Pub Date : 2022-04-28DOI: 10.1088/1748-605X/ac6b71
S. Çakal, Carmen Radeke, Juan F Alcala, D. Ellman, Sarkhan Butdayev, D. C. Andersen, K. Calloe, Johan U. Lind
Preclinical biomedical and pharmaceutical research on disease causes, drug targets, and side effects increasingly relies on in vitro models of human tissue. 3D printing offers unique opportunities for generating models of superior physiological accuracy, as well as for automating their fabrication. Towards these goals, we here describe a simple and scalable methodology for generating physiologically relevant models of skeletal muscle. Our approach relies on dual-material micro-extrusion of two types of gelatin hydrogel into patterned soft substrates with locally alternating stiffness. We identify minimally complex patterns capable of guiding the large-scale self-assembly of aligned, extended, and contractile human and murine skeletal myotubes. Interestingly, we find high-resolution patterning is not required, as even patterns with feature sizes of several hundred micrometers is sufficient. Consequently, the procedure is rapid and compatible with any low-cost extrusion-based 3D printer. The generated myotubes easily span several millimeters, and various myotube patterns can be generated in a predictable and reproducible manner. The compliant nature and adjustable thickness of the hydrogel substrates, serves to enable extended culture of contractile myotubes. The method is further readily compatible with standard cell-culturing platforms as well as commercially available electrodes for electrically induced exercise and monitoring of the myotubes.
{"title":"A simple and scalable 3D printing methodology for generating aligned and extended human and murine skeletal muscle tissues","authors":"S. Çakal, Carmen Radeke, Juan F Alcala, D. Ellman, Sarkhan Butdayev, D. C. Andersen, K. Calloe, Johan U. Lind","doi":"10.1088/1748-605X/ac6b71","DOIUrl":"https://doi.org/10.1088/1748-605X/ac6b71","url":null,"abstract":"Preclinical biomedical and pharmaceutical research on disease causes, drug targets, and side effects increasingly relies on in vitro models of human tissue. 3D printing offers unique opportunities for generating models of superior physiological accuracy, as well as for automating their fabrication. Towards these goals, we here describe a simple and scalable methodology for generating physiologically relevant models of skeletal muscle. Our approach relies on dual-material micro-extrusion of two types of gelatin hydrogel into patterned soft substrates with locally alternating stiffness. We identify minimally complex patterns capable of guiding the large-scale self-assembly of aligned, extended, and contractile human and murine skeletal myotubes. Interestingly, we find high-resolution patterning is not required, as even patterns with feature sizes of several hundred micrometers is sufficient. Consequently, the procedure is rapid and compatible with any low-cost extrusion-based 3D printer. The generated myotubes easily span several millimeters, and various myotube patterns can be generated in a predictable and reproducible manner. The compliant nature and adjustable thickness of the hydrogel substrates, serves to enable extended culture of contractile myotubes. The method is further readily compatible with standard cell-culturing platforms as well as commercially available electrodes for electrically induced exercise and monitoring of the myotubes.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2022-04-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44117936","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-27DOI: 10.1088/1748-605X/ac6b04
Xingwu Mo, Liliang Ouyang, Zhuo Xiong, Ting Zhang
Hydrogels, three-dimensional (3D) networks of hydrophilic polymers formed in water, are a significant type of soft matter used in fundamental and applied sciences. Hydrogels are of particular interest for biomedical applications, owing to their soft elasticity and good biocompatibility. However, the high water content and soft nature of hydrogels often make it difficult to process them into desirable solid forms. The development of 3D printing (3DP) technologies has provided opportunities for the manufacturing of hydrogels, by adopting a freeform fabrication method. Owing to its high printing speed and resolution, vat photopolymerization 3DP has recently attracted considerable interest for hydrogel fabrication, with digital light processing (DLP) becoming a widespread representative technique. Whilst acknowledging that other types of vat photopolymerization 3DP have also been applied for this purpose, we here only focus on DLP and its derivatives. In this review, we first comprehensively outline the most recent advances in both materials and fabrication, including the adaptation of novel hydrogel systems and advances in processing (e.g. volumetric printing and multimaterial integration). Secondly, we summarize the applications of hydrogel DLP, including regenerative medicine, functional microdevices, and soft robotics. To the best of our knowledge, this is the first time that either of these specific review focuses has been adopted in the literature. More importantly, we discuss the major challenges associated with hydrogel DLP and provide our perspectives on future trends. To summarize, this review aims to aid and inspire other researchers investigatng DLP, photocurable hydrogels, and the research fields related to them.
