Grant Scull, Jacob D. Thompson, Melika Osareh, Ysabel Rey, Adrian Aligwekwe, Sofie Finkelstein, Lauren V. Schnabel, Matthew B. Fisher, Ashley Brown
Musculoskeletal knee injuries are common and debilitating, with the most prevalent soft tissue injuries being anterior cruciate ligament (ACL) and meniscal tears. These tears do not heal well naturally, and biological therapies involving scaffolds are often unsuccessful, due in part to the synovial fluid environment of the joint. Viscous synovial fluid contains high concentrations of degradative enzymes, including plasmin, which prevents the stable formation of provisional fibrin scaffolds. Lack of provisional scaffold formation prevents bridging of torn tissue and subsequent remodeling for permanent tissue repair. Coagulation factors such as fibrinogen and thrombin, reinforced with synthetic platelet-like particles (PLPs), can be introduced to synovial fluid to promote fibrin scaffold formation. PLPs bind to and retract fibrin fibers to enhance stiffness, density, and stability of fibrin scaffolds. Therefore, the objective of this work is to investigate the role of PLPs in enhancing fibrin scaffold formation and degradation capabilities within synovial fluid and to characterize the resulting scaffold structure, density, and mechanics. We investigated effects in synovial fluid with high or low viscosity, as viscosity can change with injury and can vary between individuals. Following the addition of clotting factors and PLPs to synovial fluid, we found an increase in fibrin scaffold density, structure, and maximum mechanics for low viscosity, but not high viscosity, synovial fluid groups. Furthermore, by lowering the viscosity of synovial fluid with hyaluronidase, the increase in scaffold density following PLP addition was restored, indicating the strong role of synovial fluid viscosity on stable scaffold formation. This technology contributes to the development of a more robust fibrin-based therapy for intra-articular musculoskeletal injuries.
{"title":"Noninvasive Fibrin Targeting Colloid-Mediated Intra-Articular Repair","authors":"Grant Scull, Jacob D. Thompson, Melika Osareh, Ysabel Rey, Adrian Aligwekwe, Sofie Finkelstein, Lauren V. Schnabel, Matthew B. Fisher, Ashley Brown","doi":"10.1002/jbm.a.37901","DOIUrl":"https://doi.org/10.1002/jbm.a.37901","url":null,"abstract":"<p>Musculoskeletal knee injuries are common and debilitating, with the most prevalent soft tissue injuries being anterior cruciate ligament (ACL) and meniscal tears. These tears do not heal well naturally, and biological therapies involving scaffolds are often unsuccessful, due in part to the synovial fluid environment of the joint. Viscous synovial fluid contains high concentrations of degradative enzymes, including plasmin, which prevents the stable formation of provisional fibrin scaffolds. Lack of provisional scaffold formation prevents bridging of torn tissue and subsequent remodeling for permanent tissue repair. Coagulation factors such as fibrinogen and thrombin, reinforced with synthetic platelet-like particles (PLPs), can be introduced to synovial fluid to promote fibrin scaffold formation. PLPs bind to and retract fibrin fibers to enhance stiffness, density, and stability of fibrin scaffolds. Therefore, the objective of this work is to investigate the role of PLPs in enhancing fibrin scaffold formation and degradation capabilities within synovial fluid and to characterize the resulting scaffold structure, density, and mechanics. We investigated effects in synovial fluid with high or low viscosity, as viscosity can change with injury and can vary between individuals. Following the addition of clotting factors and PLPs to synovial fluid, we found an increase in fibrin scaffold density, structure, and maximum mechanics for low viscosity, but not high viscosity, synovial fluid groups. Furthermore, by lowering the viscosity of synovial fluid with hyaluronidase, the increase in scaffold density following PLP addition was restored, indicating the strong role of synovial fluid viscosity on stable scaffold formation. This technology contributes to the development of a more robust fibrin-based therapy for intra-articular musculoskeletal injuries.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37901","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707292","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Rudolph J. Kashinga, Xuezhi Cao, Lukas Masseling, Felix Vogt, Nicole Schaaps, Liguo Zhao
Currently, percutaneous coronary intervention, based on stenting, is employed to provide scaffolding support to correct occlusion and diminished blood supply caused by atherosclerosis. To guarantee procedural efficacy and enhanced structural integrity of stents, further developments of stent materials and manufacturing methods are particularly required. In this paper, 316L stainless steel stents fabricated by additive manufacturing are studied through heat treatment, microstructural characterization, and mechanical deformation in vitro. After solution heat treatment conducted at 1200°C for durations ranging from 1 to 4 h, coarsening of columnar grains and changes in the grain boundary characters were observed, indicating the potential of microstructure modification through heat treatment. Electrochemical polishing can effectively improve surface quality by dissolving surface imperfections caused by partially sintered powders and uneven solidification processes, characteristics of additively manufactured parts. Mechanical deformation behaviors are evaluated by expansion tests before and after heat treatment. Specifically, free expansion tests are carried out to assess the mechanical performance of the stent alone, while in vitro mechanical performances are evaluated using silicone arteries filled with silicone plaques, corresponding to a stenosis rate of 70%. Coarsened grain microstructures in heat-treated stents lead to improved expansion flexibility, reduced dog-boning ratio, and slightly increased recoil, as compared to the as-printed stents. Results demonstrate the viability of improving the mechanical performance of additively manufactured 316L stainless steel stents through heat treatment process.
