan Zhang, Caiyun Fu
Low tumor enrichment remains a serious and urgent problem for drug delivery in cancer therapy. Accurate targeting of tumor sites is still a critical aim in cancer therapy. Though there have been a variety of delivery strategies to improve the tumor targeting and enrichment, biological barriers still cause most delivered guests to fail or be excreted before they work. Recently, cell membrane-based systems have attracted a huge amount of attention due to their advantages such as easy access, good biocompatibility and immune escape, which contribute to their biomimetic structures and specific surface proteins. Furthermore, cancer cell membrane-based delivery systems are referred to as homologous-targeting function in which they exhibit significantly high adhesion and internalization to homologous-type tumor sites or cells even though the exact mechanism is not entirely revealed. Here, we summarize the sources and characterizations of cancer cell membrane systems, including reconstructed single or hybrid membrane-based nano-/microcarriers, as well as engineered cancer cells. Additionally, advanced applications of these cancer cell membrane systems in cancer therapy are categorized and summarized according to the components of membranes. The potential factors related to homologous targeting of cancer cell membrane-based systems are also discussed. By discussing the applications, challenges and opportunities, we expect the cancer cell membrane-based homologous-targeting systems to have a far-reaching development in preclinic or clinics.
{"title":"Homologous-adhering/targeting cell membrane- and cell-mediated delivery systems: a cancer-catch-cancer strategy in cancer therapy.","authors":"Chenguang Liu, Jingjie Gao, Yuying Cheng, Shanshan Zhang, Caiyun Fu","doi":"10.1093/rb/rbae135","DOIUrl":"10.1093/rb/rbae135","url":null,"abstract":"<p><p>Low tumor enrichment remains a serious and urgent problem for drug delivery in cancer therapy. Accurate targeting of tumor sites is still a critical aim in cancer therapy. Though there have been a variety of delivery strategies to improve the tumor targeting and enrichment, biological barriers still cause most delivered guests to fail or be excreted before they work. Recently, cell membrane-based systems have attracted a huge amount of attention due to their advantages such as easy access, good biocompatibility and immune escape, which contribute to their biomimetic structures and specific surface proteins. Furthermore, cancer cell membrane-based delivery systems are referred to as homologous-targeting function in which they exhibit significantly high adhesion and internalization to homologous-type tumor sites or cells even though the exact mechanism is not entirely revealed. Here, we summarize the sources and characterizations of cancer cell membrane systems, including reconstructed single or hybrid membrane-based nano-/microcarriers, as well as engineered cancer cells. Additionally, advanced applications of these cancer cell membrane systems in cancer therapy are categorized and summarized according to the components of membranes. The potential factors related to homologous targeting of cancer cell membrane-based systems are also discussed. By discussing the applications, challenges and opportunities, we expect the cancer cell membrane-based homologous-targeting systems to have a far-reaching development in preclinic or clinics.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"12 ","pages":"rbae135"},"PeriodicalIF":5.6,"publicationDate":"2024-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11729729/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142984651","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 : 2024-11-19eCollection Date: 2024-01-01DOI: 10.1093/rb/rbae132
[This corrects the article DOI: 10.1093/rb/rbad014.].