{"title":"Advances in digital light processing of hydrogels","authors":"Xingwu Mo, Liliang Ouyang, Zhuo Xiong, Ting Zhang","doi":"10.1088/1748-605X/ac6b04","DOIUrl":"https://doi.org/10.1088/1748-605X/ac6b04","url":null,"abstract":"Hydrogels, three-dimensional (3D) networks of hydrophilic polymers formed in water, are a significant type of soft matter used in fundamental and applied sciences. Hydrogels are of particular interest for biomedical applications, owing to their soft elasticity and good biocompatibility. However, the high water content and soft nature of hydrogels often make it difficult to process them into desirable solid forms. The development of 3D printing (3DP) technologies has provided opportunities for the manufacturing of hydrogels, by adopting a freeform fabrication method. Owing to its high printing speed and resolution, vat photopolymerization 3DP has recently attracted considerable interest for hydrogel fabrication, with digital light processing (DLP) becoming a widespread representative technique. Whilst acknowledging that other types of vat photopolymerization 3DP have also been applied for this purpose, we here only focus on DLP and its derivatives. In this review, we first comprehensively outline the most recent advances in both materials and fabrication, including the adaptation of novel hydrogel systems and advances in processing (e.g. volumetric printing and multimaterial integration). Secondly, we summarize the applications of hydrogel DLP, including regenerative medicine, functional microdevices, and soft robotics. To the best of our knowledge, this is the first time that either of these specific review focuses has been adopted in the literature. More importantly, we discuss the major challenges associated with hydrogel DLP and provide our perspectives on future trends. To summarize, this review aims to aid and inspire other researchers investigatng DLP, photocurable hydrogels, and the research fields related to them.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2022-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43745033","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bioactive glasses (BG) have been widely utilized as a biomaterial for bone repair. However, the early angiogenesis of BG may be inadequate, which weakens its osteogenic effects in large-sized bone defects and often leads to the failure of bone regeneration. In this study, we explored the effects of photobiomodulation (PBM) combined with BG on early angiogenesis to solve this bottleneck problem of insufficient early angiogenesis. In vitro, human umbilical vein endothelial cells (HUVECs) were cultured with BG extracts and treated with PBM using 1 J cm−2. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) and tubule formation assay were utilized to detect HUVECs’ proliferation, vascular growth factor genes expression and tubules formation. In vivo, bone defects at the femoral metaphysis in Sprague-Dawley rats were treated with BG particulates and PBM at 120 J cm−2. Hematoxylin–eosin staining was used to observe the inflammatory response, tissue formation and biomaterial absorption of bone defects. Immunohistochemical staining was applied to observe the vascular-like structure formation. The in vitro results showed that PBM combined with BG significantly promoted HUVECs’ proliferation, genes expression and mature tubules formation. On days 2, 4 and 7, the mRNA expression of VEGF in BG + PBM group was 2.70-, 2.59- and 3.05-fold higher than control (P< 0.05), and significantly higher than PBM and BG groups (P< 0.05). On days 4 and 7, the bFGF gene expression in BG + PBM group was 2.42- and 1.82-fold higher than control (P< 0.05), and also higher than PBM and BG groups (P< 0.05). Tube formation assay showed that mature tubules were formed in BG + PBM and PBM groups after 4 h, and the number in BG + PBM group was significantly higher than other groups (P< 0.05). In vivo results further confirmed PBM induced early angiogenesis, with more vascular-like structures observed in BG + PBM and PBM groups 2 week post-surgery. With the optimum PBM fluence and BG concentration, PBM combined with BG exerted additive effects on enhancing early angiogenesis.
