Pub Date : 2025-01-03DOI: 10.1016/j.bioactmat.2024.12.024
Xiang Lin , Anne M. Filppula , Yuanjin Zhao , Luoran Shang , Hongbo Zhang
Long-term exposure to ultraviolet radiation compromises skin structural integrity and results in disruption of normal physiological functions. Stem cells have gained attention in anti-photoaging, while controlling the tissue mechanical microenvironment of cell delivery sites is crucial for regulating cell fate and achieving optimal therapeutic performances. Here, we introduce a mechanically regulated human recombinant collagen (RHC) microcarrier generated through microfluidics, which is capable of modulating stem cell differentiation to treat photoaged skin. By controlling the cross-linking parameters, the mechanical properties of microcarriers could precisely tuned to optimize the stem cell differentiation. The microcarriers are surface functionalized with fibronectin (Fn)-platelet derived growth factor-BB (PDGF-BB) to facilitate adipose derived mesenchymal stem cells (Ad-MSCs) loading. In in vivo experiments, subcutaneous injection of stem cell loaded RHC microcarriers significantly reduced skin wrinkles after ultraviolet-injury, effectively promoted collagen synthesis, and increased vascular density. These encouraging results indicate that the present mechanically regulated microcarriers have great potential to deliver stem cells and regulate their differentiation for anti-photoaging treatments.
{"title":"Mechanically regulated microcarriers with stem cell loading for skin photoaging therapy","authors":"Xiang Lin , Anne M. Filppula , Yuanjin Zhao , Luoran Shang , Hongbo Zhang","doi":"10.1016/j.bioactmat.2024.12.024","DOIUrl":"10.1016/j.bioactmat.2024.12.024","url":null,"abstract":"<div><div>Long-term exposure to ultraviolet radiation compromises skin structural integrity and results in disruption of normal physiological functions. Stem cells have gained attention in anti-photoaging, while controlling the tissue mechanical microenvironment of cell delivery sites is crucial for regulating cell fate and achieving optimal therapeutic performances. Here, we introduce a mechanically regulated human recombinant collagen (RHC) microcarrier generated through microfluidics, which is capable of modulating stem cell differentiation to treat photoaged skin. By controlling the cross-linking parameters, the mechanical properties of microcarriers could precisely tuned to optimize the stem cell differentiation. The microcarriers are surface functionalized with fibronectin (Fn)-platelet derived growth factor-BB (PDGF-BB) to facilitate adipose derived mesenchymal stem cells (Ad-MSCs) loading. In <em>in vivo</em> experiments, subcutaneous injection of stem cell loaded RHC microcarriers significantly reduced skin wrinkles after ultraviolet-injury, effectively promoted collagen synthesis, and increased vascular density. These encouraging results indicate that the present mechanically regulated microcarriers have great potential to deliver stem cells and regulate their differentiation for anti-photoaging treatments.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"46 ","pages":"Pages 448-456"},"PeriodicalIF":18.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754972/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027939","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 : 2025-01-03DOI: 10.1016/j.bioactmat.2024.12.025
Yupu Liu , Yawei Du , Juan Wang , Longxi Wu, Feng Lin, Wenguo Cui
Bioelectrical stimulation is a powerful technique used to promote tissue regeneration, but it can be hindered by an “electrical overload” phenomenon in the core region of stimulation. We develop a threaded microneedle electrode system that protects against “electrical overload” by delivering medicinal hydrogel microspheres into the core regions. The threaded needle body is coated with polydopamine and chitosan to enhance the adhesion of microspheres, which are loaded into the threaded grooves, allowing for their stereoscopic release in the core regions. After the electrode is inserted, the microspheres can be delivered three-dimensionally through physical swelling and the shear-thinning effect of chitosan, mitigating the electrical damage. Microspheres are designed to release alkylated vitamin B12 and vitamin E, providing antioxidant and cell protection effects upon in-situ activation, reducing reactive oxygen species (ROS) by 72.8 % and cell death by 59.5 %. In the model of peripheral nerve injury, the electrode system improves the overall antioxidant capacity by 78.5 % and protects the surrounding cells. Additionally, it leads to an improved nerve conduction velocity ratio of 41.9 % and sciatic nerve function index of 12.1 %, indicating enhanced neuroregeneration. The threaded microneedle electrode system offers a promising approach for nerve repair by inhibiting “electrical overload”, potentially improving outcomes for tissue regeneration.