[此处更正了文章 DOI:10.1093/rb/rbad014]。
{"title":"Correction to: Nanocarrier of Pin1 inhibitor based on supercritical fluid technology inhibits cancer metastasis by blocking multiple signaling pathways.","authors":"","doi":"10.1093/rb/rbae132","DOIUrl":"https://doi.org/10.1093/rb/rbae132","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/rb/rbad014.].</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"11 ","pages":"rbae132"},"PeriodicalIF":5.6,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11576348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682677","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}
Alveolar ridge loss presents difficulties for implant placement and stability. To address this, alveolar ridge preservation (ARP) is required to maintain bone and avoid the need for ridge augmentation using socket grafting. In this study, a scaffold for ARP was created by fabricating a 3D porous dense microfiber silk fibroin (mSF) embedded in poly(vinyl alcohol) (PVA), which mimics the osteoid template. The research utilized a freeze-thawing technique to create a mimicked osteoid 3D porous scaffold by incorporating different amounts of mSF into the PVA, namely, 1%, 3%, 5% and 7%. Subsequently, a 3D profilometer machine and a scanning electron microscope were employed to examine the morphology and size of the mSF and the mimicked osteoid 3D porous scaffold in all groups. Thermal characteristics and crystalline structure were analyzed before assessing the water contact angle, swelling behavior, degradation and mechanical properties. The experiment evaluated the biological performance of the mimicked osteoid 3D porous scaffold by examining the efficacy of osteoblast cell adhesion, proliferation, viability, protein synthesis, alkaline phosphatase (ALP) activity and calcium synthesis. Finally, the ability of osteoblast cells to regulate the osteoid matrix deposition on the osteoid 3D porous scaffold was assessed by mimicking the dynamic bone environment using rat mesenchymal stem cells. The findings suggest that incorporating mSF into PVA enhances the interconnective pore size, crystalline structure and thermal behavior of the mimicked osteoid 3D porous scaffold. The hydrophilicity of PVA decreased with an increase in the proportion of mSF, while a higher proportion of mSF resulted in increased swelling and mechanical characteristics. Incorporating a greater proportion of mSF, specifically 5% and 7%, led to a reduced rate of degradation. The addition of 5% mSF to the PVA 3D porous scaffold resulted in remarkable biological properties and excellent osteoconductive activity.
{"title":"Mimicking osteoid 3D porous dense microfiber silk fibroin embedded poly(vinyl alcohol) scaffold for alveolar ridge preservation.","authors":"Supaporn Sangkert, Perumal Ramesh Kannan, Jirut Meesane, Kanokporn Santavalimp, Jutharat Phongthanawarakun, Walaiporn Promkaew, Wachiratan Anupan, Nuttawut Thuaksuban","doi":"10.1093/rb/rbae130","DOIUrl":"10.1093/rb/rbae130","url":null,"abstract":"<p><p>Alveolar ridge loss presents difficulties for implant placement and stability. To address this, alveolar ridge preservation (ARP) is required to maintain bone and avoid the need for ridge augmentation using socket grafting. In this study, a scaffold for ARP was created by fabricating a 3D porous dense microfiber silk fibroin (mSF) embedded in poly(vinyl alcohol) (PVA), which mimics the osteoid template. The research utilized a freeze-thawing technique to create a mimicked osteoid 3D porous scaffold by incorporating different amounts of mSF into the PVA, namely, 1%, 3%, 5% and 7%. Subsequently, a 3D profilometer machine and a scanning electron microscope were employed to examine the morphology and size of the mSF and the mimicked osteoid 3D porous scaffold in all groups. Thermal characteristics and crystalline structure were analyzed before assessing the water contact angle, swelling behavior, degradation and mechanical properties. The experiment evaluated the biological performance of the mimicked osteoid 3D porous scaffold by examining the efficacy of osteoblast cell adhesion, proliferation, viability, protein synthesis, alkaline phosphatase (ALP) activity and calcium synthesis. Finally, the ability of osteoblast cells to regulate the osteoid matrix deposition on the osteoid 3D porous scaffold was assessed by mimicking the dynamic bone environment using rat mesenchymal stem cells. The findings suggest that incorporating mSF into PVA enhances the interconnective pore size, crystalline structure and thermal behavior of the mimicked osteoid 3D porous scaffold. The hydrophilicity of PVA decreased with an increase in the proportion of mSF, while a higher proportion of mSF resulted in increased swelling and mechanical characteristics. Incorporating a greater proportion of mSF, specifically 5% and 7%, led to a reduced rate of degradation. The addition of 5% mSF to the PVA 3D porous scaffold resulted in remarkable biological properties and excellent osteoconductive activity.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"12 ","pages":"rbae130"},"PeriodicalIF":5.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11725345/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142972112","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 : 2024-11-13eCollection Date: 2025-01-01DOI: 10.1093/rb/rbae131
