Pub Date : 2024-09-12DOI: 10.1016/j.mtbio.2024.101237
Diabetic foot ulcers, pressure ulcers, and bedsores can easily develop into chronic wounds with bacterial infections, complicating wound healing. This work reports a two-step strategy for treating infected chronic wounds. Firstly, LL37 mimetic peptide-W379 peptides were rapidly released to eliminate the bacterial biofilm on the wound. Then, 3D radially aligned nanofiber scaffolds loaded with W379 antimicrobial peptide and PDGF-BB were used to treat the wound to prevent bacterial infection recurrence and promote angiogenesis and granulation tissue regeneration, thereby accelerating wound healing. In the presented study, we found that the combined use of burst and controlled release of W379 antimicrobial peptide effectively clears the bacterial biofilm and prevents the recurrence of bacterial infection. Additionally, we found that the removal of the bacterial biofilm contributed to modulating the local inflammatory response from a pro-inflammatory type to a pro-regenerative type. Furthermore, the use of PDGF-BB significantly promotes neovascularization and granulation tissue regeneration in the wound bed, resulting in accelerating re-epithelialization and wound closure. Our study provides a promising treatment method for the repair of infected chronic wounds.
{"title":"A 3D radially aligned nanofiber scaffold co-loaded with LL37 mimetic peptide and PDGF-BB for the management of infected chronic wounds","authors":"","doi":"10.1016/j.mtbio.2024.101237","DOIUrl":"10.1016/j.mtbio.2024.101237","url":null,"abstract":"<div><p>Diabetic foot ulcers, pressure ulcers, and bedsores can easily develop into chronic wounds with bacterial infections, complicating wound healing. This work reports a two-step strategy for treating infected chronic wounds. Firstly, LL37 mimetic peptide-W379 peptides were rapidly released to eliminate the bacterial biofilm on the wound. Then, 3D radially aligned nanofiber scaffolds loaded with W379 antimicrobial peptide and PDGF-BB were used to treat the wound to prevent bacterial infection recurrence and promote angiogenesis and granulation tissue regeneration, thereby accelerating wound healing. In the presented study, we found that the combined use of burst and controlled release of W379 antimicrobial peptide effectively clears the bacterial biofilm and prevents the recurrence of bacterial infection. Additionally, we found that the removal of the bacterial biofilm contributed to modulating the local inflammatory response from a pro-inflammatory type to a pro-regenerative type. Furthermore, the use of PDGF-BB significantly promotes neovascularization and granulation tissue regeneration in the wound bed, resulting in accelerating re-epithelialization and wound closure. Our study provides a promising treatment method for the repair of infected chronic wounds.</p></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590006424002989/pdfft?md5=9db1fccfdc71ff755d256982b1bd59fa&pid=1-s2.0-S2590006424002989-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142232339","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 : 2024-09-12DOI: 10.1016/j.mtbio.2024.101235
The adipogenic property of decellularized adipose-derived matrix (DAM) varies widely across reports, making it difficult to make a horizontal comparison between reports and posing challenges for the stable clinical translation of DAM. It is possibly due to differences in donor characteristics, but the exact relationship remains unclear. Despite extensive research on the differences between superficial and deep layers of abdominal subcutaneous fat, a main donor of DAM, little is known about their extracellular matrix (ECM) which is promising in regenerative medicine. In this study, we first confirmed the distinct compositional profiles and adipogenic potential between superficial and deep DAM (S-DAM and D-DAM). Both in vitro and in vivo assays confirmed superior adipogenic induction potential in S-DAM over D-DAM. Total amounts of ECM proteins like collagen and laminin were similar, however, the predominant types differed, with collagen I dominating S-DAM and collagen XIV prevailing in D-DAM. S-DAM was enriched with mitochondrial and immunological proteins, whereas D-DAM featured more neuronal, vascular, muscular, and endocrine-related proteins. More proteins involved in mRNA processing were found in D-DAM, with Protein-Protein Interaction (PPI) analysis revealing HNRNPA2B1, HNRNPA1, and HNRNPC as the most tightly interacting members. These findings not only deepen our comprehension of the structural and functional heterogeneity of adipose tissues but also become one of the reason for the large variability between batches of DAM products, providing guidance for constructing more efficient and stable bio-scaffolds.
