Negin Khoshnood, John P. Frampton, Armin Badri, Ali Zamanian
Transparent hydrogels have numerous applications in materials science and tissue engineering, particularly as materials for corneal repair. In this study, we developed a three-dimensional (3D)-bioprinted betamethasone sodium phosphate-loaded gellan gum (GG)–polyethyleneimine (PEI) composite hydrogel and assessed its performance in vitro. The bioinks used for 3D bioprinting were optimized based on their transparency and gelation properties. In the presence of an ionic crosslinker (citric acid), the GG–PEI blend transformed from a liquid precursor to an extrudable hydrogel with good printability and shape fidelity. The 2.5% GG–3% PEI hydrogel formulation had a transparency of 80%, a suitable degradation rate, and sufficient mechanical strength for application in corneal repair. The GG–PEI composite hydrogel displayed controlled and sustained release of betamethasone sodium phosphate. Moreover, the 3D-bioprinted composite hydrogel was biocompatible, as evidenced by the attachment, growth, and proliferation of corneal fibroblasts. Taken together, these findings suggest that the 3D-bioprinted GG–PEI composite hydrogel scaffold has the potential to control ocular inflammation and aid in corneal tissue healing.
{"title":"3D bioprinting of betamethasone-loaded gellan gum–polyethyleneimine composite hydrogels for ocular drug delivery","authors":"Negin Khoshnood, John P. Frampton, Armin Badri, Ali Zamanian","doi":"10.36922/ijb.3440","DOIUrl":"https://doi.org/10.36922/ijb.3440","url":null,"abstract":"Transparent hydrogels have numerous applications in materials science and tissue engineering, particularly as materials for corneal repair. In this study, we developed a three-dimensional (3D)-bioprinted betamethasone sodium phosphate-loaded gellan gum (GG)–polyethyleneimine (PEI) composite hydrogel and assessed its performance in vitro. The bioinks used for 3D bioprinting were optimized based on their transparency and gelation properties. In the presence of an ionic crosslinker (citric acid), the GG–PEI blend transformed from a liquid precursor to an extrudable hydrogel with good printability and shape fidelity. The 2.5% GG–3% PEI hydrogel formulation had a transparency of 80%, a suitable degradation rate, and sufficient mechanical strength for application in corneal repair. The GG–PEI composite hydrogel displayed controlled and sustained release of betamethasone sodium phosphate. Moreover, the 3D-bioprinted composite hydrogel was biocompatible, as evidenced by the attachment, growth, and proliferation of corneal fibroblasts. Taken together, these findings suggest that the 3D-bioprinted GG–PEI composite hydrogel scaffold has the potential to control ocular inflammation and aid in corneal tissue healing.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-07-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141831378","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}
Embedded bioprinting enables direct deposition of bioinks in three dimensions inside a support bath with shear-thinning and self-healing capabilities, and it has been used to fabricate complex tissues and organs for several biomedical applications. In this study, a support bath comprising gelatin/alginate microparticles and oxidized alginate solution was developed and crosslinked in situ with carbonyl hydrazide-modified gelatin bioink via the Schiff base reaction. The numerical model of embedded printing was established to analyze the extrusion process and disturbance of the support bath. The process window (e.g., extrusion pressure, nozzle moving speed, nozzle size, and support bath composition) was established experimentally to ensure stable fiber formation. In addition, the compressive modulus of the printed construct has been reinforced due to the formation of interpenetrating polymer networks in the microparticles. Based on the process investigation, a zonally stratified artificial cartilage with a three-layered structure was designed: vertically printed fibers in the bottom, oblique fibers in the middle, and horizontally printed fibers in the superficial layer. The bioprinted cartilage supported cell survival, proliferation, and spreading, with the observed deposition of cartilage-specific proteins, offering a new strategy for developing tissue-engineered cartilage constructs with biological and histological relevance.