{"title":"Reduce electrical overload via threaded Chinese acupuncture in nerve electrical therapy","authors":"Yupu Liu , Yawei Du , Juan Wang , Longxi Wu, Feng Lin, Wenguo Cui","doi":"10.1016/j.bioactmat.2024.12.025","DOIUrl":"10.1016/j.bioactmat.2024.12.025","url":null,"abstract":"<div><div>Bioelectrical stimulation is a powerful technique used to promote tissue regeneration, but it can be hindered by an “electrical overload” phenomenon in the core region of stimulation. We develop a threaded microneedle electrode system that protects against “electrical overload” by delivering medicinal hydrogel microspheres into the core regions. The threaded needle body is coated with polydopamine and chitosan to enhance the adhesion of microspheres, which are loaded into the threaded grooves, allowing for their stereoscopic release in the core regions. After the electrode is inserted, the microspheres can be delivered three-dimensionally through physical swelling and the shear-thinning effect of chitosan, mitigating the electrical damage. Microspheres are designed to release alkylated vitamin B12 and vitamin E, providing antioxidant and cell protection effects upon <em>in-situ</em> activation, reducing reactive oxygen species (ROS) by 72.8 % and cell death by 59.5 %. In the model of peripheral nerve injury, the electrode system improves the overall antioxidant capacity by 78.5 % and protects the surrounding cells. Additionally, it leads to an improved nerve conduction velocity ratio of 41.9 % and sciatic nerve function index of 12.1 %, indicating enhanced neuroregeneration. The threaded microneedle electrode system offers a promising approach for nerve repair by inhibiting “electrical overload”, potentially improving outcomes for tissue regeneration.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"46 ","pages":"Pages 476-493"},"PeriodicalIF":18.0,"publicationDate":"2025-01-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754975/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027567","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}
mRNA therapeutics is revolutionizing the treatment concepts toward many diseases including cancer. The potential of mRNA is, however, frequently limited by modest control over site of transfection. Here, we have explored a library of multivalent ionizable lipid-polypeptides (MILP) to achieve robust mRNA complexation and tumor-confined transfection. Leveraging the multivalent electrostatic, hydrophobic, and H-bond interactions, MILP efficiently packs both mRNA and plasmid DNA into sub-80 nm nanoparticles that are stable against lyophilization and long-term storage. The best MILP@mRNA complexes afford 8-fold more cellular uptake than SM-102 lipid nanoparticle formulation (SM-102 LNP), efficient endosomal disruption, and high transfection in different cells. Interestingly, MILP@mLuc displays exclusive tumor residence and distribution via multivalency-directed strong affinity and transcytosis, and affords specific protein expression in tumor cells and macrophages at tumor sites following intratumoral injection, in sharp contrast to the indiscriminate distribution and transfection in main organs of SM-102 LNP. Notably, MILP@mIL-12 with specific and efficient cytokine expression generates significant remodeling of tumor immunoenvironments and remarkable antitumor response in subcutaneous Lewis lung carcinoma and 4T1 tumor xenografts. MILP provides a unique strategy to site-specific transfection that may greatly broaden the applications of mRNA.