{"title":"Effects of Heat Treatment on Microstructure Change and Mechanical Performance of Additively Manufactured 316L Stainless Steel Stents","authors":"Rudolph J. Kashinga, Xuezhi Cao, Lukas Masseling, Felix Vogt, Nicole Schaaps, Liguo Zhao","doi":"10.1002/jbm.a.37904","DOIUrl":"https://doi.org/10.1002/jbm.a.37904","url":null,"abstract":"<div>\u0000 \u0000 <p>Currently, percutaneous coronary intervention, based on stenting, is employed to provide scaffolding support to correct occlusion and diminished blood supply caused by atherosclerosis. To guarantee procedural efficacy and enhanced structural integrity of stents, further developments of stent materials and manufacturing methods are particularly required. In this paper, 316L stainless steel stents fabricated by additive manufacturing are studied through heat treatment, microstructural characterization, and mechanical deformation in vitro. After solution heat treatment conducted at 1200°C for durations ranging from 1 to 4 h, coarsening of columnar grains and changes in the grain boundary characters were observed, indicating the potential of microstructure modification through heat treatment. Electrochemical polishing can effectively improve surface quality by dissolving surface imperfections caused by partially sintered powders and uneven solidification processes, characteristics of additively manufactured parts. Mechanical deformation behaviors are evaluated by expansion tests before and after heat treatment. Specifically, free expansion tests are carried out to assess the mechanical performance of the stent alone, while in vitro mechanical performances are evaluated using silicone arteries filled with silicone plaques, corresponding to a stenosis rate of 70%. Coarsened grain microstructures in heat-treated stents lead to improved expansion flexibility, reduced dog-boning ratio, and slightly increased recoil, as compared to the as-printed stents. Results demonstrate the viability of improving the mechanical performance of additively manufactured 316L stainless steel stents through heat treatment process.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707294","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}
Ryan M. Francis, Irina Kopyeva, Nicholas Lai, Shiyu Yang, Jeremy R. Filteau, Xinru Wang, David Baker, Cole A. DeForest
Hydrogels are an important class of biomaterials that permit cells to be cultured and studied within engineered microenvironments of user-defined physical and chemical properties. Though conventional 3D extrusion and stereolithographic (SLA) printing readily enable homogeneous and multimaterial hydrogels to be formed with specific macroscopic geometries, strategies that further afford spatiotemporal customization of the underlying gel physicochemistry in a non-discrete manner would be profoundly useful toward recapitulating the complexity of native tissue in vitro. Here, we demonstrate that grayscale control over local biomaterial biochemistry and mechanics can be rapidly achieved across large constructs using an inexpensive (~$300) and commercially available liquid crystal display (LCD)-based printer. Template grayscale images are first processed into a “height-extruded” 3D object, which is then printed on a standard LCD printer with an immobile build head. As the local height of the 3D object corresponds to the final light dosage delivered at the corresponding xy-coordinate, this method provides a route toward spatially specifying the extent of various dosage-dependent and biomaterial, forming/modifying photochemistries. Demonstrating the utility of this approach, we photopattern the grayscale polymerization of poly(ethylene glycol) (PEG) diacrylate gels, biochemical functionalization of agarose- and PEG-based gels via oxime ligation, and the controlled 2D adhesion and 3D growth of cells in response to a de novo-designed α5β1-modulating protein via thiol-norbornene click chemistry. Owing to the method's low cost, simple implementation, and high compatibility with many biomaterial photochemistries, we expect this strategy will prove useful toward fundamental biological studies and functional tissue engineering alike.