{"title":"Development of embedded bioprinting for fabricating zonally stratified articular cartilage","authors":"Yang Wu, Xue Yang, Tianying Yuan, Seung Yeon Lee, Minghao Qin, Sung Jun Min, Bingxian Lu, Pengkun Guo, Jiarui Xie, Shengli Mi, Dong Nyoung Heo","doi":"10.36922/ijb.3520","DOIUrl":"https://doi.org/10.36922/ijb.3520","url":null,"abstract":"Embedded bioprinting enables direct deposition of bioinks in three dimensions inside a support bath with shear-thinning and self-healing capabilities, and it has been used to fabricate complex tissues and organs for several biomedical applications. In this study, a support bath comprising gelatin/alginate microparticles and oxidized alginate solution was developed and crosslinked in situ with carbonyl hydrazide-modified gelatin bioink via the Schiff base reaction. The numerical model of embedded printing was established to analyze the extrusion process and disturbance of the support bath. The process window (e.g., extrusion pressure, nozzle moving speed, nozzle size, and support bath composition) was established experimentally to ensure stable fiber formation. In addition, the compressive modulus of the printed construct has been reinforced due to the formation of interpenetrating polymer networks in the microparticles. Based on the process investigation, a zonally stratified artificial cartilage with a three-layered structure was designed: vertically printed fibers in the bottom, oblique fibers in the middle, and horizontally printed fibers in the superficial layer. The bioprinted cartilage supported cell survival, proliferation, and spreading, with the observed deposition of cartilage-specific proteins, offering a new strategy for developing tissue-engineered cartilage constructs with biological and histological relevance.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141648922","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}
D. Martínez‐Moreno, A. Callejas, Gema Jiménez, P. Gálvez-Martín, Guillermo Rus, Juan Antonio Marchal
Osteoarthritis is a significant socioeconomic illness that mainly affects the articular cartilage, a tissue with a low capacity for self-healing, making it an ideal target for regenerative medicine and tissue engineering. Current interventions to treat cartilage injuries may not be completely effective. In this study, we have developed a novel bioreactor that creates viscous shear stress by flow perfusion. This bioreactor could induce ex vivo maturation of biomimetic 3D cartilage scaffolds, providing a potential solution to this problem. Infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs) were used as a cellular source of the functionalized 3D scaffolds made of 1,4-butanediol thermoplastic polyurethane (bTPUe) modified with pyrene butyric acid (PBA). Our results indicate that our bioreactor induced chondrogenic differentiation, as confirmed by DNA quantification, extracellular matrix determination, and metabolic assay, without any conditioned medium. To control the biomechanical stimulation on IPFP-MSCs, a low-intensity ultrasonic transmission system has been developed and embedded in the bioreactor. Combined with a finite element model (FEM), tissue growth and differentiation can be deconvoluted in real-time from the recorded ultrasonic propagation and interaction across the graft. The FEM reconstructs this complex interaction. This is the first time a low-shear stress-based bioreactor has been reported to not only induce chondrogenic evolution but also monitor it in real time.
{"title":" Induction and real-time ultrasonic monitoring of 3D cartilage-like tissue by a low shear stresses-based bioreactor","authors":"D. Martínez‐Moreno, A. Callejas, Gema Jiménez, P. Gálvez-Martín, Guillermo Rus, Juan Antonio Marchal","doi":"10.36922/ijb.3389","DOIUrl":"https://doi.org/10.36922/ijb.3389","url":null,"abstract":"Osteoarthritis is a significant socioeconomic illness that mainly affects the articular cartilage, a tissue with a low capacity for self-healing, making it an ideal target for regenerative medicine and tissue engineering. Current interventions to treat cartilage injuries may not be completely effective. In this study, we have developed a novel bioreactor that creates viscous shear stress by flow perfusion. This bioreactor could induce ex vivo maturation of biomimetic 3D cartilage scaffolds, providing a potential solution to this problem. Infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs) were used as a cellular source of the functionalized 3D scaffolds made of 1,4-butanediol thermoplastic polyurethane (bTPUe) modified with pyrene butyric acid (PBA). Our results indicate that our bioreactor induced chondrogenic differentiation, as confirmed by DNA quantification, extracellular matrix determination, and metabolic assay, without any conditioned medium. To control the biomechanical stimulation on IPFP-MSCs, a low-intensity ultrasonic transmission system has been developed and embedded in the bioreactor. Combined with a finite element model (FEM), tissue growth and differentiation can be deconvoluted in real-time from the recorded ultrasonic propagation and interaction across the graft. The FEM reconstructs this complex interaction. This is the first time a low-shear stress-based bioreactor has been reported to not only induce chondrogenic evolution but also monitor it in real time.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141652740","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}