脱细胞脂肪衍生基质(DAM)的成脂特性在不同报道中差异很大,因此很难对不同报道进行横向比较,也给 DAM 稳定的临床转化带来了挑战。这可能是由于供体特征的差异造成的,但具体关系仍不清楚。腹部皮下脂肪是 DAM 的主要供体,尽管人们对腹部皮下脂肪浅层和深层的差异进行了大量研究,但对其细胞外基质(ECM)却知之甚少,而 ECM 在再生医学中大有可为。在这项研究中,我们首先证实了浅层和深层 DAM(S-DAM 和 D-DAM)之间不同的组成特征和成脂潜力。体外和体内试验都证实了 S-DAM 比 D-DAM 具有更高的诱导成脂潜力。胶原蛋白和层粘连蛋白等 ECM 蛋白的总量相似,但主要类型不同,胶原蛋白 I 在 S-DAM 中占主导地位,而胶原蛋白 XIV 在 D-DAM 中占主导地位。S-DAM富含线粒体和免疫蛋白,而D-DAM则含有更多神经元、血管、肌肉和内分泌相关蛋白。在 D-DAM 中发现了更多参与 mRNA 处理的蛋白质,蛋白质-蛋白质相互作用(PPI)分析显示 HNRNPA2B1、HNRNPA1 和 HNRNPC 是相互作用最紧密的成员。这些发现不仅加深了我们对脂肪组织结构和功能异质性的理解,而且也成为不同批次的 DAM 产品之间存在巨大差异的原因之一,为构建更高效、更稳定的生物支架提供了指导。
{"title":"Decellularized adipose-derived matrix from Superficial layers of abdominal adipose tissue exhibits superior capacity of adipogenesis compared to deep layers","authors":"","doi":"10.1016/j.mtbio.2024.101235","DOIUrl":"10.1016/j.mtbio.2024.101235","url":null,"abstract":"<div><p>The adipogenic property of decellularized adipose-derived matrix (DAM) varies widely across reports, making it difficult to make a horizontal comparison between reports and posing challenges for the stable clinical translation of DAM. It is possibly due to differences in donor characteristics, but the exact relationship remains unclear. Despite extensive research on the differences between superficial and deep layers of abdominal subcutaneous fat, a main donor of DAM, little is known about their extracellular matrix (ECM) which is promising in regenerative medicine. In this study, we first confirmed the distinct compositional profiles and adipogenic potential between superficial and deep DAM (S-DAM and D-DAM). Both in vitro and in vivo assays confirmed superior adipogenic induction potential in S-DAM over D-DAM. Total amounts of ECM proteins like collagen and laminin were similar, however, the predominant types differed, with collagen I dominating S-DAM and collagen XIV prevailing in D-DAM. S-DAM was enriched with mitochondrial and immunological proteins, whereas D-DAM featured more neuronal, vascular, muscular, and endocrine-related proteins. More proteins involved in mRNA processing were found in D-DAM, with Protein-Protein Interaction (PPI) analysis revealing HNRNPA2B1, HNRNPA1, and HNRNPC as the most tightly interacting members. These findings not only deepen our comprehension of the structural and functional heterogeneity of adipose tissues but also become one of the reason for the large variability between batches of DAM products, providing guidance for constructing more efficient and stable bio-scaffolds.</p></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590006424002965/pdfft?md5=a87afc1211964ece3544b154f2dbd0bf&pid=1-s2.0-S2590006424002965-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142243131","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 : 2024-09-11DOI: 10.1016/j.mtbio.2024.101240
Aristolochic acid I (AAI), a natural compound in aristolochia type Chinese medicinal herb, is generally acknowledged to have nephrotoxicity, which may be associated with mitophagy. Mitophagy is a cellular process with important functions that drive AAI-induced renal injury. Mitochondrial pH is currently measured by fluorescent probes in cell culture, but existing probes do not allow for in situ imaging of AAI-induced mitophagy in vivo. We developed a ratiometric fluorescent/PA dual-modal probe with a silicon rhodamine fluorophore and a pH-sensitive hemicyanine dye covalently linked via a short chain to obtain a FRET type probe. The probe was used to measure AAI-mediated mitochondrial acidification in live cells and in vivo. The Förster resonance energy transfer (FRET)-mediated ratiometric and bimodal method can efficiently eliminate signal variability associated with the commonly used one-emission and single detection mode by ratiometric two channels of the donor and acceptor. The probe has good water-solubility and low molecular weight with two positively charged, facilitating its precise targeting into renal mitochondria, where the fluorescent/PA changes in response to mitochondrial acidification, enabling dynamic and semi-quantitative mapping of subtle changes in mitochondrial pH in AAI-induced nephrotoxicity mouse model for the first time. Also, the joint use of L-carnitine could mitigate the mitophagy in AAI-induced nephrotoxicity.