{"title":"Rapid and Inexpensive Image-Guided Grayscale Biomaterial Customization via LCD Printing","authors":"Ryan M. Francis, Irina Kopyeva, Nicholas Lai, Shiyu Yang, Jeremy R. Filteau, Xinru Wang, David Baker, Cole A. DeForest","doi":"10.1002/jbm.a.37897","DOIUrl":"https://doi.org/10.1002/jbm.a.37897","url":null,"abstract":"<div>\u0000 \u0000 <p>Hydrogels are an important class of biomaterials that permit cells to be cultured and studied within engineered microenvironments of user-defined physical and chemical properties. Though conventional 3D extrusion and stereolithographic (SLA) printing readily enable homogeneous and multimaterial hydrogels to be formed with specific macroscopic geometries, strategies that further afford spatiotemporal customization of the underlying gel physicochemistry in a non-discrete manner would be profoundly useful toward recapitulating the complexity of native tissue in vitro. Here, we demonstrate that grayscale control over local biomaterial biochemistry and mechanics can be rapidly achieved across large constructs using an inexpensive (~$300) and commercially available liquid crystal display (LCD)-based printer. Template grayscale images are first processed into a “height-extruded” 3D object, which is then printed on a standard LCD printer with an immobile build head. As the local height of the 3D object corresponds to the final light dosage delivered at the corresponding <i>xy</i>-coordinate, this method provides a route toward spatially specifying the extent of various dosage-dependent and biomaterial, forming/modifying photochemistries. Demonstrating the utility of this approach, we photopattern the grayscale polymerization of poly(ethylene glycol) (PEG) diacrylate gels, biochemical functionalization of agarose- and PEG-based gels via oxime ligation, and the controlled 2D adhesion and 3D growth of cells in response to a <i>de novo</i>-designed α5β1-modulating protein via thiol-norbornene click chemistry. Owing to the method's low cost, simple implementation, and high compatibility with many biomaterial photochemistries, we expect this strategy will prove useful toward fundamental biological studies and functional tissue engineering alike.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707291","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}
Patryk Romaniuk, Barbara Kołodziejska, Joanna Kolmas
Silicocarnotite (Ca5(PO4)2(SiO4)) is an inorganic crystalline material classified as a silicophosphate. Its chemical composition is similar to that of calcium hydroxyapatite (Ca10(PO4)6(OH)2) and silicon-substituted hydroxyapatite (Ca10(PO4)6-x(SiO4)x(OH)2-x-□). Given the critical role of silicon ions in bone tissue metabolism, mineralization, and collagen synthesis, silicon-enriched hydroxyapatites have long been of significant interest in regenerative medicine. The natural presence of silicate ions in the structure of silicophosphates has prompted research into their synthesis and potential application as bone substitute materials in reconstructive and reparative bone surgery. This article reviews the current state of knowledge on silicocarnotite, including its physicochemical and biological properties, the application potential, and prospective research directions.