Enric Casanova-Batlle, Maria Ros, Emma Polonio-Alcalá, Sira Ausellé-Bosch, Teresa Puig, A. Guerra, Joaquim Ciurana
Bioresorbable stents (BRS) are manufactured using biodegradable materials. As an alternative to those commonly used in commercial stents, this study explored the development of BRS using polyvinyl alcohol (PVA) and silk fibroin (SF). PVA is a promising material for the fabrication of BRS due to its biocompatibility and mechanical attributes, closely resembling those of aortic vessels. However, its application presents challenges in terms of cell adhesion and proliferation. SF has been extensively studied for its potential to enhance cell adhesion and proliferation, making it a promising biomaterial in the field of medical devices. SF was introduced by dissolving it in a PVA solution or by coating the hydrogel surface with a layer of SF. Initial tests revealed that overnight incubation of fetal bovine serum significantly increased cell viability in hydrogels. Viability assays confirmed that SF substantially improved cell viability compared to PVA alone. The method was extended to fabricate SF-coated stents, which demonstrated robust cell proliferation and improved performance compared to electrospun polycaprolactone scaffolds. In addition, the SF-coated stents displayed an increase in compressive strength, demonstrating improved biocompatibility and mechanical performance. Dynamic mechanical analysis evaluated the positive impact of SF on stent properties at physiological temperatures. The study revealed that PVA-SF stents offer a compromise between biocompatibility, mechanical strength, and elastic recovery, positioning them as a valuable alternative for cardiovascular stent applications. The dual benefits of enhanced biocompatibility and improved mechanical performance make SF-coated stents promising candidates for bioresorbable stent design.
生物可吸收支架（BRS）是使用生物可降解材料制造的。作为商用支架常用材料的替代品，本研究探讨了使用聚乙烯醇（PVA）和丝纤维素（SF）开发生物可吸收支架的问题。聚乙烯醇具有生物相容性和机械属性，与主动脉血管的机械属性非常相似，因此是一种很有希望用于制造 BRS 的材料。然而，其应用在细胞粘附和增殖方面存在挑战。SF 因其增强细胞粘附和增殖的潜力而被广泛研究，使其成为医疗器械领域一种前景广阔的生物材料。通过在 PVA 溶液中溶解 SF 或在水凝胶表面涂上一层 SF，引入了 SF。初步测试表明，胎牛血清过夜培养可显著提高水凝胶中的细胞活力。活力测定证实，与单独使用 PVA 相比，SF 大大提高了细胞活力。该方法被扩展用于制造 SF 涂层支架，与电纺聚己内酯支架相比，SF 涂层支架具有更强的细胞增殖能力和更好的性能。此外，SF 涂层支架的抗压强度也有所提高，这表明生物相容性和机械性能得到了改善。动态力学分析评估了 SF 在生理温度下对支架性能的积极影响。研究结果表明，PVA-SF 支架在生物相容性、机械强度和弹性恢复之间实现了折中，可作为心血管支架应用的重要替代品。增强生物相容性和改善机械性能的双重优势使 SF 涂层支架有望成为生物可吸收支架设计的候选材料。
{"title":"Polyvinyl alcohol-silk fibroin composite stents: A comprehensive investigation into biocompatibility and mechanical performance","authors":"Enric Casanova-Batlle, Maria Ros, Emma Polonio-Alcalá, Sira Ausellé-Bosch, Teresa Puig, A. Guerra, Joaquim Ciurana","doi":"10.36922/ijb.3444","DOIUrl":"https://doi.org/10.36922/ijb.3444","url":null,"abstract":"Bioresorbable stents (BRS) are manufactured using biodegradable materials. As an alternative to those commonly used in commercial stents, this study explored the development of BRS using polyvinyl alcohol (PVA) and silk fibroin (SF). PVA is a promising material for the fabrication of BRS due to its biocompatibility and mechanical attributes, closely resembling those of aortic vessels. However, its application presents challenges in terms of cell adhesion and proliferation. SF has been extensively studied for its potential to enhance cell adhesion and proliferation, making it a promising biomaterial in the field of medical devices. SF was introduced by dissolving it in a PVA solution or by coating the hydrogel surface with a layer of SF. Initial tests revealed that overnight incubation of fetal bovine serum significantly increased cell viability in hydrogels. Viability assays confirmed that SF substantially improved cell viability compared to PVA alone. The method was extended to fabricate SF-coated stents, which demonstrated robust cell proliferation and improved performance compared to electrospun polycaprolactone scaffolds. In addition, the SF-coated stents displayed an increase in compressive strength, demonstrating improved biocompatibility and mechanical performance. Dynamic mechanical analysis evaluated the positive impact of SF on stent properties at physiological temperatures. The study revealed that PVA-SF stents offer a compromise between biocompatibility, mechanical strength, and elastic recovery, positioning them as a valuable alternative for cardiovascular stent applications. The dual benefits of enhanced biocompatibility and improved mechanical performance make SF-coated stents promising candidates for bioresorbable stent design. ","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141659712","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}