{"title":"Multivalent ionizable lipid-polypeptides for tumor-confined mRNA transfection","authors":"Xiaofei Zhao, Yueyue Zhang, Xin Wang, Ziming Fu, Zhiyuan Zhong, Chao Deng","doi":"10.1016/j.bioactmat.2024.12.032","DOIUrl":"10.1016/j.bioactmat.2024.12.032","url":null,"abstract":"<div><div>mRNA therapeutics is revolutionizing the treatment concepts toward many diseases including cancer. The potential of mRNA is, however, frequently limited by modest control over site of transfection. Here, we have explored a library of multivalent ionizable lipid-polypeptides (MILP) to achieve robust mRNA complexation and tumor-confined transfection. Leveraging the multivalent electrostatic, hydrophobic, and H-bond interactions, MILP efficiently packs both mRNA and plasmid DNA into sub-80 nm nanoparticles that are stable against lyophilization and long-term storage. The best MILP@mRNA complexes afford 8-fold more cellular uptake than SM-102 lipid nanoparticle formulation (SM-102 LNP), efficient endosomal disruption, and high transfection in different cells. Interestingly, MILP@mLuc displays exclusive tumor residence and distribution via multivalency-directed strong affinity and transcytosis, and affords specific protein expression in tumor cells and macrophages at tumor sites following intratumoral injection, in sharp contrast to the indiscriminate distribution and transfection in main organs of SM-102 LNP. Notably, MILP@mIL-12 with specific and efficient cytokine expression generates significant remodeling of tumor immunoenvironments and remarkable antitumor response in subcutaneous Lewis lung carcinoma and 4T1 tumor xenografts. MILP provides a unique strategy to site-specific transfection that may greatly broaden the applications of mRNA.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"46 ","pages":"Pages 423-433"},"PeriodicalIF":18.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027563","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 : 2025-01-02DOI: 10.1016/j.bioactmat.2024.12.014
Zhuoling Tian , Ruoheng Gu , Wenyue Xie , Xing Su , Zuoying Yuan , Zhuo Wan , Hao Wang , Yaqian Liu , Yuting Feng , Xiaozhi Liu , Jianyong Huang
Gelatin-based biomaterials have emerged as promising candidates for bioadhesives due to their biodegradability and biocompatibility. However, they often face limitations due to the uncontrollable phase transition of gelatin, which is dominated by hydrogen bonds between peptide chains. Here, we developed controllable phase transition gelatin-based (CPTG) bioadhesives by regulating the dynamic balance of hydrogen bonds between the peptide chains using 2-hydroxyethylurea (HU) and punicalagin (PA). These CPTG bioadhesives exhibited significant enhancements in adhesion energy and injectability even at 4 °C compared to traditional gelatin bioadhesives. The developed bioadhesives could achieve self-reinforcing interfacial adhesion upon contact with moist wound tissues. This effect was attributed to HU diffusion, which disrupted the dynamic balance of hydrogen bonds and therefore induced a localized structural densification. This process was further facilitated by the presence of pyrogallol from PA. Furthermore, the CPTG bioadhesive could modulate the immune microenvironment, offering antibacterial, antioxidant, and immune-adjustable properties, thereby accelerating diabetic wound healing, as confirmed in a diabetic wound rat model. This proposed design strategy is not only crucial for developing controllable phase-transition bioadhesives for diverse applications, but also paves the way for broadening the potential applications of gelatin-based biomaterials.
{"title":"Hydrogen bonding-mediated phase-transition gelatin-based bioadhesives to regulate immune microenvironment for diabetic wound healing","authors":"Zhuoling Tian , Ruoheng Gu , Wenyue Xie , Xing Su , Zuoying Yuan , Zhuo Wan , Hao Wang , Yaqian Liu , Yuting Feng , Xiaozhi Liu , Jianyong Huang","doi":"10.1016/j.bioactmat.2024.12.014","DOIUrl":"10.1016/j.bioactmat.2024.12.014","url":null,"abstract":"<div><div>Gelatin-based biomaterials have emerged as promising candidates for bioadhesives due to their biodegradability and biocompatibility. However, they often face limitations due to the uncontrollable phase transition of gelatin, which is dominated by hydrogen bonds between peptide chains. Here, we developed controllable phase transition gelatin-based (CPTG) bioadhesives by regulating the dynamic balance of hydrogen bonds between the peptide chains using 2-hydroxyethylurea (HU) and punicalagin (PA). These CPTG bioadhesives exhibited significant enhancements in adhesion energy and injectability even at 4 °C compared to traditional gelatin bioadhesives. The developed bioadhesives could achieve self-reinforcing interfacial adhesion upon contact with moist wound tissues. This effect was attributed to HU diffusion, which disrupted the dynamic balance of hydrogen bonds and therefore induced a localized structural densification. This process was further facilitated by the presence of pyrogallol from PA. Furthermore, the CPTG bioadhesive could modulate the immune microenvironment, offering antibacterial, antioxidant, and immune-adjustable properties, thereby accelerating diabetic wound healing, as confirmed in a diabetic wound rat model. This proposed design strategy is not only crucial for developing controllable phase-transition bioadhesives for diverse applications, but also paves the way for broadening the potential applications of gelatin-based biomaterials.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"46 ","pages":"Pages 434-447"},"PeriodicalIF":18.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755075/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027934","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 : 2025-01-02DOI: 10.1016/j.bioactmat.2024.12.026