{"title":"In vivo targeted-imaging of mitochondrial acidification in an aristolochic acid I-induced nephrotoxicity mouse model by a fluorescent/photoacoustic bimodal probe","authors":"","doi":"10.1016/j.mtbio.2024.101240","DOIUrl":"10.1016/j.mtbio.2024.101240","url":null,"abstract":"<div><p>Aristolochic acid I (AAI), a natural compound in aristolochia type Chinese medicinal herb, is generally acknowledged to have nephrotoxicity, which may be associated with mitophagy. Mitophagy is a cellular process with important functions that drive AAI-induced renal injury. Mitochondrial pH is currently measured by fluorescent probes in cell culture, but existing probes do not allow for in situ imaging of AAI-induced mitophagy in vivo. We developed a ratiometric fluorescent/PA dual-modal probe with a silicon rhodamine fluorophore and a pH-sensitive hemicyanine dye covalently linked via a short chain to obtain a FRET type probe. The probe was used to measure AAI-mediated mitochondrial acidification in live cells and in vivo. The Förster resonance energy transfer (FRET)-mediated ratiometric and bimodal method can efficiently eliminate signal variability associated with the commonly used one-emission and single detection mode by ratiometric two channels of the donor and acceptor. The probe has good water-solubility and low molecular weight with two positively charged, facilitating its precise targeting into renal mitochondria, where the fluorescent/PA changes in response to mitochondrial acidification, enabling dynamic and semi-quantitative mapping of subtle changes in mitochondrial pH in AAI-induced nephrotoxicity mouse model for the first time. Also, the joint use of L-carnitine could mitigate the mitophagy in AAI-induced nephrotoxicity.</p></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590006424003016/pdfft?md5=06839d4d87b8973e74ad4bf8992f6a8a&pid=1-s2.0-S2590006424003016-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142171849","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 : 2024-09-10DOI: 10.1016/j.mtbio.2024.101232
Tuberculosis (TB) remains the leading cause of deaths among infectious diseases worldwide. Cutaneous Tuberculosis (CTB), caused by Mycobacterium tuberculosis (Mtb) infection in the skin, is still a harmful public health issue that requires more effective treatment strategy. Herein, we introduced mannose-modified mesoporous polydopamine nanosystems (Man-mPDA NPs) as the macrophage-targeted vectors to deliver anti-TB drug rifampicin and as photothermal agent to facilitate photothermal therapy (PTT) against Mtb infected macrophages for synergistic treatment of CTB. Based on the selective macrophage targeting effects, the proposed Rif@Man-mPDA NPs also showed excellent photothermal properties to develop Rif@Man-mPDA NPs-mediated PTT for intracellular Mtb killings in macrophages. Importantly, Rif@Man-mPDA NPs could inhibit the immune escape of Mtb by effectively chelating intracellular Fe2+ and inhibiting lipid peroxidation, and up-regulating GPX4 expression to inhibit ferroptosis of Mtb infected macrophages through activating Nrf2/HO-1 signaling. Moreover, Rif@Man-mPDA NPs-mediated PTT could effectively activate host cell immune responses by promoting autophagy of Mtb infected macrophages, which thus synergizes targeted drug delivery and ferroptosis inhibition for more effective intracellular Mtb clearance. This Rif@Man-mPDA NPs-mediated PTT strategy could also effectively inhibit the Mtb burdens and alleviate the pathological lesions induced by Mtb infection without significant systemic side effects in mouse CTB model. These results indicate that Rif@Man-mPDA NPs-mediated PTT can be served as a novel anti-TB strategy against CTB by synergizing macrophage targeted photothermal therapy and host immune defenses, thus holding promise for more effective treatment strategy development against CTB.
