Pub Date : 2025-02-26DOI: 10.1016/j.bioactmat.2025.02.031
Qiongjun Zhu , Zhezhe Chen , Dan'an Wang , Xiaolu Jiao , Yi Luan , Min Wang , Rifang Luo , Yunbing Wang , Guosheng Fu , Yanan Wang , Wenbin Zhang
Early coagulation-inflammation interaction and late in-stent restenosis undermine the efficacy of vascular stents after implantation. Targeting the interplay between inflammation and coagulation, and smooth muscle cell (SMC) proliferation, we presented a microenvironment-responsive coating designed to regulate tissue responses and vascular regeneration throughout the remodeling process. Coagulation was inhibited by incorporating anticoagulant tirofiban into the coating. MMP9-responsive nanoparticles embedded in the coating released salvianolic acid A to modulate inflammatory cell behavior and inhibit SMC dysfunction. By effectively interfering with clotting and inflammation, the coating suppressed platelet-fibrin interaction and formation of platelet-monocyte aggregates, thereby mitigating adverse effects on reendothelialization. Its ability to influence SMC proliferation and migration resulted in reduced intimal hyperplasia. Coated stents were shown to significantly regulate tissue regeneration, improve the vascular environment and even reduced the lipid content in the narrowed atherosclerotic vessels in vivo. This direct approach enhanced the vascular tissue regeneration after stent implantation, and offered promising insights for optimizing vascular stent design.
{"title":"Microenvironment-responsive coating for vascular stents to regulate coagulation-inflammation interaction and promote vascular recovery","authors":"Qiongjun Zhu , Zhezhe Chen , Dan'an Wang , Xiaolu Jiao , Yi Luan , Min Wang , Rifang Luo , Yunbing Wang , Guosheng Fu , Yanan Wang , Wenbin Zhang","doi":"10.1016/j.bioactmat.2025.02.031","DOIUrl":"10.1016/j.bioactmat.2025.02.031","url":null,"abstract":"<div><div>Early coagulation-inflammation interaction and late in-stent restenosis undermine the efficacy of vascular stents after implantation. Targeting the interplay between inflammation and coagulation, and smooth muscle cell (SMC) proliferation, we presented a microenvironment-responsive coating designed to regulate tissue responses and vascular regeneration throughout the remodeling process. Coagulation was inhibited by incorporating anticoagulant tirofiban into the coating. MMP9-responsive nanoparticles embedded in the coating released salvianolic acid A to modulate inflammatory cell behavior and inhibit SMC dysfunction. By effectively interfering with clotting and inflammation, the coating suppressed platelet-fibrin interaction and formation of platelet-monocyte aggregates, thereby mitigating adverse effects on reendothelialization. Its ability to influence SMC proliferation and migration resulted in reduced intimal hyperplasia. Coated stents were shown to significantly regulate tissue regeneration, improve the vascular environment and even reduced the lipid content in the narrowed atherosclerotic vessels <em>in viv</em>o. This direct approach enhanced the vascular tissue regeneration after stent implantation, and offered promising insights for optimizing vascular stent design.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 443-457"},"PeriodicalIF":18.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487045","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 : 2025-02-26DOI: 10.1016/j.bioactmat.2025.01.036
Wei Sun , Hongwei Wu , Yiyang Yan , Xianzhu Zhang , Xudong Yao , Rui Li , Jingyi Zuo , Wenyue Li , Hongwei Ouyang
The reconstruction of large osteoarticular defects caused by tumor resection or severe trauma remains a clinical challenge. Current metal prostheses exhibit a lack of osteo-chondrogenic functionality and demonstrate poor integration with host tissues. This often results in complications such as abnormal bone absorption and prosthetic loosening, which may necessitate secondary revisions. Here, we propose a paradigm-shifting “living prosthesis” strategy that combines a customized 3D-printed hollow titanium humeral prosthesis with engineered bone marrow condensations presenting bone morphogenetic protein-2 (BMP-2) and transforming growth factor–β3 (TGF-β3) from encapsulated silk fibroin hydrogels. This innovative approach promotes in situ endochondral defect regeneration of the entire humeral head while simultaneously providing immediate mechanical support. In a rabbit model of total humerus resection, the designed “living prosthesis” achieved weight, macroscopic and microscopic morphologies that were comparable to those of undamaged native joints at 2 months post-implantation, with organized osteochondral tissues were regenerated both around and within the prosthesis. Notably, the “living prosthesis” displayed significantly higher osteo-integration than the blank metal prosthesis did, as evidenced by a 3-fold increase in bone ingrowth and a 2-fold increase in mechanical pull-out strength. Furthermore, the "living prosthesis" restored joint cartilage function, with rabbits exhibiting normal gait and weight-bearing capacity. The successful regeneration of fully functional humeral head tissue from a single implanted prosthesis represents technical advance in designing bioactive bone prosthesis, with promising implications for treating extreme-large osteochondral defects.