Alexandre Henrique dos Reis-Prado , Maedeh Rahimnejad , Renan Dal-Fabbro , Priscila Toninatto Alves de Toledo , Caroline Anselmi , Pedro Henrique Chaves de Oliveira , J. Christopher Fenno , Luciano Tavares Angelo Cintra , Francine Benetti , Marco C. Bottino
Injectable biomaterials, such as thermosensitive chitosan (CH)-based hydrogels, present a highly translational potential in dentistry due to their minimally invasive application, adaptability to irregular defects/shapes, and ability to carry therapeutic drugs. This work explores the incorporation of azithromycin (AZI) into thermosensitive CH hydrogels for use as an intracanal medication in regenerative endodontic procedures (REPs). The morphological and chemical characteristics of the hydrogel were assessed by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and Fourier transform infrared spectroscopy (FTIR). The thermosensitivity, gelation kinetics, compressive strength, cytocompatibility, and antibacterial efficacy were evaluated according to well-established protocols. An in vivo model of periapical disease and evoked bleeding in rats' immature permanent teeth was performed to determine disinfection, tissue repair, and root formation. AZI was successfully incorporated into interconnected porous CH hydrogels, which retained their thermosensitivity. The mechanical and rheological findings indicated that adding AZI did not adversely affect the hydrogels’ strength and injectability. Incorporating 3 % and 5 % AZI into the hydrogels led to minimal cytotoxic effects compared to higher concentrations while enhancing the antibacterial response against endodontic bacteria. AZI-laden hydrogel significantly decreased E. faecalis biofilm compared to the controls. Regarding tissue response, the 3 % AZI-laden hydrogel improved mineralized tissue formation and vascularization compared to untreated teeth and those treated with double antibiotic paste. Our findings demonstrate that adding 3 % AZI into CH hydrogels ablates infection and supports neotissue formation in vivo when applied to a clinically relevant model of regenerative endodontics.
{"title":"Injectable thermosensitive antibiotic-laden chitosan hydrogel for regenerative endodontics","authors":"Alexandre Henrique dos Reis-Prado , Maedeh Rahimnejad , Renan Dal-Fabbro , Priscila Toninatto Alves de Toledo , Caroline Anselmi , Pedro Henrique Chaves de Oliveira , J. Christopher Fenno , Luciano Tavares Angelo Cintra , Francine Benetti , Marco C. Bottino","doi":"10.1016/j.bioactmat.2024.12.026","DOIUrl":"10.1016/j.bioactmat.2024.12.026","url":null,"abstract":"<div><div>Injectable biomaterials, such as thermosensitive chitosan (CH)-based hydrogels, present a highly translational potential in dentistry due to their minimally invasive application, adaptability to irregular defects/shapes, and ability to carry therapeutic drugs. This work explores the incorporation of azithromycin (AZI) into thermosensitive CH hydrogels for use as an intracanal medication in regenerative endodontic procedures (REPs). The morphological and chemical characteristics of the hydrogel were assessed by scanning electron microscopy (SEM), energy dispersive spectroscopy (EDS), and Fourier transform infrared spectroscopy (FTIR). The thermosensitivity, gelation kinetics, compressive strength, cytocompatibility, and antibacterial efficacy were evaluated according to well-established protocols. An <em>in vivo</em> model of periapical disease and evoked bleeding in rats' immature permanent teeth was performed to determine disinfection, tissue repair, and root formation. AZI was successfully incorporated into interconnected porous CH hydrogels, which retained their thermosensitivity. The mechanical and rheological findings indicated that adding AZI did not adversely affect the hydrogels’ strength and injectability. Incorporating 3 % and 5 % AZI into the hydrogels led to minimal cytotoxic effects compared to higher concentrations while enhancing the antibacterial response against endodontic bacteria. AZI-laden hydrogel significantly decreased <em>E. faecalis</em> biofilm compared to the controls. Regarding tissue response, the 3 % AZI-laden hydrogel improved mineralized tissue formation and vascularization compared to untreated teeth and those treated with double antibiotic paste. Our findings demonstrate that adding 3 % AZI into CH hydrogels ablates infection and supports neotissue formation <em>in vivo</em> when applied to a clinically relevant model of regenerative endodontics.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"46 ","pages":"Pages 406-422"},"PeriodicalIF":18.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11754974/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027937","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 : 2025-01-02DOI: 10.1016/j.bioactmat.2024.12.017
Jiao Mu , Xiang Zou , Xinjie Bao , Zhaoyang Yang , Peng Hao , Hongmei Duan , Wen Zhao , Yudan Gao , Jinting Wu , Kun Miao , Kwok-Fai So , Liang Chen , Ying Mao , Xiaoguang Li