Nur Izzah Md Fadilah, Nur Aifa Asyhira Khairul Nizam, M. B. Fauzi
Wounds represent a critical issue in the healthcare industry since they are highly susceptible to infections that in turn lead to more serious complications. With bacterial infections gradually growing to be a challenge to wound healing, fighting bacterial resistance has become one of the important pillars of addressing issues faced by healthcare personnel. Thus, gaining an understanding of the distinct stages of wound healing is vital to further improve relevant therapies incorporating the application of antibacterial compounds. Recently, three-dimensional (3D)-printed functional biomaterials have emerged as an alternative treatment or potential carriers incorporating relevant antibacterial agents, offering a new approach to skin tissue engineering. Novel strategies for skin tissue engineering are grounded in the integration of bioactive ingredients and antibacterial agents into biomaterials with different morphologies to improve cell behaviors and promote wound healing by preventing bacterial colonization. This paper reviews the function of natural and synthetic polymers, effects of antibacterial properties, and cell interactions in terms of the wound healing process. Extensive research has demonstrated that 3D functional biomaterials exert their therapeutic effects through multifaceted pathways, including but not limited to, modulating inflammation, facilitating tissue regeneration, promoting cell proliferation, enhancing angiogenesis, and controlling infection. This review also provides general insights into the elegant design for 3D scaffold and further refinement of wound dressing.
{"title":"Antibacterial compounds-incorporated functional biomaterials for chronic wound healing application via 3D bioprinting: The mechanism of action","authors":"Nur Izzah Md Fadilah, Nur Aifa Asyhira Khairul Nizam, M. B. Fauzi","doi":"10.36922/ijb.3372","DOIUrl":"https://doi.org/10.36922/ijb.3372","url":null,"abstract":"Wounds represent a critical issue in the healthcare industry since they are highly susceptible to infections that in turn lead to more serious complications. With bacterial infections gradually growing to be a challenge to wound healing, fighting bacterial resistance has become one of the important pillars of addressing issues faced by healthcare personnel. Thus, gaining an understanding of the distinct stages of wound healing is vital to further improve relevant therapies incorporating the application of antibacterial compounds. Recently, three-dimensional (3D)-printed functional biomaterials have emerged as an alternative treatment or potential carriers incorporating relevant antibacterial agents, offering a new approach to skin tissue engineering. Novel strategies for skin tissue engineering are grounded in the integration of bioactive ingredients and antibacterial agents into biomaterials with different morphologies to improve cell behaviors and promote wound healing by preventing bacterial colonization. This paper reviews the function of natural and synthetic polymers, effects of antibacterial properties, and cell interactions in terms of the wound healing process. Extensive research has demonstrated that 3D functional biomaterials exert their therapeutic effects through multifaceted pathways, including but not limited to, modulating inflammation, facilitating tissue regeneration, promoting cell proliferation, enhancing angiogenesis, and controlling infection. This review also provides general insights into the elegant design for 3D scaffold and further refinement of wound dressing.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141676985","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}
Yanyan Ding, Qin Liu, Jinwu Chen, Hua Cai, Yue Qiu, Ming Li, Le Xie, Zhenyu Zhao, Ying Xiao
Hearing loss is a prevalent worldwide health concern, characterized by structural or functional abnormalities in any part of the ear resulting in varying degrees of auditory dysfunction. Despite significant progress, there exists a notable deficiency in reliable and safe therapeutic interventions for addressing hearing loss. Bioprinting, a novel method in the realm of advanced tissue engineering, exhibits significant potential in addressing ear-related ailments. This technology provides a wide range of repair mechanisms specifically designed to address the distinct anatomical and functional requirements of the outer ear, middle ear, and inner ear, potentially leading to advancements in the treatment of different types of hearing loss. Furthermore, bioprinting holds promise for producing tissue constructs that are both anatomically accurate and functionally suitable, potentially revolutionizing the current treatment landscape. Nevertheless, thorough research and development efforts are necessary to fully harness the capabilities of bioprinting and establish it as a widely accepted treatment option for hearing loss.