{"title":"Silicocarnotite—A New Ceramic Material With Potential Application in Bone Tissue Regeneration","authors":"Patryk Romaniuk, Barbara Kołodziejska, Joanna Kolmas","doi":"10.1002/jbm.a.37902","DOIUrl":"https://doi.org/10.1002/jbm.a.37902","url":null,"abstract":"<div>\u0000 \u0000 <p>Silicocarnotite (Ca<sub>5</sub>(PO<sub>4</sub>)<sub>2</sub>(SiO<sub>4</sub>)) is an inorganic crystalline material classified as a silicophosphate. Its chemical composition is similar to that of calcium hydroxyapatite (Ca<sub>10</sub>(PO<sub>4</sub>)<sub>6</sub>(OH)<sub>2</sub>) and silicon-substituted hydroxyapatite (Ca<sub>10</sub>(PO<sub>4</sub>)<sub>6-x</sub>(SiO<sub>4</sub>)<sub>x</sub>(OH)<sub>2-x-□</sub>). Given the critical role of silicon ions in bone tissue metabolism, mineralization, and collagen synthesis, silicon-enriched hydroxyapatites have long been of significant interest in regenerative medicine. The natural presence of silicate ions in the structure of silicophosphates has prompted research into their synthesis and potential application as bone substitute materials in reconstructive and reparative bone surgery. This article reviews the current state of knowledge on silicocarnotite, including its physicochemical and biological properties, the application potential, and prospective research directions.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143707293","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}
Nicole E. Friend, Irene W. Zhang, Michael M. Hu, Atticus J. McCoy, Robert N. Kent III, Samuel J. DePalma, Brendon M. Baker, Sasha Cai Lesher-Pérez, Jan P. Stegemann, Andrew J. Putnam
Establishing a robust, functional microvascular network remains a critical challenge for both the revascularization of damaged or diseased tissues and the development of engineered biological materials. Vascularizing microgels may aid in efforts to develop complex, multiphasic tissues by providing discrete, vascularized tissue modules that can be distributed throughout engineered constructs to vascularize large volumes. Here, we fabricated poly(ethylene glycol)-norbornene (PEGNB) microgels containing endothelial and stromal cells via flow-focusing microfluidic droplet generation. When embedded in bulk fibrin hydrogels, these cell-laden microgels initiated the formation and development of robust microvascular networks. Furthermore, extended preculture of cell-laden PEGNB microgels enabled the formation of vessel-like structures supported by basement membrane within the matrix without aggregation. Our findings highlight the suitability of PEG-based matrices for the development of vascularizing microgels capable of forming well-distributed, robust microvascular networks.
{"title":"Biofabrication and Characterization of Vascularizing PEG-Norbornene Microgels","authors":"Nicole E. Friend, Irene W. Zhang, Michael M. Hu, Atticus J. McCoy, Robert N. Kent III, Samuel J. DePalma, Brendon M. Baker, Sasha Cai Lesher-Pérez, Jan P. Stegemann, Andrew J. Putnam","doi":"10.1002/jbm.a.37900","DOIUrl":"https://doi.org/10.1002/jbm.a.37900","url":null,"abstract":"<p>Establishing a robust, functional microvascular network remains a critical challenge for both the revascularization of damaged or diseased tissues and the development of engineered biological materials. Vascularizing microgels may aid in efforts to develop complex, multiphasic tissues by providing discrete, vascularized tissue modules that can be distributed throughout engineered constructs to vascularize large volumes. Here, we fabricated poly(ethylene glycol)-norbornene (PEGNB) microgels containing endothelial and stromal cells via flow-focusing microfluidic droplet generation. When embedded in bulk fibrin hydrogels, these cell-laden microgels initiated the formation and development of robust microvascular networks. Furthermore, extended preculture of cell-laden PEGNB microgels enabled the formation of vessel-like structures supported by basement membrane within the matrix without aggregation. Our findings highlight the suitability of PEG-based matrices for the development of vascularizing microgels capable of forming well-distributed, robust microvascular networks.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37900","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698732","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Yuzhuo Wang, Chao Yin, Xiangguang Lu, Xiaoyue Shang, Mingcheng Fan, Jing Huang, Chunyu Guo, Hongjie Ji, Min Wang
Gastrectomy is often associated with serious complications that lack effective treatments. Despite the widespread adoption in tissue engineering, the rapid degradation of small intestinal submucosa (SIS) compromised its performance in gastric tissue engineering. Thereby, genipin, a natural crosslinking agent, was employed to modify SIS, and the potential of genipin-crosslinked SIS (GP-SIS) in promoting the regeneration of full-thickness gastric defects was explored. The data on crosslinking efficiency demonstrated that genipin can efficiently fix SIS. GP-SIS exhibited high resistance against collagenase, enhanced hydrothermal stability, and improved mechanical properties according to in vitro degradation, shrinkage temperature, and uniaxial tensile tests. Additionally, GP-SIS maintained excellent biocompatibility based on a cytotoxicity test and rat subcutaneous implantation. In the rat full-thickness gastric wall defect model, GP-SIS, serving as a protective barrier, accelerated the newly formed granulation tissues and fibrosis, avoiding the occurrence of gastric leakage. Its niche and growth factors further promoted the vascularization and epithelialization of the regenerated area. In conclusion, GP-SIS will be feasible in the near future for gastric wall reconstruction after gastrectomy.