{"title":"The additive effects of photobiomodulation and bioactive glasses on enhancing early angiogenesis","authors":"Lidong Huang, W. Gong, Gui-qin Huang, Jingyi Li, Jilin Wu, Yuguang Wang, Yanmei Dong","doi":"10.1088/1748-605X/ac6b07","DOIUrl":"https://doi.org/10.1088/1748-605X/ac6b07","url":null,"abstract":"Bioactive glasses (BG) have been widely utilized as a biomaterial for bone repair. However, the early angiogenesis of BG may be inadequate, which weakens its osteogenic effects in large-sized bone defects and often leads to the failure of bone regeneration. In this study, we explored the effects of photobiomodulation (PBM) combined with BG on early angiogenesis to solve this bottleneck problem of insufficient early angiogenesis. In vitro, human umbilical vein endothelial cells (HUVECs) were cultured with BG extracts and treated with PBM using 1 J cm−2. The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, real-time reverse transcription-polymerase chain reaction (real-time RT-PCR) and tubule formation assay were utilized to detect HUVECs’ proliferation, vascular growth factor genes expression and tubules formation. In vivo, bone defects at the femoral metaphysis in Sprague-Dawley rats were treated with BG particulates and PBM at 120 J cm−2. Hematoxylin–eosin staining was used to observe the inflammatory response, tissue formation and biomaterial absorption of bone defects. Immunohistochemical staining was applied to observe the vascular-like structure formation. The in vitro results showed that PBM combined with BG significantly promoted HUVECs’ proliferation, genes expression and mature tubules formation. On days 2, 4 and 7, the mRNA expression of VEGF in BG + PBM group was 2.70-, 2.59- and 3.05-fold higher than control (P< 0.05), and significantly higher than PBM and BG groups (P< 0.05). On days 4 and 7, the bFGF gene expression in BG + PBM group was 2.42- and 1.82-fold higher than control (P< 0.05), and also higher than PBM and BG groups (P< 0.05). Tube formation assay showed that mature tubules were formed in BG + PBM and PBM groups after 4 h, and the number in BG + PBM group was significantly higher than other groups (P< 0.05). In vivo results further confirmed PBM induced early angiogenesis, with more vascular-like structures observed in BG + PBM and PBM groups 2 week post-surgery. With the optimum PBM fluence and BG concentration, PBM combined with BG exerted additive effects on enhancing early angiogenesis.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2022-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46433878","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-27DOI: 10.1088/1748-605X/ac6b03
R. Hang, Xue Tian, Guangping Qu, Yuyu Zhao, Runhua Yao, Yi Zhang, Wenfa Wei, Xiaohong Yao, P. K. Chu
Angiogenesis, an essential prerequisite to osteogenesis in bone repair and regeneration, can be mediated by immunoregulation of macrophages. Magnesium and its alloys are promising biodegradable bone implant materials and can affect immunoregulation of macrophages by the degradation products (magnesium ions). Nevertheless, the mechanism of macrophage-derived exosomes stimulated by Mg ions in immunoregulation is still not well understood. Herein, 10–50 mM magnesium ions are shown to inhibit the macrophage viability and proliferation in a dose-dependent manner, but a high concentration results in macrophage apoptosis. The exosomes secreted by macrophages from magnesium ion stimulation inhibit angiogenesis of endothelial cells, as manifested by the suppressed cell viability, proliferation, migration, and tube formation, which arise at least partially from exosome-mediated downregulation of endothelial nitric oxide and the vascular endothelial growth factor. The findings reported in this paper suggest that the bio-functionality of biodegradable magnesium alloys must be considered from the perspective of immunoregulation of macrophage-derived exosomes. Our results also suggest potential cancer therapy by inhibiting tumor-associated angiogenesis.