Yage Sun, Xinrui Zhao, Qian Zhang, Rong Yang, Wenguang Liu
The hypoxia microenvironment post-myocardial infarction (MI) critically disturbs cellular metabolism and inflammation response, leading to scarce bioenergy supplying, prolonged inflammatory phase and high risk of cardiac fibrosis during cardiac restoration. Herein, an injectable hydrogel is prepared by Schiff base reaction between fructose-1,6-bisphosphate (FBP)-grafted carboxymethyl chitosan (CF) and oxidized dextran (OD), followed by loading fucoidan-coated baicalin (BA)-encapsulated zein nanoparticles (BFZ NPs), in which immunoregulatory and metabolism improving functions are integrally included. The grafted FBP serves to enhance glycolysis and provide more bioenergy for cardiomyocytes survival under hypoxia microenvironment, and elevating cellular antioxidant capacity via pentose phosphate pathway. OD with intrinsic anti-inflammatory effect can induce M2 polarization of macrophages to accelerate inflammatory elimination. While facing the possibility of endothelial-to-mesenchymal transition (EndoMT) caused by excessive expressed TGF-β1 secreted from M2 macrophages, BFZ NPs can target endothelia cells and intracellularly release BA to regulate the level of fatty acid oxidation, resulting in retained endothelial features and decreased risk of cardiac fibrosis. After being injecting the hydrogel into rats' infarcted cardiac, the 28-day-post surgical outcomes demonstrate its benign effects on restoring cardiac functions and attenuating adverse left ventricular remodeling. This study shows a promising measure for MI treatment with immunoregulating and metabolism regulation comprehensively.
{"title":"An immunoregulatory and metabolism-improving injectable hydrogel for cardiac repair after myocardial infarction.","authors":"Yage Sun, Xinrui Zhao, Qian Zhang, Rong Yang, Wenguang Liu","doi":"10.1093/rb/rbae131","DOIUrl":"https://doi.org/10.1093/rb/rbae131","url":null,"abstract":"<p><p>The hypoxia microenvironment post-myocardial infarction (MI) critically disturbs cellular metabolism and inflammation response, leading to scarce bioenergy supplying, prolonged inflammatory phase and high risk of cardiac fibrosis during cardiac restoration. Herein, an injectable hydrogel is prepared by Schiff base reaction between fructose-1,6-bisphosphate (FBP)-grafted carboxymethyl chitosan (CF) and oxidized dextran (OD), followed by loading fucoidan-coated baicalin (BA)-encapsulated zein nanoparticles (BFZ NPs), in which immunoregulatory and metabolism improving functions are integrally included. The grafted FBP serves to enhance glycolysis and provide more bioenergy for cardiomyocytes survival under hypoxia microenvironment, and elevating cellular antioxidant capacity <i>via</i> pentose phosphate pathway. OD with intrinsic anti-inflammatory effect can induce M2 polarization of macrophages to accelerate inflammatory elimination. While facing the possibility of endothelial-to-mesenchymal transition (EndoMT) caused by excessive expressed TGF-β1 secreted from M2 macrophages, BFZ NPs can target endothelia cells and intracellularly release BA to regulate the level of fatty acid oxidation, resulting in retained endothelial features and decreased risk of cardiac fibrosis. After being injecting the hydrogel into rats' infarcted cardiac, the 28-day-post surgical outcomes demonstrate its benign effects on restoring cardiac functions and attenuating adverse left ventricular remodeling. This study shows a promising measure for MI treatment with immunoregulating and metabolism regulation comprehensively.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"12 ","pages":"rbae131"},"PeriodicalIF":5.6,"publicationDate":"2024-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953514","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}
Nanohydroxyapatite (nHA) is distinguished by its exceptional biocompatibility, bioactivity and biodegradability, qualities attributed to its similarity to the mineral component of human bone. This review discusses the synthesis techniques of nHA, highlighting how these methods shape its physicochemical attributes and, in turn, its utility in biomedical applications. The versatility of nHA is further enhanced by doping with biologically significant ions like magnesium or zinc, which can improve its bioactivity and confer therapeutic properties. Notably, nHA-based composites, incorporating metal, polymeric and bioceramic scaffolds, exhibit enhanced osteoconductivity and osteoinductivity. In orthopedic field, nHA and its composites serve effectively as bone graft substitutes, showing exceptional osteointegration and vascularization capabilities. In dentistry, these materials contribute to enamel remineralization, mitigate tooth sensitivity and are employed in surface modification of dental implants. For cancer therapy, nHA composites offer a promising strategy to inhibit tumor growth while sparing healthy tissues. Furthermore, nHA-based composites are emerging as sophisticated platforms with high surface ratio for the delivery of drugs and bioactive substances, gradually releasing therapeutic agents for progressive treatment benefits. Overall, this review delineates the synthesis, modifications and applications of nHA in various biomedical fields, shed light on the future advancements in biomaterials research.