{"title":"Advancements in bioprinting for the treatment of hearing loss: A review","authors":"Yanyan Ding, Qin Liu, Jinwu Chen, Hua Cai, Yue Qiu, Ming Li, Le Xie, Zhenyu Zhao, Ying Xiao","doi":"10.36922/ijb.3497","DOIUrl":"https://doi.org/10.36922/ijb.3497","url":null,"abstract":"Hearing loss is a prevalent worldwide health concern, characterized by structural or functional abnormalities in any part of the ear resulting in varying degrees of auditory dysfunction. Despite significant progress, there exists a notable deficiency in reliable and safe therapeutic interventions for addressing hearing loss. Bioprinting, a novel method in the realm of advanced tissue engineering, exhibits significant potential in addressing ear-related ailments. This technology provides a wide range of repair mechanisms specifically designed to address the distinct anatomical and functional requirements of the outer ear, middle ear, and inner ear, potentially leading to advancements in the treatment of different types of hearing loss. Furthermore, bioprinting holds promise for producing tissue constructs that are both anatomically accurate and functionally suitable, potentially revolutionizing the current treatment landscape. Nevertheless, thorough research and development efforts are necessary to fully harness the capabilities of bioprinting and establish it as a widely accepted treatment option for hearing loss.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-07-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141677194","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}
Angela Cirulli, Livia Neves Borgheti-Cardoso, Núria Torras, Elena Martinez
There has been a huge demand for engineered skin tissues in the realms of both in vitro and in vivo applications. Selecting the right material scaffold is a critical consideration in making engineered skin tissues, since it should possess a good balance between elasticity and mechanical stability while promoting an adequate cell microenvironment to support both the dermal and the epidermal compartments of skin tissue. In this study, 3D-bioprinted norbornene-pullulan photocrosslinkable hydrogels were utilized as alternative scaffolds to produce epithelized dermal skin models. By employing visible light, 2.5 mm3 cell-laden hydrogels could be printed in 10 s. The thiol-ene photocrosslinking chemistry employed in this work enabled the formation of a well-defined extracellular matrix with orthogonal crosslinks, where encapsulated fibroblasts maintained high cellular viability rates. Through this method, an epidermal layer could be grown on top of the fibroblasts. The coexistence and interaction of human fibroblasts and keratinocytes were visualized by determining the expression of specific markers. This approach represents a promising starting point for the development of photocrosslinkable hydrogel-based human skin constructs by using thiol-ene norbornene chemistry, paving the way toward manufacture of complex in vitro models of human tissues.
{"title":"Mimicking human skin constructs using norbornene-pullulan-based hydrogels","authors":"Angela Cirulli, Livia Neves Borgheti-Cardoso, Núria Torras, Elena Martinez","doi":"10.36922/ijb.3395","DOIUrl":"https://doi.org/10.36922/ijb.3395","url":null,"abstract":"There has been a huge demand for engineered skin tissues in the realms of both in vitro and in vivo applications. Selecting the right material scaffold is a critical consideration in making engineered skin tissues, since it should possess a good balance between elasticity and mechanical stability while promoting an adequate cell microenvironment to support both the dermal and the epidermal compartments of skin tissue. In this study, 3D-bioprinted norbornene-pullulan photocrosslinkable hydrogels were utilized as alternative scaffolds to produce epithelized dermal skin models. By employing visible light, 2.5 mm3 cell-laden hydrogels could be printed in 10 s. The thiol-ene photocrosslinking chemistry employed in this work enabled the formation of a well-defined extracellular matrix with orthogonal crosslinks, where encapsulated fibroblasts maintained high cellular viability rates. Through this method, an epidermal layer could be grown on top of the fibroblasts. The coexistence and interaction of human fibroblasts and keratinocytes were visualized by determining the expression of specific markers. This approach represents a promising starting point for the development of photocrosslinkable hydrogel-based human skin constructs by using thiol-ene norbornene chemistry, paving the way toward manufacture of complex in vitro models of human tissues. ","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-07-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141682705","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}