{"title":"Photothermal and host immune activated therapy of cutaneous tuberculosis using macrophage targeted mesoporous polydopamine nanoparticles","authors":"","doi":"10.1016/j.mtbio.2024.101232","DOIUrl":"10.1016/j.mtbio.2024.101232","url":null,"abstract":"<div><p>Tuberculosis (TB) remains the leading cause of deaths among infectious diseases worldwide. Cutaneous Tuberculosis (CTB), caused by <em>Mycobacterium tuberculosis</em> (Mtb) infection in the skin, is still a harmful public health issue that requires more effective treatment strategy. Herein, we introduced mannose-modified mesoporous polydopamine nanosystems (Man-mPDA NPs) as the macrophage-targeted vectors to deliver anti-TB drug rifampicin and as photothermal agent to facilitate photothermal therapy (PTT) against Mtb infected macrophages for synergistic treatment of CTB. Based on the selective macrophage targeting effects, the proposed Rif@Man-mPDA NPs also showed excellent photothermal properties to develop Rif@Man-mPDA NPs-mediated PTT for intracellular Mtb killings in macrophages. Importantly, Rif@Man-mPDA NPs could inhibit the immune escape of Mtb by effectively chelating intracellular Fe<sup>2+</sup> and inhibiting lipid peroxidation, and up-regulating GPX4 expression to inhibit ferroptosis of Mtb infected macrophages through activating Nrf2/HO-1 signaling. Moreover, Rif@Man-mPDA NPs-mediated PTT could effectively activate host cell immune responses by promoting autophagy of Mtb infected macrophages, which thus synergizes targeted drug delivery and ferroptosis inhibition for more effective intracellular Mtb clearance. This Rif@Man-mPDA NPs-mediated PTT strategy could also effectively inhibit the Mtb burdens and alleviate the pathological lesions induced by Mtb infection without significant systemic side effects in mouse CTB model. These results indicate that Rif@Man-mPDA NPs-mediated PTT can be served as a novel anti-TB strategy against CTB by synergizing macrophage targeted photothermal therapy and host immune defenses, thus holding promise for more effective treatment strategy development against CTB.</p></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S259000642400293X/pdfft?md5=3124cc145eb4d529882369fbefc0d04f&pid=1-s2.0-S259000642400293X-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142228960","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 : 2024-09-08DOI: 10.1016/j.mtbio.2024.101234
Magnesium (Mg)-based scaffolds are garnering increasing attention as bone repair materials owing to their biodegradability and mechanical resemblance to natural bone. Their effectiveness can be augmented by incorporating surface coatings to meet clinical needs. However, the limited bonding strength and unclear mechanisms of these coatings have impeded the clinical utility of scaffolds. To address these issues, this study introduces a composite coating of high-bonding-strength polydopamine-microarc oxidation (PDA-MHA) on Mg-based scaffolds. The results showed that the PDA-MHA coating achieved a bonding strength of 40.56 ± 1.426 MPa with the Mg scaffold surface, effectively enhancing hydrophilicity and controlling degradation rates. Furthermore, the scaffold facilitated bone regeneration by influencing osteogenic markers such as RUNX-2, OPN, OCN, and VEGF. Transcriptomic analyses further demonstrated that the PDA-MHA/Mg scaffold upregulated carboxypeptidase Z expression and activated the Wnt-4/β-catenin signaling pathway, thereby promoting bone regeneration. Overall, this study demonstrated that PDA can synergistically enhance bone repair with Mg scaffold, broadening the application scenarios of Mg and PDA in the field of biomaterials. Moreover, this study provides a theoretical underpinning for the application and clinical translation of Mg-based scaffolds in bone tissue engineering endeavors.