{"title":"Exosomes derived from magnesium ion—stimulated macrophages inhibit angiogenesis","authors":"R. Hang, Xue Tian, Guangping Qu, Yuyu Zhao, Runhua Yao, Yi Zhang, Wenfa Wei, Xiaohong Yao, P. K. Chu","doi":"10.1088/1748-605X/ac6b03","DOIUrl":"https://doi.org/10.1088/1748-605X/ac6b03","url":null,"abstract":"Angiogenesis, an essential prerequisite to osteogenesis in bone repair and regeneration, can be mediated by immunoregulation of macrophages. Magnesium and its alloys are promising biodegradable bone implant materials and can affect immunoregulation of macrophages by the degradation products (magnesium ions). Nevertheless, the mechanism of macrophage-derived exosomes stimulated by Mg ions in immunoregulation is still not well understood. Herein, 10–50 mM magnesium ions are shown to inhibit the macrophage viability and proliferation in a dose-dependent manner, but a high concentration results in macrophage apoptosis. The exosomes secreted by macrophages from magnesium ion stimulation inhibit angiogenesis of endothelial cells, as manifested by the suppressed cell viability, proliferation, migration, and tube formation, which arise at least partially from exosome-mediated downregulation of endothelial nitric oxide and the vascular endothelial growth factor. The findings reported in this paper suggest that the bio-functionality of biodegradable magnesium alloys must be considered from the perspective of immunoregulation of macrophage-derived exosomes. Our results also suggest potential cancer therapy by inhibiting tumor-associated angiogenesis.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2022-04-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46230204","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-21DOI: 10.1088/1748-605X/ac6922
Sonu Singh, Priya Vashisth, V. Meena, D. Kalyanasundaram
Site-specific drug delivery has the potential to reduce drug dosage by 3- to 5-folds. Given the propensity of drugs used in the treatment of tuberculosis and cancers, the increased drug dosages via oral ingestion for several months to a few years of medication is often detrimental to the health of patients. In this study, the sustained delivery of drugs with multiscale structured novel Neovius lattices was achieved. 3D Neovius open cell lattices (NOCL) with porosities of 40%, 45%, and 50% were fabricated layer-by-layer on the laser bed fusion process. Micron-sized Ti6Al4V ELI powder was used for 3D printing. The Young’s modulus achieved from the novel Neovius lattices were in the range of 1.2–1.6 GPa, which is comparable to human cortical bone and helps to improve implant failure due to the stress shielding effect. To provide sustained drug delivery, nanotubes (NTs) were fabricated on NOCLs via high-voltage anodization. The osteogenic agent icariin was loaded onto the NOCL-NT samples and their release profiles were studied for 7 d. A significantly steady and slow release rate of 0.05% per hour of the drug was achieved using NOCL-NT. In addition, the initial burst release of NOCL-NT was 4 fold lower than that of the open-cell lattices without NTs. Cellular studies using MG63 human osteoblast-like cells were performed to determine their biocompatibility and osteogenesis which were analyzed using Calcein AM staining and Alamar Blue after 1, 5, and 7 d. 3D printed NOCL samples with NTs and with Icariin loaded NTs demonstrated a significant increase in cell proliferation as compared to as printed NOCL samples.
{"title":"Cellular studies and sustained drug delivery via nanostructures fabricated on 3D printed porous Neovius lattices of Ti6Al4V ELI","authors":"Sonu Singh, Priya Vashisth, V. Meena, D. Kalyanasundaram","doi":"10.1088/1748-605X/ac6922","DOIUrl":"https://doi.org/10.1088/1748-605X/ac6922","url":null,"abstract":"Site-specific drug delivery has the potential to reduce drug dosage by 3- to 5-folds. Given the propensity of drugs used in the treatment of tuberculosis and cancers, the increased drug dosages via oral ingestion for several months to a few years of medication is often detrimental to the health of patients. In this study, the sustained delivery of drugs with multiscale structured novel Neovius lattices was achieved. 3D Neovius open cell lattices (NOCL) with porosities of 40%, 45%, and 50% were fabricated layer-by-layer on the laser bed fusion process. Micron-sized Ti6Al4V ELI powder was used for 3D printing. The Young’s modulus achieved from the novel Neovius lattices were in the range of 1.2–1.6 GPa, which is comparable to human cortical bone and helps to improve implant failure due to the stress shielding effect. To provide sustained drug delivery, nanotubes (NTs) were fabricated on NOCLs via high-voltage anodization. The osteogenic agent icariin was loaded onto the NOCL-NT samples and their release profiles were studied for 7 d. A significantly steady and slow release rate of 0.05% per hour of the drug was achieved using NOCL-NT. In addition, the initial burst release of NOCL-NT was 4 fold lower than that of the open-cell lattices without NTs. Cellular studies using MG63 human osteoblast-like cells were performed to determine their biocompatibility and osteogenesis which were analyzed using Calcein AM staining and Alamar Blue after 1, 5, and 7 d. 3D printed NOCL samples with NTs and with Icariin loaded NTs demonstrated a significant increase in cell proliferation as compared to as printed NOCL samples.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2022-04-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45778311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-20DOI: 10.1088/1748-605X/ac68bc