Replicating the heterogeneous structure and promoting compartmentalized osteogenesis/chondrogenesis are critical considerations in designing scaffolds for osteochondral tissue regeneration. However, desirable osteochondral regeneration cannot be achieved mainly due to the absence of effective delivery strategies for growth factors (GFs) and the insufficiency of desirable organizational morphologies for seed cells. Herein, we developed a tri-phasic osteochondral scaffold consisting of bone morphogenetic protein-2 (BMP-2)-loaded subchondral layer, fibroblast growth factor-18 (FGF-18)-loaded cartilage layer, and an interface layer that acted as a barrier to reduce the mutual interference of GFs, via cryogenic 3D bioprinting. BMP-2 could exert osteogenic effects for 14 days, and FGF-18 could exert chondrogenic effects for 21 days, demonstrating the time-controlled release function of BMP-2 and FGF-18. By further seeding discrete rat bone marrow mesenchymal stem cells (rBMSCs) and rBMSC microspheres, respectively, onto the subchondral layer and cartilage layer, the engineered cell-laden osteochondral tissue was constructed. The spatiotemporal release of BMP-2 and FGF-18 in the subchondral layer and cartilage layer promoted the osteogenic differentiation of discrete rBMSCs and chondrogenic differentiation of rBMSC microspheres in the subchondral layer and cartilage layer, respectively. In summary, by seeding rBMSCs with varied organizational morphologies in 3D-printed osteochondral scaffolds with a spatiotemporally controlled strategy, engineered osteochondral tissue with compartmentalized osteogenic/chondrogenic differentiation potent can be formed, displaying a facile and promising way to achieve desirable osteochondral tissue regeneration.
{"title":"Spatiotemporal delivery of BMP-2 and FGF-18 in 3D-bioprinted tri-phasic osteochondral scaffolds enhanced compartmentalized osteogenic and chondrogenic differentiation of mesenchymal stem cells isolated from rats with varied organizational morphologies","authors":"Weiwei Su, Shiyu Li, Panjing Yin, Weihan Zheng, Ling Wang, Zhuosheng Lin, Ziyue Li, Zi Yan, Yaobin Wu, Chong Wang, Wenhua Huang","doi":"10.36922/ijb.3229","DOIUrl":"https://doi.org/10.36922/ijb.3229","url":null,"abstract":"Replicating the heterogeneous structure and promoting compartmentalized osteogenesis/chondrogenesis are critical considerations in designing scaffolds for osteochondral tissue regeneration. However, desirable osteochondral regeneration cannot be achieved mainly due to the absence of effective delivery strategies for growth factors (GFs) and the insufficiency of desirable organizational morphologies for seed cells. Herein, we developed a tri-phasic osteochondral scaffold consisting of bone morphogenetic protein-2 (BMP-2)-loaded subchondral layer, fibroblast growth factor-18 (FGF-18)-loaded cartilage layer, and an interface layer that acted as a barrier to reduce the mutual interference of GFs, via cryogenic 3D bioprinting. BMP-2 could exert osteogenic effects for 14 days, and FGF-18 could exert chondrogenic effects for 21 days, demonstrating the time-controlled release function of BMP-2 and FGF-18. By further seeding discrete rat bone marrow mesenchymal stem cells (rBMSCs) and rBMSC microspheres, respectively, onto the subchondral layer and cartilage layer, the engineered cell-laden osteochondral tissue was constructed. The spatiotemporal release of BMP-2 and FGF-18 in the subchondral layer and cartilage layer promoted the osteogenic differentiation of discrete rBMSCs and chondrogenic differentiation of rBMSC microspheres in the subchondral layer and cartilage layer, respectively. In summary, by seeding rBMSCs with varied organizational morphologies in 3D-printed osteochondral scaffolds with a spatiotemporally controlled strategy, engineered osteochondral tissue with compartmentalized osteogenic/chondrogenic differentiation potent can be formed, displaying a facile and promising way to achieve desirable osteochondral tissue regeneration.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141688331","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}
Tang Liu, Yuxin Lin, Lin Sang, Fei Wang, Jiawei Hu, Kun Guo, Shanglian Ju, Yiping Zhao, Xiaohong Shu
Bone bionics and structural engineering have played a vital role in bone regeneration, with artificial scaffolds generating widespread interest. However, the mechanical properties and bone regeneration potential of biomimetic structures remain unclear. Herein, biodegradable polymer composites based on poly(butylene adipate-co-terephthalate)/poly(lactic acid) (PBAT/PLA) were 3D-printed into lattice structures as tissue engineering scaffolds. For structural design, graded diamond (D) minimal surfaces were proposed and designed to mimic the natural bone structure. The graded topologies were realized by designing gradient thickness either radially from center to edge or vertically from top to bottom. The mechanical performance of these graded samples displayed better load-carrying and energy absorption capacity than the uniform counterparts. No obvious damage was detected in the internal microstructure of the compressed samples using computed tomography. Subsequently, platelet-rich plasma (PRP), containing diverse cytokines, was loaded on the graded scaffolds. The PRP-loaded D-scaffold reported improved in vitro cell proliferation and osteoblast differentiation. Finally, femoral condyle defect repair results indicated that the PRP-loaded D-scaffold effectively promoted early-stage bone regeneration. Overall, this work provides insights into fabricating artificial scaffolds with bioactive factors and biomimetic lattice structures.