{"title":"Living joint prosthesis with in-situ tissue engineering for real-time and long-term osteoarticular reconstruction","authors":"Wei Sun , Hongwei Wu , Yiyang Yan , Xianzhu Zhang , Xudong Yao , Rui Li , Jingyi Zuo , Wenyue Li , Hongwei Ouyang","doi":"10.1016/j.bioactmat.2025.01.036","DOIUrl":"10.1016/j.bioactmat.2025.01.036","url":null,"abstract":"<div><div>The reconstruction of large osteoarticular defects caused by tumor resection or severe trauma remains a clinical challenge. Current metal prostheses exhibit a lack of osteo-chondrogenic functionality and demonstrate poor integration with host tissues. This often results in complications such as abnormal bone absorption and prosthetic loosening, which may necessitate secondary revisions. Here, we propose a paradigm-shifting “living prosthesis” strategy that combines a customized 3D-printed hollow titanium humeral prosthesis with engineered bone marrow condensations presenting bone morphogenetic protein-2 (BMP-2) and transforming growth factor–β3 (TGF-β3) from encapsulated silk fibroin hydrogels. This innovative approach promotes <em>in situ</em> endochondral defect regeneration of the entire humeral head while simultaneously providing immediate mechanical support. In a rabbit model of total humerus resection, the designed “living prosthesis” achieved weight, macroscopic and microscopic morphologies that were comparable to those of undamaged native joints at 2 months post-implantation, with organized osteochondral tissues were regenerated both around and within the prosthesis. Notably, the “living prosthesis” displayed significantly higher osteo-integration than the blank metal prosthesis did, as evidenced by a 3-fold increase in bone ingrowth and a 2-fold increase in mechanical pull-out strength. Furthermore, the \"living prosthesis\" restored joint cartilage function, with rabbits exhibiting normal gait and weight-bearing capacity. The successful regeneration of fully functional humeral head tissue from a single implanted prosthesis represents technical advance in designing bioactive bone prosthesis, with promising implications for treating extreme-large osteochondral defects.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 431-442"},"PeriodicalIF":18.0,"publicationDate":"2025-02-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143487047","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 : 2025-02-24DOI: 10.1016/j.bioactmat.2025.02.009
Lucia G. Brunel , Betty Cai , Sarah M. Hull , Uiyoung Han , Thitima Wungcharoen , Gabriella Maria Fernandes-Cunha , Youngyoon Amy Seo , Patrik K. Johansson , Sarah C. Heilshorn , David Myung
The scarcity of human donor corneal graft tissue worldwide available for corneal transplantation necessitates the development of alternative therapeutic strategies for treating patients with corneal blindness. Corneal stromal stem cells (CSSCs) have the potential to address this global shortage by allowing a single donor cornea to treat multiple patients. To directly deliver CSSCs to corneal defects within an engineered biomatrix, we developed a UNIversal Orthogonal Network (UNION) collagen bioink that crosslinks in situ with a bioorthogonal, covalent chemistry. This cell-gel therapy is optically transparent, stable against contraction forces exerted by CSSCs, and permissive to the efficient growth of corneal epithelial cells. Furthermore, CSSCs remain viable within the UNION collagen gel precursor solution under standard storage and transportation conditions. This approach promoted corneal transparency and re-epithelialization in a rabbit anterior lamellar keratoplasty model, indicating that the UNION collagen bioink serves effectively as an in situ-forming, suture-free therapy for delivering CSSCs to corneal wounds.