{"title":"Evaluation of Genipin-Crosslinked Small Intestinal Submucosa for a Full-Thickness Gastric Defect Repair","authors":"Yuzhuo Wang, Chao Yin, Xiangguang Lu, Xiaoyue Shang, Mingcheng Fan, Jing Huang, Chunyu Guo, Hongjie Ji, Min Wang","doi":"10.1002/jbm.a.37899","DOIUrl":"https://doi.org/10.1002/jbm.a.37899","url":null,"abstract":"<div>\u0000 \u0000 <p>Gastrectomy is often associated with serious complications that lack effective treatments. Despite the widespread adoption in tissue engineering, the rapid degradation of small intestinal submucosa (SIS) compromised its performance in gastric tissue engineering. Thereby, genipin, a natural crosslinking agent, was employed to modify SIS, and the potential of genipin-crosslinked SIS (GP-SIS) in promoting the regeneration of full-thickness gastric defects was explored. The data on crosslinking efficiency demonstrated that genipin can efficiently fix SIS. GP-SIS exhibited high resistance against collagenase, enhanced hydrothermal stability, and improved mechanical properties according to in vitro degradation, shrinkage temperature, and uniaxial tensile tests. Additionally, GP-SIS maintained excellent biocompatibility based on a cytotoxicity test and rat subcutaneous implantation. In the rat full-thickness gastric wall defect model, GP-SIS, serving as a protective barrier, accelerated the newly formed granulation tissues and fibrosis, avoiding the occurrence of gastric leakage. Its niche and growth factors further promoted the vascularization and epithelialization of the regenerated area. In conclusion, GP-SIS will be feasible in the near future for gastric wall reconstruction after gastrectomy.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 4","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143698731","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}
Jesse Augusto Pereira, Victor Martin, Rita Araújo, Liliana Grenho, Pedro Gomes, Joana Marto, Maria Helena Fernandes, Catarina Santos, Cristiane Duque
Considering the search for new biocompatible intracanal medicaments that can preserve remaining cells and stimulate bone tissue repair in the periapical region, this study aimed to synthesize and characterize the physicochemical properties of morin-loaded chitosan-poloxamer hydrogel (MCP) as well as to evaluate its osteogenic potential. Morin hydrate (M) was loaded into chitosan-poloxamer (CP) hydrogel and the resulting particles were characterized by infrared spectroscopy (FTIR), UV–vis spectrophotometer and scanning electron microscopy. Biological assays evaluated the metabolic activity, cell morphology and alkaline phosphatase (ALP) activity of human bone marrow stem cells (HBMSC) in three different settings, such as the exposure to dissolved morin, hydrogel's leachates and assembled particles by indirect contact. Cells cultured in standard culture conditions were used as control. The effect of CP and MCP particles on the formation of collagenous and mineralized tissues was also assessed within the organotypic model of segmented embryonic chick femora. Datasets were assessed for one-way analysis of variance (ANOVA), followed by Tukey's post hoc test (p < 0.05). Morin at 50 μg/mL was cytocompatible and increased ALP activity. CP and MCP particles showed stability, and morin was entrapped in the hydrogel matrix without changing its chemical structure. Cultures treated with 30-min CP and MCP hydrogel leachates presented significantly higher metabolic activity compared to control. By indirect contact, CP particles increased metabolic activity, but only MCP particles induced an upregulation of ALP activity in comparison to control. The amount of collagenous tissue and mineralized area on the fractured embryonic chick femora was greater in MCP particles compared to CP counterparts. Chitosan-poloxamer platforms are suitable systems to delivery morin, enhancing cell proliferation and bone mineralization, which upholds its application as intracanal medication for endodontic purposes.