The mammalian brain has an extremely limited ability to regenerate lost neurons and to recover function following ischemic stroke. A biomaterial strategy of slowly-releasing various regeneration-promoting factors to activate endogenous neurogenesis represents a safe and practical neuronal replacement therapy. In this study, basic fibroblast growth factor (bFGF)-Chitosan gel is injected into the stroke cavity. This approach promotes the proliferation of vascular endothelial cell, the formation of functional vascular network, and the final restoration of cerebral blood flow. Additionally, bFGF-Chitosan gel activates neural progenitor cells (NPCs) in the subventricular zone (SVZ), promotes the NPCs’ migration toward the stroke cavity and differentiation into mature neurons with diverse cell types (inhibitory gamma-aminobutyric acid neurons and excitatory glutamatergic neuron) and layer architecture (superficial cortex and deep cortex). These new-born neurons form functional synaptic connections with the host brain and reconstruct nascent neural networks. Furthermore, synaptogenesis in the stroke cavity and Nestin lineage cells respectively contribute to the improvement of sensorimotor function induced by bFGF-Chitosan gel after ischemic stroke. Lastly, bFGF-Chitosan gel inhibits microglia activation in the peri-infarct cortex. Our findings indicate that filling the stroke cavity with bFGF-Chitosan “brain glue” promotes angiogenesis, endogenous neurogenesis and synaptogenesis to restore function, offering innovative ideas and methods for the clinical treatment of ischemic stroke.
{"title":"bFGF-Chitosan “brain glue” promotes functional recovery after cortical ischemic stroke","authors":"Jiao Mu , Xiang Zou , Xinjie Bao , Zhaoyang Yang , Peng Hao , Hongmei Duan , Wen Zhao , Yudan Gao , Jinting Wu , Kun Miao , Kwok-Fai So , Liang Chen , Ying Mao , Xiaoguang Li","doi":"10.1016/j.bioactmat.2024.12.017","DOIUrl":"10.1016/j.bioactmat.2024.12.017","url":null,"abstract":"<div><div>The mammalian brain has an extremely limited ability to regenerate lost neurons and to recover function following ischemic stroke. A biomaterial strategy of slowly-releasing various regeneration-promoting factors to activate endogenous neurogenesis represents a safe and practical neuronal replacement therapy. In this study, basic fibroblast growth factor (bFGF)-Chitosan gel is injected into the stroke cavity. This approach promotes the proliferation of vascular endothelial cell, the formation of functional vascular network, and the final restoration of cerebral blood flow. Additionally, bFGF-Chitosan gel activates neural progenitor cells (NPCs) in the subventricular zone (SVZ), promotes the NPCs’ migration toward the stroke cavity and differentiation into mature neurons with diverse cell types (inhibitory gamma-aminobutyric acid neurons and excitatory glutamatergic neuron) and layer architecture (superficial cortex and deep cortex). These new-born neurons form functional synaptic connections with the host brain and reconstruct nascent neural networks. Furthermore, synaptogenesis in the stroke cavity and Nestin lineage cells respectively contribute to the improvement of sensorimotor function induced by bFGF-Chitosan gel after ischemic stroke. Lastly, bFGF-Chitosan gel inhibits microglia activation in the peri-infarct cortex. Our findings indicate that filling the stroke cavity with bFGF-Chitosan “brain glue” promotes angiogenesis, endogenous neurogenesis and synaptogenesis to restore function, offering innovative ideas and methods for the clinical treatment of ischemic stroke.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"46 ","pages":"Pages 386-405"},"PeriodicalIF":18.0,"publicationDate":"2025-01-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11755050/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143027929","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 : 2024-12-31DOI: 10.1016/j.bioactmat.2024.12.021
Prayas Chakma Shanto , Seongsu Park , Md Abdullah Al Fahad , Myeongki Park , Byong-Taek Lee
Articular cartilage has a limited self-healing capacity, leading to joint degeneration and osteoarthritis over time. Therefore, bioactive scaffolds are gaining attention as a promising approach to regenerating and repairing damaged articular cartilage through tissue engineering. In this study, we reported on a novel 3D bio-printed proteinaceous bioactive scaffolds combined with natural porcine cancellous bone dECM, tempo-oxidized cellulose nanofiber (TOCN), and alginate carriers for TGF-β1, FGF-18, and ADSCs to repair cartilage defects. The characterization results demonstrate that the 3D scaffolds are physically stable and facilitate a controlled dual release of TGF-β1 and FGF-18. Moreover, the key biological proteins within the bioactive scaffold actively interact with the biological systems to create a favorable microenvironment for cartilage regeneration. Importantly, the in vitro, in vivo, and in silico simulation showed that the scaffolds promote stem cell recruitment, migration, proliferation, and ECM deposition, and synergistic effects of TGF-β1/FGF-18 with the bioactive scaffolds significantly regulate stem cell chondrogenesis by activating the PI3K/AKT and TGFβ1/Smad4 signaling pathways. After implantation, the proteinaceous bioactive scaffold led to the regeneration of mechanically robust, full-thickness cartilage tissue that closely resembles native cartilage. Thus, these findings may provide a promising approach for regulating stem cell chondrogenesis and treating in situ cartilage regeneration.