{"title":"In situ UNIversal Orthogonal Network (UNION) bioink deposition for direct delivery of corneal stromal stem cells to corneal wounds","authors":"Lucia G. Brunel , Betty Cai , Sarah M. Hull , Uiyoung Han , Thitima Wungcharoen , Gabriella Maria Fernandes-Cunha , Youngyoon Amy Seo , Patrik K. Johansson , Sarah C. Heilshorn , David Myung","doi":"10.1016/j.bioactmat.2025.02.009","DOIUrl":"10.1016/j.bioactmat.2025.02.009","url":null,"abstract":"<div><div>The scarcity of human donor corneal graft tissue worldwide available for corneal transplantation necessitates the development of alternative therapeutic strategies for treating patients with corneal blindness. Corneal stromal stem cells (CSSCs) have the potential to address this global shortage by allowing a single donor cornea to treat multiple patients. To directly deliver CSSCs to corneal defects within an engineered biomatrix, we developed a UNIversal Orthogonal Network (UNION) collagen bioink that crosslinks <em>in situ</em> with a bioorthogonal, covalent chemistry. This cell-gel therapy is optically transparent, stable against contraction forces exerted by CSSCs, and permissive to the efficient growth of corneal epithelial cells. Furthermore, CSSCs remain viable within the UNION collagen gel precursor solution under standard storage and transportation conditions. This approach promoted corneal transparency and re-epithelialization in a rabbit anterior lamellar keratoplasty model, indicating that the UNION collagen bioink serves effectively as an <em>in situ</em>-forming, suture-free therapy for delivering CSSCs to corneal wounds.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 414-430"},"PeriodicalIF":18.0,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474597","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 : 2025-02-22DOI: 10.1016/j.bioactmat.2025.01.033
Zhe Wang , Duo Ma , Juan Liu , Shi Xu , Fang Qiu , Liqiu Hu , Yueming Liu , Changneng Ke , Changshun Ruan
4D printing polymeric biomaterials can change their morphology or performance in response to stimuli from the external environment, compensating for the shortcomings of traditional 3D-printed static structures. This paper provides a systematic overview of 4D printing polymeric biomaterials for tissue regeneration and provides an in-depth discussion of the principles of these materials, including various smart properties, unique deformation mechanisms under stimulation conditions, and so on. A series of typical polymeric biomaterials and their composites are introduced from structural design and preparation methods, and their applications in tissue regeneration are discussed. Finally, the development prospect of 4D printing polymeric biomaterials is envisioned, aiming to provide innovative ideas and new perspectives for their more efficient and convenient application in tissue regeneration.
{"title":"4D printing polymeric biomaterials for adaptive tissue regeneration","authors":"Zhe Wang , Duo Ma , Juan Liu , Shi Xu , Fang Qiu , Liqiu Hu , Yueming Liu , Changneng Ke , Changshun Ruan","doi":"10.1016/j.bioactmat.2025.01.033","DOIUrl":"10.1016/j.bioactmat.2025.01.033","url":null,"abstract":"<div><div>4D printing polymeric biomaterials can change their morphology or performance in response to stimuli from the external environment, compensating for the shortcomings of traditional 3D-printed static structures. This paper provides a systematic overview of 4D printing polymeric biomaterials for tissue regeneration and provides an in-depth discussion of the principles of these materials, including various smart properties, unique deformation mechanisms under stimulation conditions, and so on. A series of typical polymeric biomaterials and their composites are introduced from structural design and preparation methods, and their applications in tissue regeneration are discussed. Finally, the development prospect of 4D printing polymeric biomaterials is envisioned, aiming to provide innovative ideas and new perspectives for their more efficient and convenient application in tissue regeneration.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 370-399"},"PeriodicalIF":18.0,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143471253","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 : 2025-02-22DOI: 10.1016/j.bioactmat.2025.02.013
Se-Hwan Lee , Zizhao Li , Ellen Y. Zhang , Dong Hwa Kim , Ziqi Huang , Yuna Heo , Sang Jin Lee , Hyun-Wook Kang , Jason A. Burdick , Robert L. Mauck , Su Chin Heo
Meniscus injuries present significant therapeutic challenges due to their limited self-healing capacity and the diverse biological and mechanical properties across the tissue. Conventional repair strategies do not replicate the complex zonal characteristics within the meniscus, resulting in suboptimal outcomes. In this study, we introduce an innovative fetal/adult and stiffness-tunable meniscus decellularized extracellular matrix (DEM)-based hydrogel system designed for precision repair of heterogeneous, zonal-dependent meniscus injuries. By synthesizing fetal and adult DEM hydrogels, we identified distinct cellular responses, including that hydrogels with adult meniscus-derived DEM promote more fibrochondrogenic phenotypes. The incorporation of methacrylated hyaluronic acid (MeHA) further refined the mechanical properties and injectability of the DEM-based hydrogels. The combination of fetal and adult DEM with MeHA allowed for precise tuning of stiffness, influencing cell differentiation and closely mimicking native tissue environments. In vivo tests confirmed the biocompatibility of hydrogels and their integration with native meniscus tissues. Furthermore, advanced 3D bioprinting techniques enabled the fabrication of hybrid hydrogels with biomaterial and mechanical gradients, effectively emulating the zonal properties of meniscus tissue and enhancing cell integration. This study represents a significant advance in meniscus tissue engineering, providing a promising platform for customized regenerative therapies across a range of heterogeneous fibrous connective tissues.