Sen Yang, Hua Jiang, Meng Qian, Guangbo Ji, Yongzhen Wei, Ju He, H. Tian, Qiang Zhao
Designing hydrogel-based constructs capable of adjusting immune cell functions holds promise for skin tissue regeneration. Mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) have attracted increasing attention owing to their anti-inflammatory and proangiogenic effects. Herein, we constructed a biofunctional hydrogel in which MSC-derived sEVs were incorporated into the injectable hyaluronic acid hydrogel, thus endowing the hydrogel with immunomodulatory effects. When implanted onto the wound site in a mouse large skin injury model, this functional hydrogel facilitates wound healing and inhibits scar tissue formation by driving macrophages towards an anti-inflammatory and anti-fibrotic (M2c) phenotype. Further investigation showed that the M2c-like phenotype induced by MSC-derived sEVs markedly inhibited the activation of fibroblasts, which could result in scarless skin wound healing. Taken together, these results suggest that modulation of the immune response is a promising and efficient approach to prevent fibrotic scar formation.
{"title":"MSC-derived sEV-loaded hyaluronan hydrogel promotes scarless skin healing by immunomodulation in a large skin wound model","authors":"Sen Yang, Hua Jiang, Meng Qian, Guangbo Ji, Yongzhen Wei, Ju He, H. Tian, Qiang Zhao","doi":"10.1088/1748-605X/ac68bc","DOIUrl":"https://doi.org/10.1088/1748-605X/ac68bc","url":null,"abstract":"Designing hydrogel-based constructs capable of adjusting immune cell functions holds promise for skin tissue regeneration. Mesenchymal stem cell (MSC)-derived small extracellular vesicles (sEVs) have attracted increasing attention owing to their anti-inflammatory and proangiogenic effects. Herein, we constructed a biofunctional hydrogel in which MSC-derived sEVs were incorporated into the injectable hyaluronic acid hydrogel, thus endowing the hydrogel with immunomodulatory effects. When implanted onto the wound site in a mouse large skin injury model, this functional hydrogel facilitates wound healing and inhibits scar tissue formation by driving macrophages towards an anti-inflammatory and anti-fibrotic (M2c) phenotype. Further investigation showed that the M2c-like phenotype induced by MSC-derived sEVs markedly inhibited the activation of fibroblasts, which could result in scarless skin wound healing. Taken together, these results suggest that modulation of the immune response is a promising and efficient approach to prevent fibrotic scar formation.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2022-04-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"44849524","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-12DOI: 10.1088/1748-605X/ac66b2
P. Michael, Nianji Yang, M. Moore, Miguel Santos, Y. Lam, Annabelle Ward, J. Hung, R. Tan, S. Wise
Access to lab-grown fully functional blood vessels would provide an invaluable resource to vascular medicine. The complex architecture and cellular makeup of native vessels, however, makes this extremely challenging to reproduce in vitro. Bioreactor systems have helped advanced research in this area by replicating many of the physiological conditions necessary for full-scale tissue growth outside of the body. A key element underpinning these technologies are 3D vascular graft templates which serve as temporary scaffolds to direct cell growth into similar cellular architectures observed in native vessels. Grafts further engineered with appropriate physical cues to accommodate the multiple cell types that reside within native vessels may help improve the production efficiency and physiological accuracy of bioreactor-grown vessel substitutes. Here, we engineered two distinct scaffold architectures into an electrospun vascular graft aiming to encourage the spatial organisation of human vascular endothelial cells (hCAECs) in a continuous luminal monolayer, co-cultured with human fibroblasts (hFBs) populating the graft wall. Using an electrospun composite of polycaprolactone and gelatin, we evaluated physical parameters including fibre diameter, fibre alignment, and porosity, that best mimicked the spatial composition and growth of hCAECs and hFBs in native vessels. Upon identifying the optimal scaffold architectures for each cell type, we constructed a custom-designed mandrel that combined these distinct architectures into a single vascular graft during a single electrospinning processing run. When connected to a perfusion bioreactor system, the dual architecture graft spatially oriented hCAECs and hFBs into the graft wall and lumen, respectively, directly from circulation. This biomimetic cell organisation was consistent with positive graft remodelling with significant collagen deposition in the graft wall. These findings demonstrate the influence of architectural cues to direct cell growth within vascular graft templates and the future potential of these approaches to more accurately and efficiency produce blood vessel substitutes in bioreactor systems.