{"title":"3D bio-printed proteinaceous bioactive scaffold loaded with dual growth factor enhanced chondrogenesis and in situ cartilage regeneration","authors":"Prayas Chakma Shanto , Seongsu Park , Md Abdullah Al Fahad , Myeongki Park , Byong-Taek Lee","doi":"10.1016/j.bioactmat.2024.12.021","DOIUrl":"10.1016/j.bioactmat.2024.12.021","url":null,"abstract":"<div><div>Articular cartilage has a limited self-healing capacity, leading to joint degeneration and osteoarthritis over time. Therefore, bioactive scaffolds are gaining attention as a promising approach to regenerating and repairing damaged articular cartilage through tissue engineering. In this study, we reported on a novel 3D bio-printed proteinaceous bioactive scaffolds combined with natural porcine cancellous bone dECM, tempo-oxidized cellulose nanofiber (TOCN), and alginate carriers for TGF-β1, FGF-18, and ADSCs to repair cartilage defects. The characterization results demonstrate that the 3D scaffolds are physically stable and facilitate a controlled dual release of TGF-β1 and FGF-18. Moreover, the key biological proteins within the bioactive scaffold actively interact with the biological systems to create a favorable microenvironment for cartilage regeneration. Importantly, the <em>in vitro</em>, <em>in vivo</em>, and in silico simulation showed that the scaffolds promote stem cell recruitment, migration, proliferation, and ECM deposition, and synergistic effects of TGF-β1/FGF-18 with the bioactive scaffolds significantly regulate stem cell chondrogenesis by activating the PI3K/AKT and TGFβ1/Smad4 signaling pathways. After implantation, the proteinaceous bioactive scaffold led to the regeneration of mechanically robust, full-thickness cartilage tissue that closely resembles native cartilage. Thus, these findings may provide a promising approach for regulating stem cell chondrogenesis and treating in situ cartilage regeneration.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"46 ","pages":"Pages 365-385"},"PeriodicalIF":18.0,"publicationDate":"2024-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11751550/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143021965","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 : 2024-12-27DOI: 10.1016/j.bioactmat.2024.12.023
Kishwor Poudel , Zhenyu Ji , Ching-Ni Njauw , Anpuchchelvi Rajadurai , Brijesh Bhayana , Ryan J. Sullivan , Jong Oh Kim , Hensin Tsao
Cancer nanovaccines hold the promise for personalization, precision, and pliability by integrating all the elements essential for effective immune stimulation. An effective immune response requires communication and interplay between antigen-presenting cells (APCs), tumor cells, and immune cells to stimulate, extend, and differentiate antigen-specific and non-specific anti-tumor immune cells. The versatility of nanomedicine can be adapted to deliver both immunoadjuvant payloads and antigens from the key players in immunity (i.e., APCs and tumor cells). The imperative for novel cancer medicine is particularly pressing for less common but more devastating KIT-mutated acral and mucosal melanomas that are resistant to small molecule c-kit and immune checkpoint inhibitors. To overcome this challenge, we successfully engineered nanotechnology-enabled hybrid biomimetic nanovaccine (HBNV) comprised of membrane proteins (antigens to activate immunity and homing/targeting ligand to tumor microenvironment (TME) and lymphoid organs) from fused cells (of APCs and tumor cells) and immunoadjuvant. These HBNVs are efficiently internalized to the target cells, assisted in the maturation of APCs via antigens and adjuvant, activated the release of anti-tumor cytokines/inhibited the release of immunosuppressive cytokine, showed a homotypic effect on TME and lymph nodes, activated the anti-tumor immune cells/downregulated the immunosuppressive immune cells, reprogram the tumor microenvironment, and showed successful anti-tumor therapeutic and prophylactic effects.