{"title":"Precision repair of zone-specific meniscal injuries using a tunable extracellular matrix-based hydrogel system","authors":"Se-Hwan Lee , Zizhao Li , Ellen Y. Zhang , Dong Hwa Kim , Ziqi Huang , Yuna Heo , Sang Jin Lee , Hyun-Wook Kang , Jason A. Burdick , Robert L. Mauck , Su Chin Heo","doi":"10.1016/j.bioactmat.2025.02.013","DOIUrl":"10.1016/j.bioactmat.2025.02.013","url":null,"abstract":"<div><div>Meniscus injuries present significant therapeutic challenges due to their limited self-healing capacity and the diverse biological and mechanical properties across the tissue. Conventional repair strategies do not replicate the complex zonal characteristics within the meniscus, resulting in suboptimal outcomes. In this study, we introduce an innovative fetal/adult and stiffness-tunable meniscus decellularized extracellular matrix (DEM)-based hydrogel system designed for precision repair of heterogeneous, zonal-dependent meniscus injuries. By synthesizing fetal and adult DEM hydrogels, we identified distinct cellular responses, including that hydrogels with adult meniscus-derived DEM promote more fibrochondrogenic phenotypes. The incorporation of methacrylated hyaluronic acid (MeHA) further refined the mechanical properties and injectability of the DEM-based hydrogels. The combination of fetal and adult DEM with MeHA allowed for precise tuning of stiffness, influencing cell differentiation and closely mimicking native tissue environments. <em>In vivo</em> tests confirmed the biocompatibility of hydrogels and their integration with native meniscus tissues. Furthermore, advanced 3D bioprinting techniques enabled the fabrication of hybrid hydrogels with biomaterial and mechanical gradients, effectively emulating the zonal properties of meniscus tissue and enhancing cell integration. This study represents a significant advance in meniscus tissue engineering, providing a promising platform for customized regenerative therapies across a range of heterogeneous fibrous connective tissues.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 400-413"},"PeriodicalIF":18.0,"publicationDate":"2025-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464758","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}
Senescent-endothelial cells significantly accelerate atherosclerosis progression, making the mitigation of cellular aging a promising strategy for treating the disease. Nitric oxide (NO), a low molecular weight and lipophilic gas, has been shown to penetrate cell membranes effectively and delay cell senescence. In this study, we designed and engineered osteopontin (OPN)-modified nanoliposomes (CZALO) that encapsulate L-arginine (L-Arg) and cerium-zirconium oxide nanoparticles (CZ NPs), which exhibit enzyme-like activities for targeted atherosclerosis treatment. Following inflammatory chemotaxis and OPN-mediated internalization by macrophages, CZ NPs released from CZALO nanoliposomes significantly scavenge reactive oxygen species, thereby inhibiting cholesterol uptake and promoting macrophage phenotypic transformation, resulting in both antioxidant and anti-inflammatory effects. Additionally, nitric oxide synthase (NOS) overexpressed in macrophages catalyzes L-Arg to produce NO, which is then selectively released in situ and diffuses into endothelial cells, exerting anti-aging effects by regulating senescence-associated secretory phenotype factor secretion, enhancing lysosomal function, alleviating cell cycle arrest, and reducing DNA damage. The antioxidant and anti-aging effects of CZALO nanoliposomes collectively alleviate atherosclerotic burden with minimal toxicity both in vitro and in vivo. This “two-birds-one-stone” nanotherapeutic offers a novel approach for regulating vascular microenvironment homeostasis and improving therapeutic efficiency in atherosclerosis treatment.