骨仿生学和结构工程在骨再生方面发挥了重要作用，人工支架引起了广泛关注。然而，生物仿生结构的机械性能和骨再生潜力仍不明确。在本文中，基于聚（丁烯二酸酯-对苯二甲酸酯）/聚（乳酸）（PBAT/PLA）的生物可降解聚合物复合材料被三维打印成晶格结构，作为组织工程支架。在结构设计方面，提出并设计了分级钻石（D）最小表面，以模仿天然骨骼结构。通过设计从中心到边缘的径向梯度厚度或从顶部到底部的垂直梯度厚度，实现了梯度拓扑结构。这些分级样品的机械性能显示出比均匀样品更好的承载能力和能量吸收能力。通过计算机断层扫描，压缩样品的内部微观结构没有发现明显的损伤。随后，将含有多种细胞因子的富血小板血浆（PRP）加载到分级支架上。据报道，PRP 负载的 D 型支架改善了体外细胞增殖和成骨细胞分化。最后，股骨髁缺损修复结果表明，PRP 负载的 D 型支架能有效促进早期骨再生。总之，这项研究为制造含有生物活性因子和仿生晶格结构的人工支架提供了新的视角。
{"title":"Biomimetic structural design and performance study of 3D-printed graded minimal surface bone scaffolds with enhanced bioactivity","authors":"Tang Liu, Yuxin Lin, Lin Sang, Fei Wang, Jiawei Hu, Kun Guo, Shanglian Ju, Yiping Zhao, Xiaohong Shu","doi":"10.36922/ijb.3416","DOIUrl":"https://doi.org/10.36922/ijb.3416","url":null,"abstract":"Bone bionics and structural engineering have played a vital role in bone regeneration, with artificial scaffolds generating widespread interest. However, the mechanical properties and bone regeneration potential of biomimetic structures remain unclear. Herein, biodegradable polymer composites based on poly(butylene adipate-co-terephthalate)/poly(lactic acid) (PBAT/PLA) were 3D-printed into lattice structures as tissue engineering scaffolds. For structural design, graded diamond (D) minimal surfaces were proposed and designed to mimic the natural bone structure. The graded topologies were realized by designing gradient thickness either radially from center to edge or vertically from top to bottom. The mechanical performance of these graded samples displayed better load-carrying and energy absorption capacity than the uniform counterparts. No obvious damage was detected in the internal microstructure of the compressed samples using computed tomography. Subsequently, platelet-rich plasma (PRP), containing diverse cytokines, was loaded on the graded scaffolds. The PRP-loaded D-scaffold reported improved in vitro cell proliferation and osteoblast differentiation. Finally, femoral condyle defect repair results indicated that the PRP-loaded D-scaffold effectively promoted early-stage bone regeneration. Overall, this work provides insights into fabricating artificial scaffolds with bioactive factors and biomimetic lattice structures.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":6.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141690528","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}
I. Radu, Derniza Cozorici, M. Necolau, Roxana Cristina Popescu, Eugenia Tanasa, Laurentia Alexandrescu, Cătălin Zaharia, Rafael Luque
Cardiovascular diseases, a leading cause of global mortality, are driving increased demand for artificial blood vessels for surgical repair. This study discloses the fabrication of three-dimensional (3D)-printed small blood vessels as tissue-engineered grafts. Large-diameter artery and vein grafts are readily available in the market, but small-diameter blood vessels face issues due to the lack of suitable materials. Lysine-biofunctionalized and unmodified poly(vinyl alcohol) grafts (PVA grafts) (2 mm inner diameter and 3 mm outer diameter) suitable for veins and venules were designed using Fusion 360 software, Autodesk Fusion. The PVA channels were fabricated from the 3D virtual model through fused deposition modeling using a PVA filament. These channels underwent thermal treatment to adjust their crystallinity, chemical crosslinking, and functionalization to optimize their mechanical properties and biocompatibility. Crosslinking and biofunctionalization were assessed using Fourier-transform infrared spectroscopy with attenuated total reflectance, while X-ray diffraction and differential scanning calorimetry were utilized for structural analysis. PVA grafts were biologically tested using three specific types of cell cultures: bEnd.3 brain endothelial cells, L929 fibroblast cells, and U937 monocyte-like cells. The hemocompatibility of the optimized vascular grafts was evaluated using horse blood, following