{"title":"Advancements in nanohydroxyapatite: synthesis, biomedical applications and composite developments.","authors":"Rui Zhao, Xiang Meng, Zixian Pan, Yongjia Li, Hui Qian, Xiangdong Zhu, Xiao Yang, Xingdong Zhang","doi":"10.1093/rb/rbae129","DOIUrl":"https://doi.org/10.1093/rb/rbae129","url":null,"abstract":"<p><p>Nanohydroxyapatite (nHA) is distinguished by its exceptional biocompatibility, bioactivity and biodegradability, qualities attributed to its similarity to the mineral component of human bone. This review discusses the synthesis techniques of nHA, highlighting how these methods shape its physicochemical attributes and, in turn, its utility in biomedical applications. The versatility of nHA is further enhanced by doping with biologically significant ions like magnesium or zinc, which can improve its bioactivity and confer therapeutic properties. Notably, nHA-based composites, incorporating metal, polymeric and bioceramic scaffolds, exhibit enhanced osteoconductivity and osteoinductivity. In orthopedic field, nHA and its composites serve effectively as bone graft substitutes, showing exceptional osteointegration and vascularization capabilities. In dentistry, these materials contribute to enamel remineralization, mitigate tooth sensitivity and are employed in surface modification of dental implants. For cancer therapy, nHA composites offer a promising strategy to inhibit tumor growth while sparing healthy tissues. Furthermore, nHA-based composites are emerging as sophisticated platforms with high surface ratio for the delivery of drugs and bioactive substances, gradually releasing therapeutic agents for progressive treatment benefits. Overall, this review delineates the synthesis, modifications and applications of nHA in various biomedical fields, shed light on the future advancements in biomaterials research.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"12 ","pages":"rbae129"},"PeriodicalIF":5.6,"publicationDate":"2024-11-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703556/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953159","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 : 2024-11-01eCollection Date: 2025-01-01DOI: 10.1093/rb/rbae127
Ying Fang, Yiran Han, Lu Yang, Ranjith Kumar Kankala, Shibin Wang, Aizheng Chen, Chaoping Fu
Conductive hydrogels (CHs) represent a burgeoning class of intelligent wound dressings, providing innovative strategies for chronic wound repair and monitoring. Notably, CHs excel in promoting cell migration and proliferation, exhibit powerful antibacterial and anti-inflammatory properties, and enhance collagen deposition and angiogenesis. These capabilities, combined with real-time monitoring functions, play a pivotal role in accelerating collagen synthesis, angiogenesis and continuous wound surveillance. This review delves into the preparation, mechanisms and applications of CHs in wound management, highlighting their diverse and significant advantages. It emphasizes the effectiveness of CHs in treating various chronic wounds, such as diabetic ulcers, infected wounds, temperature-related injuries and athletic joint wounds. Additionally, it explores the diverse applications of multifunctional intelligent CHs in advanced wound care technologies, encompassing self-powered dressings, electrically-triggered drug delivery, comprehensive diagnostics and therapeutics and scar-free healing. Furthermore, the review highlights the challenges to their broader implementation, explores the future of intelligent wound dressings and discusses the transformative role of CHs in chronic wound management, particularly in the context of the anticipated integration of artificial intelligence (AI). Additionally, this review underscores the challenges hindering the widespread adoption of CHs, delves into the prospects of intelligent wound dressings and elucidates the transformative impact of CHs in managing chronic wounds, especially with the forthcoming integration of AI. This integration promises to facilitate predictive analytics and tailor personalized treatment plans, thereby further refining the healing process and elevating patient satisfaction. Addressing these challenges and harnessing emerging technologies, we postulate, will establish CHs as a cornerstone in revolutionizing chronic wound care, significantly improving patient outcomes.