{"title":"Macrophage-targeting Antisenescence nanomedicine enables in-Situ NO induction for Gaseous and antioxidative atherosclerosis intervention","authors":"Yuanyuan Peng , Wei Feng , Hui Huang , Yu Chen , Shaoling Yang","doi":"10.1016/j.bioactmat.2025.02.025","DOIUrl":"10.1016/j.bioactmat.2025.02.025","url":null,"abstract":"<div><div>Senescent-endothelial cells significantly accelerate atherosclerosis progression, making the mitigation of cellular aging a promising strategy for treating the disease. Nitric oxide (NO), a low molecular weight and lipophilic gas, has been shown to penetrate cell membranes effectively and delay cell senescence. In this study, we designed and engineered osteopontin (OPN)-modified nanoliposomes (CZALO) that encapsulate L-arginine (L-Arg) and cerium-zirconium oxide nanoparticles (CZ NPs), which exhibit enzyme-like activities for targeted atherosclerosis treatment. Following inflammatory chemotaxis and OPN-mediated internalization by macrophages, CZ NPs released from CZALO nanoliposomes significantly scavenge reactive oxygen species, thereby inhibiting cholesterol uptake and promoting macrophage phenotypic transformation, resulting in both antioxidant and anti-inflammatory effects. Additionally, nitric oxide synthase (NOS) overexpressed in macrophages catalyzes L-Arg to produce NO, which is then selectively released in situ and diffuses into endothelial cells, exerting anti-aging effects by regulating senescence-associated secretory phenotype factor secretion, enhancing lysosomal function, alleviating cell cycle arrest, and reducing DNA damage. The antioxidant and anti-aging effects of CZALO nanoliposomes collectively alleviate atherosclerotic burden with minimal toxicity both <em>in vitro</em> and <em>in vivo</em>. This “two-birds-one-stone” nanotherapeutic offers a novel approach for regulating vascular microenvironment homeostasis and improving therapeutic efficiency in atherosclerosis treatment.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 294-312"},"PeriodicalIF":18.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444603","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 : 2025-02-20DOI: 10.1016/j.bioactmat.2025.02.016
Hao Li , Yongkang Yang , Tianze Gao , Runmeng Li , Chao Wang , Xue Wang , Tianyuan Zhao , Qinyu Tian , Zhixing Zhang , Ruiyang Zhang , Quanyi Guo , Zhiguo Yuan , Peifu Tang
Meniscal injury presents a formidable challenge and often leads to functional impairment and osteoarthritic progression. Meniscus tissue engineering (MTE) is a promising solution, as conventional strategies for modulating local immune responses and generating a conducive microenvironment for effective tissue repair are lacking. Recently, magnesium-containing bioactive glass nanospheres (Mg-BGNs) have shown promise in tissue regeneration. However, few studies have explored the ability of Mg-BGNs to promote meniscal regeneration. First, we verified the anti-inflammatory and fibrochondrogenic abilities of Mg-BGNs in vitro. A comprehensive in vivo evaluation of a rabbit critical-size meniscectomy model revealed that Mg-BGNs have multiple effects on meniscal reconstruction and effectively promote fibrochondrogenesis, collagen deposition, and cartilage protection. Multiomics analysis was subsequently performed to further explore the mechanism by which Mg-BGNs regulate the regenerative microenvironment. Mechanistically, Mg-BGNs first activate the TRPM7 ion channel through the PI3K/AKT signaling pathway to promote the cellular function of synovium-derived mesenchymal stem cells and then activate the PPARγ/NF-κB axis to modulate macrophage polarization and inflammatory reactions. We demonstrated that Mg2+ is critical for the crosstalk among biomaterials, immune cells, and effector cells in Mg-BGN-mediated tissue regeneration. This study provides a theoretical basis for the application of Mg-BGNs as nanomedicines to achieve in situ tissue regeneration in complex intrajoint pathological microenvironments.