{"title":"Synthetic vascular graft with spatially distinct architecture for rapid biomimetic cell organisation in a perfusion bioreactor","authors":"P. Michael, Nianji Yang, M. Moore, Miguel Santos, Y. Lam, Annabelle Ward, J. Hung, R. Tan, S. Wise","doi":"10.1088/1748-605X/ac66b2","DOIUrl":"https://doi.org/10.1088/1748-605X/ac66b2","url":null,"abstract":"Access to lab-grown fully functional blood vessels would provide an invaluable resource to vascular medicine. The complex architecture and cellular makeup of native vessels, however, makes this extremely challenging to reproduce in vitro. Bioreactor systems have helped advanced research in this area by replicating many of the physiological conditions necessary for full-scale tissue growth outside of the body. A key element underpinning these technologies are 3D vascular graft templates which serve as temporary scaffolds to direct cell growth into similar cellular architectures observed in native vessels. Grafts further engineered with appropriate physical cues to accommodate the multiple cell types that reside within native vessels may help improve the production efficiency and physiological accuracy of bioreactor-grown vessel substitutes. Here, we engineered two distinct scaffold architectures into an electrospun vascular graft aiming to encourage the spatial organisation of human vascular endothelial cells (hCAECs) in a continuous luminal monolayer, co-cultured with human fibroblasts (hFBs) populating the graft wall. Using an electrospun composite of polycaprolactone and gelatin, we evaluated physical parameters including fibre diameter, fibre alignment, and porosity, that best mimicked the spatial composition and growth of hCAECs and hFBs in native vessels. Upon identifying the optimal scaffold architectures for each cell type, we constructed a custom-designed mandrel that combined these distinct architectures into a single vascular graft during a single electrospinning processing run. When connected to a perfusion bioreactor system, the dual architecture graft spatially oriented hCAECs and hFBs into the graft wall and lumen, respectively, directly from circulation. This biomimetic cell organisation was consistent with positive graft remodelling with significant collagen deposition in the graft wall. These findings demonstrate the influence of architectural cues to direct cell growth within vascular graft templates and the future potential of these approaches to more accurately and efficiency produce blood vessel substitutes in bioreactor systems.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2022-04-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43935590","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-08DOI: 10.1088/1748-605X/ac65cd
Junfeng Chen, Guangxiu Cao, Linhao Li, Q. Cai, N. Dunne, Xiaoming Li
Bone damage as a consequence of disease or trauma is a common global occurrence. For bone damage treatment—bone implant materials are necessary across three classifications of surgical intervention (i.e. fixation, repair, and replacement). Many types of bone implant materials have been developed to meet the requirements of bone repair. Among them, polyether ether ketone (PEEK) has been considered as one of the next generation of bone implant materials, owing to its advantages related to good biocompatibility, chemical stability, x-ray permeability, elastic modulus comparable to natural bone, as well as the ease of processing and modification. However, as PEEK is a naturally bioinert material, some modification is needed to improve its integration with adjacent bones after implantation. Therefore, it has become a very hot topic of biomaterials research and various strategies for the modification of PEEK including blending, 3D printing, coating, chemical modification and the introduction of bioactive and/or antibacterial substances have been proposed. In this systematic review, the recent advances in modification of PEEK and its application prospect as bone implants are summarized, and the remaining challenges are also discussed.