{"title":"Morin-Loaded Chitosan-Poloxamer Hydrogel as an Osteoinductive Delivery System for Endodontic Applications","authors":"Jesse Augusto Pereira, Victor Martin, Rita Araújo, Liliana Grenho, Pedro Gomes, Joana Marto, Maria Helena Fernandes, Catarina Santos, Cristiane Duque","doi":"10.1002/jbm.a.37895","DOIUrl":"https://doi.org/10.1002/jbm.a.37895","url":null,"abstract":"<div>\u0000 \u0000 <p>Considering the search for new biocompatible intracanal medicaments that can preserve remaining cells and stimulate bone tissue repair in the periapical region, this study aimed to synthesize and characterize the physicochemical properties of morin-loaded chitosan-poloxamer hydrogel (MCP) as well as to evaluate its osteogenic potential. Morin hydrate (M) was loaded into chitosan-poloxamer (CP) hydrogel and the resulting particles were characterized by infrared spectroscopy (FTIR), UV–vis spectrophotometer and scanning electron microscopy. Biological assays evaluated the metabolic activity, cell morphology and alkaline phosphatase (ALP) activity of human bone marrow stem cells (HBMSC) in three different settings, such as the exposure to dissolved morin, hydrogel's leachates and assembled particles by indirect contact. Cells cultured in standard culture conditions were used as control. The effect of CP and MCP particles on the formation of collagenous and mineralized tissues was also assessed within the organotypic model of segmented embryonic chick femora. Datasets were assessed for one-way analysis of variance (ANOVA), followed by Tukey's post hoc test (<i>p</i> < 0.05). Morin at 50 μg/mL was cytocompatible and increased ALP activity. CP and MCP particles showed stability, and morin was entrapped in the hydrogel matrix without changing its chemical structure. Cultures treated with 30-min CP and MCP hydrogel leachates presented significantly higher metabolic activity compared to control. By indirect contact, CP particles increased metabolic activity, but only MCP particles induced an upregulation of ALP activity in comparison to control. The amount of collagenous tissue and mineralized area on the fractured embryonic chick femora was greater in MCP particles compared to CP counterparts. Chitosan-poloxamer platforms are suitable systems to delivery morin, enhancing cell proliferation and bone mineralization, which upholds its application as intracanal medication for endodontic purposes.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622584","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}
Zuzanna Michalska, Anna Ostaszewska, Martyna Fularczyk, Maria Dzierżyńska, Kacper Bielak, Justyna Morytz, Adam K. Sieradzan, Karolina Archacka, Edyta Brzoska, Sylwia Rodziewicz-Motowidło, Maria A. Ciemerych
Skeletal muscle regeneration depends on satellite cells, which, in response to injury, activate, proliferate, and reconstruct damaged tissue. However, under certain conditions, such as large injuries or myopathies, this process may not be properly executed, and muscle function may be affected. Thus, pro-regenerative actions, such as the use of various factors or cells, are widely tested as a tool to improve muscle regeneration. In the current study, we designed peptides derived from the IL-4 and SDF-1 proteins, namely IL-4-X, IL-4-Y, SDF-1-X, and SDF-1-Y. We showed that these peptides can bind to appropriate receptors and can adopt proper structure in solution. Importantly, we documented, using in vitro culture, that they do not negatively affect the cells that are present and active in skeletal muscles, such as myoblasts and fibroblasts, bone marrow stromal cells, as well as induced pluripotent stem cells, which can serve as a source of myoblasts. The presence of peptides did not affect cell proliferation compared to untreated cells. In vitro culture and differentiation protocols documented that selected IL-4 and SDF-1 peptides increased cell migration and inhibited undesirable adipogenic differentiation. Thus, we proved that these peptides are safe to use in in vivo studies aimed at improving skeletal muscle regeneration.
{"title":"In Vitro Bioactivity Evaluation of IL-4 and SDF-1 Mimicking Peptides Engineered to Enhance Skeletal Muscle Reconstruction","authors":"Zuzanna Michalska, Anna Ostaszewska, Martyna Fularczyk, Maria Dzierżyńska, Kacper Bielak, Justyna Morytz, Adam K. Sieradzan, Karolina Archacka, Edyta Brzoska, Sylwia Rodziewicz-Motowidło, Maria A. Ciemerych","doi":"10.1002/jbm.a.37898","DOIUrl":"https://doi.org/10.1002/jbm.a.37898","url":null,"abstract":"<p>Skeletal muscle regeneration depends on satellite cells, which, in response to injury, activate, proliferate, and reconstruct damaged tissue. However, under certain conditions, such as large injuries or myopathies, this process may not be properly executed, and muscle function may be affected. Thus, pro-regenerative actions, such as the use