{"title":"3D-printed PCL scaffolds combined with injectable sodium alginate/magnesium-doped mesoporous bioactive glass nanosphere hydrogel for meniscus regeneration: In vitro, In vivo, and multiomics-based therapeutic analyses","authors":"Hao Li , Yongkang Yang , Tianze Gao , Runmeng Li , Chao Wang , Xue Wang , Tianyuan Zhao , Qinyu Tian , Zhixing Zhang , Ruiyang Zhang , Quanyi Guo , Zhiguo Yuan , Peifu Tang","doi":"10.1016/j.bioactmat.2025.02.016","DOIUrl":"10.1016/j.bioactmat.2025.02.016","url":null,"abstract":"<div><div>Meniscal injury presents a formidable challenge and often leads to functional impairment and osteoarthritic progression. Meniscus tissue engineering (MTE) is a promising solution, as conventional strategies for modulating local immune responses and generating a conducive microenvironment for effective tissue repair are lacking. Recently, magnesium-containing bioactive glass nanospheres (Mg-BGNs) have shown promise in tissue regeneration. However, few studies have explored the ability of Mg-BGNs to promote meniscal regeneration. First, we verified the anti-inflammatory and fibrochondrogenic abilities of Mg-BGNs in vitro. A comprehensive in vivo evaluation of a rabbit critical-size meniscectomy model revealed that Mg-BGNs have multiple effects on meniscal reconstruction and effectively promote fibrochondrogenesis, collagen deposition, and cartilage protection. Multiomics analysis was subsequently performed to further explore the mechanism by which Mg-BGNs regulate the regenerative microenvironment. Mechanistically, Mg-BGNs first activate the TRPM7 ion channel through the PI3K/AKT signaling pathway to promote the cellular function of synovium-derived mesenchymal stem cells and then activate the PPARγ/NF-κB axis to modulate macrophage polarization and inflammatory reactions. We demonstrated that Mg<sup>2+</sup> is critical for the crosstalk among biomaterials, immune cells, and effector cells in Mg-BGN-mediated tissue regeneration. This study provides a theoretical basis for the application of Mg-BGNs as nanomedicines to achieve in situ tissue regeneration in complex intrajoint pathological microenvironments.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 313-335"},"PeriodicalIF":18.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444604","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 : 2025-02-20DOI: 10.1016/j.bioactmat.2025.02.023
Mohamed Amhmed , Brandon Kieft , Abdullah Almegbel , Lari Häkkinen , Markus Haapasalo , He Liu , Ya Shen
The persistence of bacteria in the root canal system is the primary cause of recurrent apical periodontitis. The adaptability of residual bacteria to changing environmental conditions is a key survival strategy of biofilms, often leading to endodontic treatment failure. DJK-5 is a protease-resistant, broad-spectrum D-enantiomeric peptide that degrades or prevents the accumulation of guanosine penta- and tetraphosphates, which are important for biofilm formation. We evaluated the effects of primary antimicrobial agents and nutrient conditions on the recovery, metabolism, diversity, and composition of oral biofilms, and investigated how these factors affect the efficacy of DJK-5 and chlorhexidine (CHX) during re-exposure. Primary irrigants and nutrient conditions significantly influenced biofilm recovery, metabolic activity, diversity, and composition. Biofilm recovery was slower in nutrient-poor groups compared to nutrient-rich ones, and nutrient availability had the greatest effect on shaping both the diversity and composition of the biofilms. Water and DJK-5 groups showed similar biofilm diversity trends, while CHX generally led to lower diversity. Results indicate that primary irrigants and nutrient conditions significantly impact biofilm composition, diversity, and recovery. However, these changes did not compromise DJK-5's effectiveness in killing of biofilm microbes during re-exposure of recovered biofilms.