{"title":"Analysis of the CPZ/Wnt4 osteogenic pathway for high-bonding-strength composite-coated magnesium scaffolds through transcriptomics","authors":"","doi":"10.1016/j.mtbio.2024.101234","DOIUrl":"10.1016/j.mtbio.2024.101234","url":null,"abstract":"<div><p>Magnesium (Mg)-based scaffolds are garnering increasing attention as bone repair materials owing to their biodegradability and mechanical resemblance to natural bone. Their effectiveness can be augmented by incorporating surface coatings to meet clinical needs. However, the limited bonding strength and unclear mechanisms of these coatings have impeded the clinical utility of scaffolds. To address these issues, this study introduces a composite coating of high-bonding-strength polydopamine-microarc oxidation (PDA-MHA) on Mg-based scaffolds. The results showed that the PDA-MHA coating achieved a bonding strength of 40.56 ± 1.426 MPa with the Mg scaffold surface, effectively enhancing hydrophilicity and controlling degradation rates. Furthermore, the scaffold facilitated bone regeneration by influencing osteogenic markers such as RUNX-2, OPN, OCN, and VEGF. Transcriptomic analyses further demonstrated that the PDA-MHA/Mg scaffold upregulated carboxypeptidase Z expression and activated the Wnt-4/β-catenin signaling pathway, thereby promoting bone regeneration. Overall, this study demonstrated that PDA can synergistically enhance bone repair with Mg scaffold, broadening the application scenarios of Mg and PDA in the field of biomaterials. Moreover, this study provides a theoretical underpinning for the application and clinical translation of Mg-based scaffolds in bone tissue engineering endeavors.</p></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590006424002953/pdfft?md5=cbd8c88ae2d1d7547dd1d6856f2511da&pid=1-s2.0-S2590006424002953-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142161706","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 : 2024-09-06DOI: 10.1016/j.mtbio.2024.101225
Wear particles produced by joint replacements induce inflammatory responses that lead to periprosthetic osteolysis and aseptic loosening. However, the precise mechanisms driving wear particle-induced osteolysis are not fully understood. Recent evidence suggests that autophagy, a cellular degradation process, plays a significant role in this pathology. This study aimed to clarify the role of autophagy in mediating inflammation and osteolysis triggered by wear particles and to evaluate the therapeutic potential of zinc oxide nanoparticles (ZnO NPs).
We incorporated ZnO into the prosthetic material itself, ensuring that the wear particles inherently carried ZnO, providing a targeted and sustained intervention. Our findings reveal that polymer wear particles induce excessive autophagic activity, which is closely associated with increased inflammation and osteolysis. We identified secretory autophagy as a key mechanism for IL-1β secretion, exacerbating osteolysis. Both in vitro and in vivo experiments demonstrated that ZnO-doped particles significantly inhibit autophagic overactivation, thereby reducing inflammation and osteolysis.
In summary, this study establishes secretory autophagy as a critical mechanism in wear particle-induced osteolysis and highlights the potential of ZnO-doped prosthetic polymers for targeted, sustained mitigation of periprosthetic osteolysis.
{"title":"Nanoscale ZnO doping in prosthetic polymers mitigate wear particle-induced inflammation and osteolysis through inhibiting macrophage secretory autophagy","authors":"","doi":"10.1016/j.mtbio.2024.101225","DOIUrl":"10.1016/j.mtbio.2024.101225","url":null,"abstract":"<div><p>Wear particles produced by joint replacements induce inflammatory responses that lead to periprosthetic osteolysis and aseptic loosening. However, the precise mechanisms driving wear particle-induced osteolysis are not fully understood. Recent evidence suggests that autophagy, a cellular degradation process, plays a significant role in this pathology. This study aimed to clarify the role of autophagy in mediating inflammation and osteolysis triggered by wear particles and to evaluate the therapeutic potential of zinc oxide nanoparticles (ZnO NPs).</p><p>We incorporated ZnO into the prosthetic material itself, ensuring that the wear particles inherently carried ZnO, providing a targeted and sustained intervention. Our findings reveal that polymer wear particles induce excessive autophagic activity, which is closely associated with increased inflammation and osteolysis. We identified secretory autophagy as a key mechanism for IL-1β secretion, exacerbating osteolysis. Both <em>in vitro</em> and <em>in vivo</em> experiments demonstrated that ZnO-doped particles significantly inhibit autophagic overactivation, thereby reducing inflammation and osteolysis.</p><p>In summary, this study establishes secretory autophagy as a critical mechanism in wear particle-induced osteolysis and highlights the potential of ZnO-doped prosthetic polymers for targeted, sustained mitigation of periprosthetic osteolysis.</p></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590006424002862/pdfft?md5=a403a749ace0b3a3e357f846b5acdcae&pid=1-s2.0-S2590006424002862-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142168008","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 : 2024-09-06DOI: 10.1016/j.mtbio.2024.101226
Synthetic biology primarily uses genetic engineering to control living cells. In contrast, recent work has ushered in the architectural engineering of living cells through intracellular materials. Specifically, Cyborg Bacteria are created by incorporating synthetic PEG-based hydrogel inside cells. Cyborg Bacteria do not replicate but maintain essential cellular functions, including metabolism and protein synthesis. Thus far, Cyborg Bacteria have been engineered using one primary composition of intracellular hydrogel components. Here, we demonstrate the versatility of controlling the physical and biochemical aspects of Cyborg Bacteria using different structures of hydrogels. The intracellular cell-gel architecture is modulated using a different photoinitiator, PEG-diacrylate (PEG-DA) of different molecular weights, 4arm PEG-DA, and dsDNA-PEG. We show that the molecular weight of the PEG-DA affects the generation and metabolism of Cyborg Bacteria. In addition, we show that the hybrid dsDNA-PEG intracellular hydrogel controls protein expression levels of the Cyborg Bacteria through post-transcriptional regulation and polymerase sequestration. Our work creates a new frontier of modulating intracellular gel components to control Cyborg Bacteria function and architecture.