{"title":"Conductive hydrogels: intelligent dressings for monitoring and healing chronic wounds.","authors":"Ying Fang, Yiran Han, Lu Yang, Ranjith Kumar Kankala, Shibin Wang, Aizheng Chen, Chaoping Fu","doi":"10.1093/rb/rbae127","DOIUrl":"https://doi.org/10.1093/rb/rbae127","url":null,"abstract":"<p><p>Conductive hydrogels (CHs) represent a burgeoning class of intelligent wound dressings, providing innovative strategies for chronic wound repair and monitoring. Notably, CHs excel in promoting cell migration and proliferation, exhibit powerful antibacterial and anti-inflammatory properties, and enhance collagen deposition and angiogenesis. These capabilities, combined with real-time monitoring functions, play a pivotal role in accelerating collagen synthesis, angiogenesis and continuous wound surveillance. This review delves into the preparation, mechanisms and applications of CHs in wound management, highlighting their diverse and significant advantages. It emphasizes the effectiveness of CHs in treating various chronic wounds, such as diabetic ulcers, infected wounds, temperature-related injuries and athletic joint wounds. Additionally, it explores the diverse applications of multifunctional intelligent CHs in advanced wound care technologies, encompassing self-powered dressings, electrically-triggered drug delivery, comprehensive diagnostics and therapeutics and scar-free healing. Furthermore, the review highlights the challenges to their broader implementation, explores the future of intelligent wound dressings and discusses the transformative role of CHs in chronic wound management, particularly in the context of the anticipated integration of artificial intelligence (AI). Additionally, this review underscores the challenges hindering the widespread adoption of CHs, delves into the prospects of intelligent wound dressings and elucidates the transformative impact of CHs in managing chronic wounds, especially with the forthcoming integration of AI. This integration promises to facilitate predictive analytics and tailor personalized treatment plans, thereby further refining the healing process and elevating patient satisfaction. Addressing these challenges and harnessing emerging technologies, we postulate, will establish CHs as a cornerstone in revolutionizing chronic wound care, significantly improving patient outcomes.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"12 ","pages":"rbae127"},"PeriodicalIF":5.6,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11703555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142953558","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}
Biomineralization-based cell-material living composites ex vivo showed great potential for living materials construction and cell regulation. However, cells in scaffolds with unconnected pores usually induce confined nutrient transfer and cell-cell communications, affecting the transformation of osteoblasts into osteocytes and the mineralization process. Herein, the osteoblast-materials living hybrids were constructed with porous PLLA microspheres using a rational design, in which cell-based living materials presented an improved osteoblast differentiation and mineralization model using rationally designed cell-microsphere composites. The results indicated that the microfluidic-based technique provided an efficient and highly controllable approach for producing on-demand PLLA microspheres with tiny pores (<5 μm), medium pores (5-15 μm) and large pores (>15 μm), as well as further drug delivery. Furthermore, the simvastatin (SIM)-loaded porous PLLA microsphere with ε-polylysine (ε-PL) modification was used for osteoblast (MC3T3-E1) implantation, achieving the cell-material living microhybrids, and the results demonstrated the ε-PL surface modification and SIM could improve osteoblast behavior regulation, including cell adhesion, proliferation, as well as the antibacterial effects. Both in vitro and in vivo results significantly demonstrated further cell proliferation, differentiation and cascade mineralization regulation. Then, the quantitative polymerase chain reaction or histological staining of typical markers, including collagen type I, alkaline phosphatase, runt-related transcription factor 2 and bone morphogenetic protein 2, as well as the calcium mineral deposition staining in situ, reconfirmed the transformation of osteoblasts into osteocytes. These achievements revealed a promising boost in osteogenesis toward mineralization at the microtissue level by cell-microsphere integration, suggesting an alternative strategy for materials-based ex vivo tissue construction and cell regulation, further demonstrating excellent application prospects in the field of biomineralization-based tissue regeneration.