{"title":"Primary and Re-exposure effects of D-enantiomeric peptide on metabolism, diversity, and composition of oral biofilms at different stages of recovery","authors":"Mohamed Amhmed , Brandon Kieft , Abdullah Almegbel , Lari Häkkinen , Markus Haapasalo , He Liu , Ya Shen","doi":"10.1016/j.bioactmat.2025.02.023","DOIUrl":"10.1016/j.bioactmat.2025.02.023","url":null,"abstract":"<div><div>The persistence of bacteria in the root canal system is the primary cause of recurrent apical periodontitis. The adaptability of residual bacteria to changing environmental conditions is a key survival strategy of biofilms, often leading to endodontic treatment failure. DJK-5 is a protease-resistant, broad-spectrum D-enantiomeric peptide that degrades or prevents the accumulation of guanosine penta- and tetraphosphates, which are important for biofilm formation. We evaluated the effects of primary antimicrobial agents and nutrient conditions on the recovery, metabolism, diversity, and composition of oral biofilms, and investigated how these factors affect the efficacy of DJK-5 and chlorhexidine (CHX) during re-exposure. Primary irrigants and nutrient conditions significantly influenced biofilm recovery, metabolic activity, diversity, and composition. Biofilm recovery was slower in nutrient-poor groups compared to nutrient-rich ones, and nutrient availability had the greatest effect on shaping both the diversity and composition of the biofilms. Water and DJK-5 groups showed similar biofilm diversity trends, while CHX generally led to lower diversity. Results indicate that primary irrigants and nutrient conditions significantly impact biofilm composition, diversity, and recovery. However, these changes did not compromise DJK-5's effectiveness in killing of biofilm microbes during re-exposure of recovered biofilms.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 257-272"},"PeriodicalIF":18.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444600","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 : 2025-02-20DOI: 10.1016/j.bioactmat.2025.02.003
Keerthi Subramanian Iyer , Lei Bao , Jiali Zhai , Aparna Jayachandran , Rodney Luwor , Jiao Jiao Li , Haiyan Li
Extrusion-based 3D bioprinting is being increasingly adopted as a versatile biofabrication method for making biomimetic constructs in tissue engineering. However, the lack of ideal bioinks continues to limit its broader application. Conventional hydrogel-based bioinks typically possess a densely crosslinked nanoporous structure that hinders their ability to fully support cell behavior. Microgel-based bioinks have recently emerged as a promising alternative due to their enhanced printability and functionality. This review will begin with the evolution of the “bioink" concept, followed by a discussion on bioink categories and the requirements of ideal bioinks. It will then introduce hydrogel-based bioinks and their limitations, followed by a definition of microgels and microgel-based bioinks and a discussion of their key properties, highlighting their differences compared to conventional hydrogel-based bioinks. Topics on microgel-based bioinks are then presented in order of the printing process: pre-printing (fabrication of microgels and formulation of microgel-based bioinks), during printing and post-printing (microgel assembly kinetics). Uniquely, this review will examine the various applications of microgel-based bioinks in tissue engineering, summarizing their advantages and limitations. Finally, the current challenges and future perspectives of using microgel-based bioinks are discussed. This review comprehensively examines microgel-based bioinks for 3D bioprinting, highlighting their potential to overcome current challenges and setting the stage for their future applications in creating complex, functional tissue engineering scaffolds.