{"title":"Architectural engineering of Cyborg Bacteria with intracellular hydrogel","authors":"","doi":"10.1016/j.mtbio.2024.101226","DOIUrl":"10.1016/j.mtbio.2024.101226","url":null,"abstract":"<div><p>Synthetic biology primarily uses genetic engineering to control living cells. In contrast, recent work has ushered in the architectural engineering of living cells through intracellular materials. Specifically, Cyborg Bacteria are created by incorporating synthetic PEG-based hydrogel inside cells. Cyborg Bacteria do not replicate but maintain essential cellular functions, including metabolism and protein synthesis. Thus far, Cyborg Bacteria have been engineered using one primary composition of intracellular hydrogel components. Here, we demonstrate the versatility of controlling the physical and biochemical aspects of Cyborg Bacteria using different structures of hydrogels. The intracellular cell-gel architecture is modulated using a different photoinitiator, PEG-diacrylate (PEG-DA) of different molecular weights, 4arm PEG-DA, and dsDNA-PEG. We show that the molecular weight of the PEG-DA affects the generation and metabolism of Cyborg Bacteria. In addition, we show that the hybrid dsDNA-PEG intracellular hydrogel controls protein expression levels of the Cyborg Bacteria through post-transcriptional regulation and polymerase sequestration. Our work creates a new frontier of modulating intracellular gel components to control Cyborg Bacteria function and architecture.</p></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590006424002874/pdfft?md5=729f5d80a40992007d8084e7c5e02a99&pid=1-s2.0-S2590006424002874-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142242377","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 : 2024-09-04DOI: 10.1016/j.mtbio.2024.101224
In this research, the spinnability of bioactive glass (BG) precursor solution was supplied by alkoxysilane sol with appropriate molar ratio of H2O/silicon (R) to prepare bioactive glass fiber membrane (BFM) using electrospinning (ES) technique. Alkoxysilane could form a linear or chain-like colloidal aggregation in hydrolysis-polycondensation with R = 2 or so, thereby exhibiting good spinnability. Therefore, the role of polymer binders could be largely replaced. Due to the significant decrease of polymer binder, the defects within the fibers are largely reduced and degree of fiber densification was improved after calcination, leading to BFM drastically enhanced strength and flexibility. The effect of R and calcination temperature on mechanical performance were investigated in detail. The tensile strength could reach the highest value 2.31 MPa with R = 2 and calcination at 700 °C. In addition, under this preparation condition, the BFM also possessed good flexibility with bending rigidity 37.7 mN. Furthermore, the great performance of promoting cell proliferation and osteogenesis could be observed from in vitro cellular experiment. The BFM calcined at 750 °C exhibited the best promoting osteogenic differentiation ability. The rat skull defect model revealed BFM could perform well in osteogenesis in vivo.