of various factors or cells, are widely tested as a tool to improve muscle regeneration. In the current study, we designed peptides derived from the IL-4 and SDF-1 proteins, namely IL-4-X, IL-4-Y, SDF-1-X, and SDF-1-Y. We showed that these peptides can bind to appropriate receptors and can adopt proper structure in solution. Importantly, we documented, using in vitro culture, that they do not negatively affect the cells that are present and active in skeletal muscles, such as myoblasts and fibroblasts, bone marrow stromal cells, as well as induced pluripotent stem cells, which can serve as a source of myoblasts. The presence of peptides did not affect cell proliferation compared to untreated cells. In vitro culture and differentiation protocols documented that selected IL-4 and SDF-1 peptides increased cell migration and inhibited undesirable adipogenic differentiation. Thus, we proved that these peptides are safe to use in in vivo studies aimed at improving skeletal muscle regeneration.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37898","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143629877","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Asrar Elahi, Warwick Duncan, Kai Chun Li, Tanmoy Bhattacharjee, Dawn Coates
Bone loss resulting in large bony defects presents a significant challenge for surgeons. In cases requiring reconstruction, bone “block” grafts that have the key attributes of both physical robustness and biocompatibility are required to facilitate bone healing and regeneration. Current technologies employed for the development of block grafts often result in constructs with suboptimal strength and integration. This study aimed to develop a bovine-derived bone block graft using the process of supercritical fluid (SCF) extraction to maintain mechanical strength and biocompatibility. Bone blocks were prepared from the condyles of bovine femurs. After optimization, the blocks were divided into six groups; Group 1: Raw bone, Group 2: SCF–CO2, Groups 3: SCF–CO2–H2O2, and Group 4: SCF–CO2–H2O2 + Pepsin. Characterization of the constructs included analysis of organic material (thermogravimetric analysis, TGA), crystallinity using x-ray diffraction (XRD), surface topography with scanning electron microscopy (SEM), and chemical composition using Fourier-transform infrared (FTIR) spectroscopy. Mechanical strength was assessed using compression testing, and clinically relevant handling was investigated with a bench-top drill test. Biological testing was carried out in vitro using human bone marrow-derived mesenchymal stem cells (hBMSCs). The SCF-treated bone blocks showed promising results with enhanced mechanical strength (raw bone [mean = 23.01 8.9 MPa], SCF–CO2–H2O2 [mean = 48.9 ± 11.6 MPa], p < 0.0001) reduced organic content (raw bone = 17.6%, SCF–CO2–H2O2 + Pepsin = 12.4%), and significantly higher hBMSCs' metabolic activity on the SCF–CO2 and SCF–CO2 + H2O2 compared to Bio-Oss at 24, 48, 72, and 96 h (p < 0.05). SEM photomicrographs showed reduced debris in trabecular structures with open pores after SCF–CO2 treatment, especially in SCF–CO2–H2O2 + Pepsin blocks. Moreover, the bench-top clinical handling test demonstrated the ease of block fixation with surgical screws. Overall, the SCF–CO2 and posttreatments of bovine block grafts showed potential for clinical application.
{"title":"Supercritical CO2 With Enzymatic Posttreatment Enhances Mechanical and Biological Properties of Cancellous Bovine Bone Block Grafts","authors":"Asrar Elahi, Warwick Duncan, Kai Chun Li, Tanmoy Bhattacharjee, Dawn Coates","doi":"10.1002/jbm.a.37896","DOIUrl":"https://doi.org/10.1002/jbm.a.37896","url":null,"abstract":"<p>Bone loss resulting in large bony defects presents a significant challenge for surgeons. In cases requiring reconstruction, bone “block” grafts that have the key attributes of both physical robustness and biocompatibility are required to facilitate bone healing and regeneration. Current technologies employed for the development of block grafts often result in constructs with suboptimal strength and integration. This study aimed to develop a bovine-derived bone block graft using the process of supercritical fluid (SCF) extraction to maintain mechanical strength and biocompatibility. Bone blocks were prepared from the condyles of bovine femurs. After optimization, the blocks were divided into six groups; Group 1: Raw bone, Group 2: SCF–CO<sub>2</sub>, Groups 3: SCF–CO<sub>2</sub>–H<sub>2</sub>O<sub>2</sub>, and Group 4: SCF–CO<sub>2</sub>–H<sub>2</sub>O<sub>2</sub> + Pepsin. Characterization of the constructs included analysis of organic material (thermogravimetric analysis, TGA), crystallinity using x-ray diffraction (XRD), surface topography with scanning electron microscopy (SEM), and chemical composition using Fourier-transform infrared (FTIR) spectroscopy. Mechanical