{"title":"Fabrication and functional validation of a hybrid biomimetic nanovaccine (HBNV) against KitK641E-mutant melanoma","authors":"Kishwor Poudel , Zhenyu Ji , Ching-Ni Njauw , Anpuchchelvi Rajadurai , Brijesh Bhayana , Ryan J. Sullivan , Jong Oh Kim , Hensin Tsao","doi":"10.1016/j.bioactmat.2024.12.023","DOIUrl":"10.1016/j.bioactmat.2024.12.023","url":null,"abstract":"<div><div>Cancer nanovaccines hold the promise for personalization, precision, and pliability by integrating all the elements essential for effective immune stimulation. An effective immune response requires communication and interplay between antigen-presenting cells (APCs), tumor cells, and immune cells to stimulate, extend, and differentiate antigen-specific and non-specific anti-tumor immune cells. The versatility of nanomedicine can be adapted to deliver both immunoadjuvant payloads and antigens from the key players in immunity (i.e., APCs and tumor cells). The imperative for novel cancer medicine is particularly pressing for less common but more devastating KIT-mutated acral and mucosal melanomas that are resistant to small molecule c-kit and immune checkpoint inhibitors. To overcome this challenge, we successfully engineered nanotechnology-enabled hybrid biomimetic nanovaccine (HBNV) comprised of membrane proteins (antigens to activate immunity and homing/targeting ligand to tumor microenvironment (TME) and lymphoid organs) from fused cells (of APCs and tumor cells) and immunoadjuvant. These HBNVs are efficiently internalized to the target cells, assisted in the maturation of APCs via antigens and adjuvant, activated the release of anti-tumor cytokines/inhibited the release of immunosuppressive cytokine, showed a homotypic effect on TME and lymph nodes, activated the anti-tumor immune cells/downregulated the immunosuppressive immune cells, reprogram the tumor microenvironment, and showed successful anti-tumor therapeutic and prophylactic effects.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"46 ","pages":"Pages 347-364"},"PeriodicalIF":18.0,"publicationDate":"2024-12-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11742834/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999287","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}
Biodegradable magnesium (Mg) implant generally provides temporary fracture fixation and facilitates bone regeneration. However, the exact effects of generated Mg ions (Mg2+), hydrogen gas (H2), and hydroxide ions (OH-) by Mg degradation on enhancing fracture healing are not fully understood. Here we investigate the in vivo degradation of Mg intramedullary nail (Mg-IMN), revealing the generation of these degradation products around the fracture site during early stages. Bulk-RNA seq indicates that H2 and alkaline pH increase periosteal cell proliferation, while Mg2+ may mainly enhance extracellular matrix formation and cell adhesion in the femur ex vivo. In vivo studies further reveal that H2, Mg2+ and alkaline pH individually generate comparable effects to the enhanced bone regeneration in the Mg-IMN group. Mechanistically, the degradation products elevate sensory calcitonin gene-related peptide (CGRP) and simultaneously suppress adrenergic factors in newly formed bone. H2 and Mg2+, instead of alkaline pH, increase CGRP synthesis and inhibit adrenergic receptors. Our findings, for the first time, elucidate that Mg2+, H2, and alkaline pH environment generated by Mg-IMN act distinctly and synergistically mediated by the skeletal interoceptive regulation to accelerate bone regeneration. These findings may advance the understanding on biological functions of Mg-IMN in fracture repair and even other bone disorders.