{"title":"Microgel-based bioink for extrusion-based 3D bioprinting and its applications in tissue engineering","authors":"Keerthi Subramanian Iyer , Lei Bao , Jiali Zhai , Aparna Jayachandran , Rodney Luwor , Jiao Jiao Li , Haiyan Li","doi":"10.1016/j.bioactmat.2025.02.003","DOIUrl":"10.1016/j.bioactmat.2025.02.003","url":null,"abstract":"<div><div>Extrusion-based 3D bioprinting is being increasingly adopted as a versatile biofabrication method for making biomimetic constructs in tissue engineering. However, the lack of ideal bioinks continues to limit its broader application. Conventional hydrogel-based bioinks typically possess a densely crosslinked nanoporous structure that hinders their ability to fully support cell behavior. Microgel-based bioinks have recently emerged as a promising alternative due to their enhanced printability and functionality. This review will begin with the evolution of the “bioink\" concept, followed by a discussion on bioink categories and the requirements of ideal bioinks. It will then introduce hydrogel-based bioinks and their limitations, followed by a definition of microgels and microgel-based bioinks and a discussion of their key properties, highlighting their differences compared to conventional hydrogel-based bioinks. Topics on microgel-based bioinks are then presented in order of the printing process: pre-printing (fabrication of microgels and formulation of microgel-based bioinks), during printing and post-printing (microgel assembly kinetics). Uniquely, this review will examine the various applications of microgel-based bioinks in tissue engineering, summarizing their advantages and limitations. Finally, the current challenges and future perspectives of using microgel-based bioinks are discussed. This review comprehensively examines microgel-based bioinks for 3D bioprinting, highlighting their potential to overcome current challenges and setting the stage for their future applications in creating complex, functional tissue engineering scaffolds.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 273-293"},"PeriodicalIF":18.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143444602","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 : 2025-02-20DOI: 10.1016/j.bioactmat.2025.02.021
Wenbin Cai , Fanlei Yang , Chao Yang , Yu Liu , Hao Xu , Wen Zhang , Bin Li , Fengxuan Han , Zongping Luo , Ting Liang
Nucleus pulposus (NP) tissue engineering brings new hope in the repair of intervertebral disc degeneration (IVDD). IVDD is often accompanied by multiscale changes in the mechanical microenvironment, including the changes of mechanical property of collagen fibril, NP tissue, and mechanical instability of spine. In this study, a multiscale mechanically-adapted strategy is proposed to promote NP repair. To achieve this goal, a viscoelastic-adapted dual-network hydrogel (PVA-DN) is constructed. The hydrogel with multiscale tunable viscoelasticity and dynamic compression condition is used to meet the multiscale mechanical requirements of NP regeneration. The results show that the viscoelastic hydrogel promotes the proliferation, migration and adhesion of nucleus pulposus cell (NPC) as well as the secretion of NP-specific extracellular matrix. RNA-seq results show that it attenuates the inflammatory microenvironment by inhibiting the IL-17 signaling pathway. Appropriate dynamic compression applied to the viscoelastic scaffold further promotes the physiological function of NPC, and the viscoelasticity of hydrogel protects against NPC damage induced by excessive compression. Animal experiments demonstrate that the viscoelastic hydrogel effectively restores disc mechanical function and delays disc degeneration in rats. Findings from this study highlight that the multiscale mechanically-adapted strategy is effective in the repair of IVDD.
{"title":"Multiscale mechanical-adapted hydrogels for the repair of intervertebral disc degeneration","authors":"Wenbin Cai , Fanlei Yang , Chao Yang , Yu Liu , Hao Xu , Wen Zhang , Bin Li , Fengxuan Han , Zongping Luo , Ting Liang","doi":"10.1016/j.bioactmat.2025.02.021","DOIUrl":"10.1016/j.bioactmat.2025.02.021","url":null,"abstract":"<div><div>Nucleus pulposus (NP) tissue engineering brings new hope in the repair of intervertebral disc degeneration (IVDD). IVDD is often accompanied by multiscale changes in the mechanical microenvironment, including the changes of mechanical property of collagen fibril, NP tissue, and mechanical instability of spine. In this study, a multiscale mechanically-adapted strategy is proposed to promote NP repair. To achieve this goal, a viscoelastic-adapted dual-network hydrogel (PVA-DN) is constructed. The hydrogel with multiscale tunable viscoelasticity and dynamic compression condition is used to meet the multiscale mechanical requirements of NP regeneration. The results show that the viscoelastic hydrogel promotes the proliferation, migration and adhesion of nucleus pulposus cell (NPC) as well as the secretion of NP-specific extracellular matrix. RNA-seq results show that it attenuates the inflammatory microenvironment by inhibiting the IL-17 signaling pathway. Appropriate dynamic compression applied to the viscoelastic scaffold further promotes the physiological function of NPC, and the viscoelasticity of hydrogel protects against NPC damage induced by excessive compression. Animal experiments demonstrate that the viscoelastic hydrogel effectively restores disc mechanical function and delays disc degeneration in rats. Findings from this study highlight that the multiscale mechanically-adapted strategy is effective in the repair of IVDD.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"48 ","pages":"Pages 336-352"},"PeriodicalIF":18.0,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143454909","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}
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