本研究采用烷氧基硅烷溶胶(H2O/硅(R)的摩尔比适当)提供生物活性玻璃(BG)前体溶液的可纺性,利用电纺丝(ES)技术制备生物活性玻璃纤维膜(BFM)。烷氧基硅烷可在 R = 2 左右的水解缩聚过程中形成线状或链状胶体聚集,从而表现出良好的可纺性。因此,聚合物粘合剂的作用在很大程度上可以被取代。由于聚合物粘合剂的显著减少,煅烧后纤维内部的缺陷大大减少,纤维致密化程度得到改善,从而使 BFM 的强度和柔韧性大幅提高。详细研究了 R 和煅烧温度对力学性能的影响。当 R = 2 且煅烧温度为 700 ℃ 时,拉伸强度达到最高值 2.31 MPa。此外,在这种制备条件下,BFM 还具有良好的柔韧性,弯曲刚度为 37.7 mN。此外,从体外细胞实验中还可以观察到该材料在促进细胞增殖和成骨方面的优异性能。750 °C 煅烧的 BFM 具有最佳的促进成骨分化能力。大鼠颅骨缺损模型显示,BFM 在体内成骨方面表现良好。
{"title":"Flexible and high-strength bioactive glass fiber membrane for bone regeneration with the aid of alkoxysilane sol spinnability","authors":"","doi":"10.1016/j.mtbio.2024.101224","DOIUrl":"10.1016/j.mtbio.2024.101224","url":null,"abstract":"<div><p>In this research, the spinnability of bioactive glass (BG) precursor solution was supplied by alkoxysilane sol with appropriate molar ratio of H<sub>2</sub>O/silicon (R) to prepare bioactive glass fiber membrane (BFM) using electrospinning (ES) technique. Alkoxysilane could form a linear or chain-like colloidal aggregation in hydrolysis-polycondensation with R = 2 or so, thereby exhibiting good spinnability. Therefore, the role of polymer binders could be largely replaced. Due to the significant decrease of polymer binder, the defects within the fibers are largely reduced and degree of fiber densification was improved after calcination, leading to BFM drastically enhanced strength and flexibility. The effect of R and calcination temperature on mechanical performance were investigated in detail. The tensile strength could reach the highest value 2.31 MPa with R = 2 and calcination at 700 °C. In addition, under this preparation condition, the BFM also possessed good flexibility with bending rigidity 37.7 mN. Furthermore, the great performance of promoting cell proliferation and osteogenesis could be observed from <em>in vitro</em> cellular experiment. The BFM calcined at 750 °C exhibited the best promoting osteogenic differentiation ability. The rat skull defect model revealed BFM could perform well in osteogenesis <em>in vivo</em>.</p></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590006424002850/pdfft?md5=04e275029d211e3ac13baceef1989f0b&pid=1-s2.0-S2590006424002850-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142151923","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 : 2024-09-04DOI: 10.1016/j.mtbio.2024.101230
Age-related macular degeneration (AMD) is the leading cause of blindness among elderly people worldwide. However, there are currently no effective treatments for AMD. Oxidative stress-induced retinal pigment epithelium (RPE) degeneration and the inflammatory response are the main causes of AMD. In this study, a polyethylene glycol (PEG)-coated rhodium nanozyme (PEG-RhZ) with excellent reactive oxygen species (ROS) and reactive nitrogen species (RNS) elimination capability was synthesized for the treatment of AMD. PEG-RhZs protected RPE cell viability and barrier function upon exposure to oxidative stress stimuli. Additionally, microglial migration and iNOS, IL-1β and TNF-α expression were inhibited by PEG-RhZs. In the acute phase of the AMD model, PEG-RhZs significantly alleviated RPE oxidative damage and inhibited microglial activation. In the late stage of the AMD model, PEG-RhZs reduced photoreceptor loss and improved vision impairment. Furthermore, PEG-RhZs showed good biocompatibility and stability both in vitro and in vivo. Collectively, our findings suggest the therapeutic potential of PEG-RhZs for AMD treatment.
STATEMENT OF SIGNIFICANCE: AMD is a kind of retinal degenerative disease that poses heavy health burden globally. PEG-RhZs exhibiting robust ROS and RNS scavenging capabilities have shown promise in safeguarding retinal pigment epithelium (RPE) from oxidative stress, suppressing microglia activation and the secretion of pro-inflammatory molecules, mitigating loss of retinal photoreceptor cells, and ameliorating visual impairment. The commendable antioxidant properties, biological safety, and biostability of PEG-RhZs offer valuable insights for the clinical management of AMD.