{"title":"Modification of polyether ether ketone for the repairing of bone defects","authors":"Junfeng Chen, Guangxiu Cao, Linhao Li, Q. Cai, N. Dunne, Xiaoming Li","doi":"10.1088/1748-605X/ac65cd","DOIUrl":"https://doi.org/10.1088/1748-605X/ac65cd","url":null,"abstract":"Bone damage as a consequence of disease or trauma is a common global occurrence. For bone damage treatment—bone implant materials are necessary across three classifications of surgical intervention (i.e. fixation, repair, and replacement). Many types of bone implant materials have been developed to meet the requirements of bone repair. Among them, polyether ether ketone (PEEK) has been considered as one of the next generation of bone implant materials, owing to its advantages related to good biocompatibility, chemical stability, x-ray permeability, elastic modulus comparable to natural bone, as well as the ease of processing and modification. However, as PEEK is a naturally bioinert material, some modification is needed to improve its integration with adjacent bones after implantation. Therefore, it has become a very hot topic of biomaterials research and various strategies for the modification of PEEK including blending, 3D printing, coating, chemical modification and the introduction of bioactive and/or antibacterial substances have been proposed. In this systematic review, the recent advances in modification of PEEK and its application prospect as bone implants are summarized, and the remaining challenges are also discussed.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2022-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"43885724","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-08DOI: 10.1088/1748-605X/ac65cc
Tingting Wu, Binglin Li, Wen‐chan Huang, Xianli Zeng, Yiwan Shi, Zefeng Lin, Chengxiong Lin, Weikang Xu, Hong Xia, Tao Zhang
Recently, biofunctional ions (Mg2+, Si4+, etc) and graphene derivatives are proved to be promising in stimulating bone formation. In this study, a novel inorganic/organic composite porous scaffold based on silk fibroin (SF), graphene oxide (GO), and calcium magnesium silicate (CMS) was developed for bone repair. The porous scaffolds obtained by lyophilization showed a little difference in pore structure while GO and CMS displayed a good interaction with SF matrix. The addition of CMS with good mineralization potential and sustainedly release ability of biofunctional ions (Ca2+, Mg2+ and Si4+) increased the strength of SF scaffolds a little and facilitated the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) by upregulating bone formation-related genes (ALP, COL1, OC and Runx2). The further incorporation of GO in SF scaffolds enhanced the compressive strength and water retention, and also remarkably promoted the osteogenic differentiation of BMSCs. Besides, the angiogenesis of human umbilical vein endothelial cells was significantly promoted by CMS/GO/SF scaffold extract through the upregulation of angiogenesis genes (eNOs and bFGF). Moreover, the osteoclastic formation ability of RAW264.7 cells was suppressed by the released ions from CMS/GO/SF scaffold through the down-regulation of CAK, MMP9 and TRAP. The promoted osteogenesis, angiogenesis and inhibited osteoclastogenesis functions of CMS/GO/SF composite scaffold may enable it as a novel therapy for bone repair and regeneration.
{"title":"Developing a novel calcium magnesium silicate/graphene oxide incorporated silk fibroin porous scaffold with enhanced osteogenesis, angiogenesis and inhibited osteoclastogenesis","authors":"Tingting Wu, Binglin Li, Wen‐chan Huang, Xianli Zeng, Yiwan Shi, Zefeng Lin, Chengxiong Lin, Weikang Xu, Hong Xia, Tao Zhang","doi":"10.1088/1748-605X/ac65cc","DOIUrl":"https://doi.org/10.1088/1748-605X/ac65cc","url":null,"abstract":"Recently, biofunctional ions (Mg2+, Si4+, etc) and graphene derivatives are proved to be promising in stimulating bone formation. In this study, a novel inorganic/organic composite porous scaffold based on silk fibroin (SF), graphene oxide (GO), and calcium magnesium silicate (CMS) was developed for bone repair. The porous scaffolds obtained by lyophilization showed a little difference in pore structure while GO and CMS displayed a good interaction with SF matrix. The addition of CMS with good mineralization potential and sustainedly release ability of biofunctional ions (Ca2+, Mg2+ and Si4+) increased the strength of SF scaffolds a little and facilitated the osteogenic differentiation of bone mesenchymal stem cells (BMSCs) by upregulating bone formation-related genes (ALP, COL1, OC and Runx2). The further incorporation of GO in SF scaffolds enhanced the compressive strength and water retention, and also remarkably promoted the osteogenic differentiation of BMSCs. Besides, the angiogenesis of human umbilical vein endothelial cells was significantly promoted by CMS/GO/SF scaffold extract through the upregulation of angiogenesis genes (eNOs and bFGF). Moreover, the osteoclastic formation ability of RAW264.7 cells was suppressed by the released ions from CMS/GO/SF scaffold through the down-regulation of CAK, MMP9 and TRAP. The promoted osteogenesis, angiogenesis and inhibited osteoclastogenesis functions of CMS/GO/SF composite scaffold may enable it as a novel therapy for bone repair and regeneration.