{"title":"Degradation products of magnesium implant synergistically enhance bone regeneration: Unraveling the roles of hydrogen gas and alkaline environment","authors":"Yuanming An , Haozhi Zhang , Shi'an Zhang , Yuantao Zhang , Lizhen Zheng , Xin Chen , Wenxue Tong , Jiankun Xu , Ling Qin","doi":"10.1016/j.bioactmat.2024.12.020","DOIUrl":"10.1016/j.bioactmat.2024.12.020","url":null,"abstract":"<div><div>Biodegradable magnesium (Mg) implant generally provides temporary fracture fixation and facilitates bone regeneration. However, the exact effects of generated Mg ions (Mg<sup>2+</sup>), hydrogen gas (H<sub>2</sub>), and hydroxide ions (OH<sup>-</sup>) by Mg degradation on enhancing fracture healing are not fully understood. Here we investigate the <em>in vivo</em> degradation of Mg intramedullary nail (Mg-IMN), revealing the generation of these degradation products around the fracture site during early stages. Bulk-RNA seq indicates that H<sub>2</sub> and alkaline pH increase periosteal cell proliferation, while Mg<sup>2+</sup> may mainly enhance extracellular matrix formation and cell adhesion in the femur <em>ex vivo</em>. <em>In vivo</em> studies further reveal that H<sub>2</sub>, Mg<sup>2+</sup> and alkaline pH individually generate comparable effects to the enhanced bone regeneration in the Mg-IMN group. Mechanistically, the degradation products elevate sensory calcitonin gene-related peptide (CGRP) and simultaneously suppress adrenergic factors in newly formed bone. H<sub>2</sub> and Mg<sup>2+</sup>, instead of alkaline pH, increase CGRP synthesis and inhibit adrenergic receptors. Our findings, for the first time, elucidate that Mg<sup>2+</sup>, H<sub>2</sub>, and alkaline pH environment generated by Mg-IMN act distinctly and synergistically mediated by the skeletal interoceptive regulation to accelerate bone regeneration. These findings may advance the understanding on biological functions of Mg-IMN in fracture repair and even other bone disorders.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"46 ","pages":"Pages 331-346"},"PeriodicalIF":18.0,"publicationDate":"2024-12-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732853/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999278","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 : 2024-12-25DOI: 10.1016/j.bioactmat.2024.11.036
Wenhan Tian , Yuzeng Liu , Bo Han , Fengqi Cheng , Kang Yang , Weiyuan Hu , Dongdong Ye , Sujun Wu , Jiping Yang , Qi Chen , Yong Hai , Robert O. Ritchie , Guanping He , Juan Guan
Through millions of years of evolution, bones have developed a complex and elegant hierarchical structure, utilizing tropocollagen and hydroxyapatite to attain an intricate balance between modulus, strength, and toughness. In this study, continuous fiber silk composites (CFSCs) of large size are prepared to mimic the hierarchical structure of natural bones, through the inheritance of the hierarchical structure of fiber silk and the integration with a polyester matrix. Due to the robust interface between the matrix and fiber silk, CFSCs show maintained stable long-term mechanical performance under wet conditions. During in vivo degradation, this material primarily undergoes host cell-mediated surface degradation, rather than bulk hydrolysis. We demonstrate significant capabilities of CFSCs in promoting vascularization and macrophage differentiation toward repair. A bone defect model further indicates the potential of CFSC for bone graft applications. Our belief is that the material family of CFSCs may promise a novel biomaterial strategy for yet to be achieved excellent regenerative implants.
{"title":"Mechanically robust surface-degradable implant from fiber silk composites demonstrates regenerative potential","authors":"Wenhan Tian , Yuzeng Liu , Bo Han , Fengqi Cheng , Kang Yang , Weiyuan Hu , Dongdong Ye , Sujun Wu , Jiping Yang , Qi Chen , Yong Hai , Robert O. Ritchie , Guanping He , Juan Guan","doi":"10.1016/j.bioactmat.2024.11.036","DOIUrl":"10.1016/j.bioactmat.2024.11.036","url":null,"abstract":"<div><div>Through millions of years of evolution, bones have developed a complex and elegant hierarchical structure, utilizing tropocollagen and hydroxyapatite to attain an intricate balance between modulus, strength, and toughness. In this study, continuous fiber silk composites (CFSCs) of large size are prepared to mimic the hierarchical structure of natural bones, through the inheritance of the hierarchical structure of fiber silk and the integration with a polyester matrix. Due to the robust interface between the matrix and fiber silk, CFSCs show maintained stable long-term mechanical performance under wet conditions. During <em>in vivo</em> degradation, this material primarily undergoes host cell-mediated surface degradation, rather than bulk hydrolysis. We demonstrate significant capabilities of CFSCs in promoting vascularization and macrophage differentiation toward repair. A bone defect model further indicates the potential of CFSC for bone graft applications. Our belief is that the material family of CFSCs may promise a novel biomaterial strategy for yet to be achieved excellent regenerative implants.</div></div>","PeriodicalId":8762,"journal":{"name":"Bioactive Materials","volume":"45 ","pages":"Pages 584-598"},"PeriodicalIF":18.0,"publicationDate":"2024-12-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11732114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982579","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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