基于生物矿化的体外细胞-材料活复合材料在活材料构建和细胞调控方面显示出巨大潜力。然而,未连通孔隙的支架中的细胞通常会导致营养物质传递和细胞间通讯受限,影响成骨细胞向骨细胞的转化和矿化过程。本文利用合理设计的细胞-微球复合材料,用多孔聚乳酸微球构建了成骨细胞-材料活体混合体,其中基于细胞的活体材料展示了一种改进的成骨细胞分化和矿化模型。结果表明,基于微流体的技术为按需生产具有微孔(15 μm)的聚乳酸微球以及进一步的药物输送提供了一种高效且高度可控的方法。结果表明ε-PL表面修饰和SIM能改善成骨细胞的行为调控,包括细胞粘附、增殖和抗菌作用。体外和体内研究结果均显著表明,细胞增殖、分化和级联矿化调控能力得到进一步提高。然后,典型标志物的定量聚合酶链反应或组织学染色,包括胶原 I 型、碱性磷酸酶、runt 相关转录因子 2 和骨形态发生蛋白 2,以及钙矿物质原位沉积染色,再次证实了成骨细胞向骨细胞的转化。这些成果揭示了通过细胞-微球整合在微组织水平促进成骨向矿化方向发展的前景,为基于材料的体外组织构建和细胞调控提供了另一种策略,进一步展示了在基于生物矿化的组织再生领域的良好应用前景。
{"title":"Cell-microsphere based living microhybrids for osteogenesis regulating to boosting biomineralization.","authors":"Zhaofan Hu, Yunyang Zhang, Jingjing Zhang, Ran Zheng, Yang Yang, Fei Kong, Haoran Li, Xinyan Yang, Shuhui Yang, Xiangdong Kong, Ruibo Zhao","doi":"10.1093/rb/rbae125","DOIUrl":"10.1093/rb/rbae125","url":null,"abstract":"<p><p>Biomineralization-based cell-material living composites <i>ex vivo</i> showed great potential for living materials construction and cell regulation. However, cells in scaffolds with unconnected pores usually induce confined nutrient transfer and cell-cell communications, affecting the transformation of osteoblasts into osteocytes and the mineralization process. Herein, the osteoblast-materials living hybrids were constructed with porous PLLA microspheres using a rational design, in which cell-based living materials presented an improved osteoblast differentiation and mineralization model using rationally designed cell-microsphere composites. The results indicated that the microfluidic-based technique provided an efficient and highly controllable approach for producing on-demand PLLA microspheres with tiny pores (<5 μm), medium pores (5-15 μm) and large pores (>15 μm), as well as further drug delivery. Furthermore, the simvastatin (SIM)-loaded porous PLLA microsphere with ε-polylysine (ε-PL) modification was used for osteoblast (MC3T3-E1) implantation, achieving the cell-material living microhybrids, and the results demonstrated the ε-PL surface modification and SIM could improve osteoblast behavior regulation, including cell adhesion, proliferation, as well as the antibacterial effects. Both <i>in vitro</i> and <i>in vivo</i> results significantly demonstrated further cell proliferation, differentiation and cascade mineralization regulation. Then, the quantitative polymerase chain reaction or histological staining of typical markers, including collagen type I, alkaline phosphatase, runt-related transcription factor 2 and bone morphogenetic protein 2, as well as the calcium mineral deposition staining <i>in situ</i>, reconfirmed the transformation of osteoblasts into osteocytes. These achievements revealed a promising boost in osteogenesis toward mineralization at the microtissue level by cell-microsphere integration, suggesting an alternative strategy for materials-based <i>ex vivo</i> tissue construction and cell regulation, further demonstrating excellent application prospects in the field of biomineralization-based tissue regeneration.</p>","PeriodicalId":20929,"journal":{"name":"Regenerative Biomaterials","volume":"11 ","pages":"rbae125"},"PeriodicalIF":5.6,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11578599/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142682672","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}