{"title":"Rhodium nanozyme mitigates RPE degeneration and preserves vision in age-related macular degeneration via antioxidant and anti-inflammatory mechanisms","authors":"","doi":"10.1016/j.mtbio.2024.101230","DOIUrl":"10.1016/j.mtbio.2024.101230","url":null,"abstract":"<div><p>Age-related macular degeneration (AMD) is the leading cause of blindness among elderly people worldwide. However, there are currently no effective treatments for AMD. Oxidative stress-induced retinal pigment epithelium (RPE) degeneration and the inflammatory response are the main causes of AMD. In this study, a polyethylene glycol (PEG)-coated rhodium nanozyme (PEG-RhZ) with excellent reactive oxygen species (ROS) and reactive nitrogen species (RNS) elimination capability was synthesized for the treatment of AMD. PEG-RhZs protected RPE cell viability and barrier function upon exposure to oxidative stress stimuli. Additionally, microglial migration and iNOS, IL-1β and TNF-α expression were inhibited by PEG-RhZs. In the acute phase of the AMD model, PEG-RhZs significantly alleviated RPE oxidative damage and inhibited microglial activation. In the late stage of the AMD model, PEG-RhZs reduced photoreceptor loss and improved vision impairment. Furthermore, PEG-RhZs showed good biocompatibility and stability both <em>in vitro</em> and <em>in vivo</em>. Collectively, our findings suggest the therapeutic potential of PEG-RhZs for AMD treatment.</p><p>STATEMENT OF SIGNIFICANCE: AMD is a kind of retinal degenerative disease that poses heavy health burden globally. PEG-RhZs exhibiting robust ROS and RNS scavenging capabilities have shown promise in safeguarding retinal pigment epithelium (RPE) from oxidative stress, suppressing microglia activation and the secretion of pro-inflammatory molecules, mitigating loss of retinal photoreceptor cells, and ameliorating visual impairment. The commendable antioxidant properties, biological safety, and biostability of PEG-RhZs offer valuable insights for the clinical management of AMD.</p></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590006424002916/pdfft?md5=b330b13164d425291781a9129954b8a2&pid=1-s2.0-S2590006424002916-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142151946","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 : 2024-09-04DOI: 10.1016/j.mtbio.2024.101229
Glaucoma presents a significant global health concern and affects millions of individuals worldwide and predicted a high increase in prevalence of about 111 million by 2040. The current standard treatment involves hypotensive eye drops; however, challenges such as patient adherence and limited drug bioavailability hinder the treatment effectiveness. Nanopharmaceuticals or nanomedicines offer promising solutions to overcome these obstacles. In this manuscript, we summarized the current limitations of conventional antiglaucoma treatment, role of nanomedicine in glaucoma treatment, rational design, factors effecting the performance of nanomedicine and different types of nanocarriers in designing of nanomedicine along with their applications in glaucoma treatment from recent literature. Current clinical challenges that hinder real-time application of antiglaucoma nanomedicine are highlighted. Lastly, future directions are identified for improving the therapeutic potential and translation of antiglaucoma nanomedicine into clinic.
{"title":"Nanomedicine in glaucoma treatment; Current challenges and future perspectives","authors":"","doi":"10.1016/j.mtbio.2024.101229","DOIUrl":"10.1016/j.mtbio.2024.101229","url":null,"abstract":"<div><p>Glaucoma presents a significant global health concern and affects millions of individuals worldwide and predicted a high increase in prevalence of about 111 million by 2040. The current standard treatment involves hypotensive eye drops; however, challenges such as patient adherence and limited drug bioavailability hinder the treatment effectiveness. Nanopharmaceuticals or nanomedicines offer promising solutions to overcome these obstacles. In this manuscript, we summarized the current limitations of conventional antiglaucoma treatment, role of nanomedicine in glaucoma treatment, rational design, factors effecting the performance of nanomedicine and different types of nanocarriers in designing of nanomedicine along with their applications in glaucoma treatment from recent literature. Current clinical challenges that hinder real-time application of antiglaucoma nanomedicine are highlighted. Lastly, future directions are identified for improving the therapeutic potential and translation of antiglaucoma nanomedicine into clinic.</p></div>","PeriodicalId":18310,"journal":{"name":"Materials Today Bio","volume":null,"pages":null},"PeriodicalIF":8.7,"publicationDate":"2024-09-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2590006424002904/pdfft?md5=15f96ff15250ec5d051214664a8441b3&pid=1-s2.0-S2590006424002904-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142151924","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}