the guidelines outlined in ASTM F756-13 Standard Practice for Assessment of Hemolytic Properties of Materials. The direct method for hemoglobin determination was specifically employed. Additionally, we developed an external polyethylene terephthalate glycol (PETG) 3D-printed platform to house the PVA grafts in parallel. The assembled platform (PETG and PVA graft) was connected to both an inlet and an outlet to facilitate the passage of an aqueous flow through the internal section of the PVA grafts during a flow test conducted under simulated body conditions (vacuum and blood pressure: 40 mbar). The flow was induced by a vacuum pump connected to the outlet of the platform, while the inlet was connected to a feeding glass. In summation, we have established a suitable protocol for producing small vascular grafts and demonstrated that the optimization process could significantly affect graft properties.
{"title":"Engineered 3D-printed poly(vinyl alcohol) vascular grafts: Impact of thermal treatment and functionalization","authors":"I. Radu, Derniza Cozorici, M. Necolau, Roxana Cristina Popescu, Eugenia Tanasa, Laurentia Alexandrescu, Cătălin Zaharia, Rafael Luque","doi":"10.36922/ijb.2193","DOIUrl":"https://doi.org/10.36922/ijb.2193","url":null,"abstract":"Cardiovascular diseases, a leading cause of global mortality, are driving increased demand for artificial blood vessels for surgical repair. This study discloses the fabrication of three-dimensional (3D)-printed small blood vessels as tissue-engineered grafts. Large-diameter artery and vein grafts are readily available in the market, but small-diameter blood vessels face issues due to the lack of suitable materials. Lysine-biofunctionalized and unmodified poly(vinyl alcohol) grafts (PVA grafts) (2 mm inner diameter and 3 mm outer diameter) suitable for veins and venules were designed using Fusion 360 software, Autodesk Fusion. The PVA channels were fabricated from the 3D virtual model through fused deposition modeling using a PVA filament. These channels underwent thermal treatment to adjust their crystallinity, chemical crosslinking, and functionalization to optimize their mechanical properties and biocompatibility. Crosslinking and biofunctionalization were assessed using Fourier-transform infrared spectroscopy with attenuated total reflectance, while X-ray diffraction and differential scanning calorimetry were utilized for structural analysis. PVA grafts were biologically tested using three specific types of cell cultures: bEnd.3 brain endothelial cells, L929 fibroblast cells, and U937 monocyte-like cells. The hemocompatibility of the optimized vascular grafts was evaluated using horse blood, following the guidelines outlined in ASTM F756-13 Standard Practice for Assessment of Hemolytic Properties of Materials. The direct method for hemoglobin determination was specifically employed. Additionally, we developed an external polyethylene terephthalate glycol (PETG) 3D-printed platform to house the PVA grafts in parallel. The assembled platform (PETG and PVA graft) was connected to both an inlet and an outlet to facilitate the passage of an aqueous flow through the internal section of the PVA grafts during a flow test conducted under simulated body conditions (vacuum and blood pressure: 40 mbar). The flow was induced by a vacuum pump connected to the outlet of the platform, while the inlet was connected to a feeding glass. In summation, we have established a suitable protocol for producing small vascular grafts and demonstrated that the optimization process could significantly affect graft properties.","PeriodicalId":48522,"journal":{"name":"International Journal of Bioprinting","volume":null,"pages":null},"PeriodicalIF":8.4,"publicationDate":"2024-06-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141363235","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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