strength was assessed using compression testing, and clinically relevant handling was investigated with a bench-top drill test. Biological testing was carried out in vitro using human bone marrow-derived mesenchymal stem cells (hBMSCs). The SCF-treated bone blocks showed promising results with enhanced mechanical strength (raw bone [mean = 23.01 8.9 MPa], SCF–CO<sub>2</sub>–H<sub>2</sub>O<sub>2</sub> [mean = 48.9 ± 11.6 MPa], <i>p</i> < 0.0001) reduced organic content (raw bone = 17.6%, SCF–CO<sub>2</sub>–H<sub>2</sub>O<sub>2</sub> + Pepsin = 12.4%), and significantly higher hBMSCs' metabolic activity on the SCF–CO<sub>2</sub> and SCF–CO<sub>2</sub> + H<sub>2</sub>O<sub>2</sub> compared to Bio-Oss at 24, 48, 72, and 96 h (<i>p</i> < 0.05). SEM photomicrographs showed reduced debris in trabecular structures with open pores after SCF–CO<sub>2</sub> treatment, especially in SCF–CO<sub>2</sub>–H<sub>2</sub>O<sub>2</sub> + Pepsin blocks. Moreover, the bench-top clinical handling test demonstrated the ease of block fixation with surgical screws. Overall, the SCF–CO<sub>2</sub> and posttreatments of bovine block grafts showed potential for clinical application.</p>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/jbm.a.37896","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143622532","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Engineering cellular microenvironments with biomaterials is an effective strategy for endothelial cell expansion and functionality in vascular tissue engineering. The basement membrane (BM) is a natural vascular endothelium microenvironment that plays an important role in promoting rapid expansion and function of endothelial cells. However, mimicking the crucial function of BM with an ideal biomaterial remains challenging. In this study, we developed a cell-derived decellularized extracellular matrix (c-dECM) paper to mimic the role of BM in endothelial cell expansion and function. The results showed that c-dECM paper was a stable, biocompatible, and biodegradable scaffold that significantly promoted endothelial cell expansion by modulating cell migration, adhesion, and proliferation both in vivo and in vitro. Moreover, the biomimetic c-dECM paper can profoundly promote endothelial cell function by increasing the synthesis and release of nitric oxide (NO) and prostaglandin I2 (PGI2) and upregulating the expression of anticoagulant and vascularized genes, including thrombomodulin (THBD), tissue factor pathway inhibitor (TFPI), endothelial growth factor (VEGF) and endoglin (CD105). These data indicate that the c-dECM is a potential biomaterial for constructing vascular tissue engineering scaffolds or developing in vitro models to study the functional mechanisms of endothelial cells.
{"title":"Cell-Derived Basal Membrane-Like Extracellular Matrix Promotes Endothelial Cell Expansion and Functionalization","authors":"Jiangwei Xiao, Kai You, Daohuan Lu, Shuwen Guan, Hengpeng Wu, Jing Gao, Yadong Tang, Shan Yu, Botao Gao","doi":"10.1002/jbm.a.37893","DOIUrl":"https://doi.org/10.1002/jbm.a.37893","url":null,"abstract":"<div>\u0000 \u0000 <p>Engineering cellular microenvironments with biomaterials is an effective strategy for endothelial cell expansion and functionality in vascular tissue engineering. The basement membrane (BM) is a natural vascular endothelium microenvironment that plays an important role in promoting rapid expansion and function of endothelial cells. However, mimicking the crucial function of BM with an ideal biomaterial remains challenging. In this study, we developed a cell-derived decellularized extracellular matrix (c-dECM) paper to mimic the role of BM in endothelial cell expansion and function. The results showed that c-dECM paper was a stable, biocompatible, and biodegradable scaffold that significantly promoted endothelial cell expansion by modulating cell migration, adhesion, and proliferation both in vivo and in vitro. Moreover, the biomimetic c-dECM paper can profoundly promote endothelial cell function by increasing the synthesis and release of nitric oxide (NO) and prostaglandin I2 (PGI2) and upregulating the expression of anticoagulant and vascularized genes, including <i>thrombomodulin</i> (<i>THBD</i>), <i>tissue factor pathway inhibitor</i> (<i>TFPI</i>), <i>endothelial growth factor</i> (<i>VEGF</i>) and <i>endoglin</i> (<i>CD105</i>). These data indicate that the c-dECM is a potential biomaterial for constructing vascular tissue engineering scaffolds or developing in vitro models to study the functional mechanisms of endothelial cells.</p>\u0000 </div>","PeriodicalId":15142,"journal":{"name":"Journal of biomedical materials research. Part A","volume":"113 3","pages":""},"PeriodicalIF":3.9,"publicationDate":"2025-03-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143581811","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}