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2022-04-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"46100394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2022-04-05DOI: 10.1088/1748-605X/ac6471
Juhi Chakraborty, Subhadeep Roy, Sourabh Ghosh
3D porous hydroxyapatite (HAP) scaffolds produced by conventional foaming processes have limited control over the scaffold’s pore size, geometry, and pore interconnectivity. In addition, random internal pore architecture often results in limited clinical success. Imitating the intricate 3D architecture and the functional dynamics of skeletal deformations is a difficult task, highlighting the necessity for a custom-made, on-demand tissue replacement, for which 3D printing is a potential solution. To combat these problems, here we report the ability of 3D printed HAP scaffolds for in vivo bone regeneration in a rat tibial defect model. Rapid prototyping using the direct-write technique to fabricate 25 mm2 HAP scaffolds were employed for precise control over geometry (both external and internal) and scaffold chemistry. Bone ingrowth was determined using histomorphometry and a novel micro-computed tomography (micro-CT) image analysis. Substantial bone ingrowth was observed in implants that filled the defect site. Further validating this quantitatively by micro-CT, the Bone mineral density (BMD) of the implant at the defect site was 1024 mgHA ccm−1, which was approximately 61.5% more than the BMD found with the sham control at the defect site. In addition, no evident immunoinflammatory response was observed in the hematoxylin and eosin micrographs. Interestingly, the present study showed a positive correlation with the outcomes obtained in our previous in vitro study. Overall, the results suggest that 3D printed HAP scaffolds developed in this study offer a suitable matrix for rendering patient-specific and defect-specific bone formation and warrant further testing for clinical application.
{"title":"3D printed hydroxyapatite promotes congruent bone ingrowth in rat load bearing defects","authors":"Juhi Chakraborty, Subhadeep Roy, Sourabh Ghosh","doi":"10.1088/1748-605X/ac6471","DOIUrl":"https://doi.org/10.1088/1748-605X/ac6471","url":null,"abstract":"3D porous hydroxyapatite (HAP) scaffolds produced by conventional foaming processes have limited control over the scaffold’s pore size, geometry, and pore interconnectivity. In addition, random internal pore architecture often results in limited clinical success. Imitating the intricate 3D architecture and the functional dynamics of skeletal deformations is a difficult task, highlighting the necessity for a custom-made, on-demand tissue replacement, for which 3D printing is a potential solution. To combat these problems, here we report the ability of 3D printed HAP scaffolds for in vivo bone regeneration in a rat tibial defect model. Rapid prototyping using the direct-write technique to fabricate 25 mm2 HAP scaffolds were employed for precise control over geometry (both external and internal) and scaffold chemistry. Bone ingrowth was determined using histomorphometry and a novel micro-computed tomography (micro-CT) image analysis. Substantial bone ingrowth was observed in implants that filled the defect site. Further validating this quantitatively by micro-CT, the Bone mineral density (BMD) of the implant at the defect site was 1024 mgHA ccm−1, which was approximately 61.5% more than the BMD found with the sham control at the defect site. In addition, no evident immunoinflammatory response was observed in the hematoxylin and eosin micrographs. Interestingly, the present study showed a positive correlation with the outcomes obtained in our previous in vitro study. Overall, the results suggest that 3D printed HAP scaffolds developed in this study offer a suitable matrix for rendering patient-specific and defect-specific bone formation and warrant further testing for clinical application.","PeriodicalId":9016,"journal":{"name":"Biomedical materials","volume":" ","pages":""},"PeriodicalIF":4.0,"publicationDate":"2022-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"45478431","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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