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1.
J Mater Chem B ; 12(23): 5571-5572, 2024 Jun 12.
Article En | MEDLINE | ID: mdl-38832500

Injectable hydrogels have emerged as intelligent and versatile materials that have been proven to possess huge potential for many biomedical applications including drug delivery, tissue engineering, and regenerative medicine. Hydrogels are a class of polymers with highly hydrated 3D networks that have microenvironmental properties such as oxygen/nutrient permeability that are similar to the native extracellular matrix. In addition to possessing the typical advantages of conventional hydrogels, injectable hydrogels offer extra unique features, enabling minimally invasive injectability and durability for irregularly shaped sites, and the possibility of processing these materials via, e.g., additive manufacturing techniques. As such, there has been a growing interest in using injectable hydrogels as scaffolds/carriers for therapeutic agents, including but not limited to drugs, cells, proteins, and bioactive molecules, targeted to treat chronic diseases including cancer, but also to facilitate the repair and regeneration of damaged organs/tissues. In this themed collection of Journal of Materials Chemistry B and Biomaterials Science, we include outstanding contributions covering recent developments in this rapidly evolving field of injectable hydrogels including emerging chemistries, synthesis pathways, fabrication methods, cell-material interaction, in vitro, ex vivo and in vivo performances, and subsequent targeted applications (drug delivery, tissue engineering and regenerative medicine) of injectable hydrogels.


Biocompatible Materials , Hydrogels , Injections , Tissue Engineering , Hydrogels/chemistry , Humans , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Biocompatible Materials/chemical synthesis , Regenerative Medicine/methods , Drug Delivery Systems , Animals
2.
Biol Pharm Bull ; 47(6): 1072-1078, 2024.
Article En | MEDLINE | ID: mdl-38825460

In previous studies, my group developed cell-adhesive peptide-polysaccharide complexes as biomaterials for tissue engineering. Having a wide variety of cell-adhesive peptides is important as the biological functions of peptide-polysaccharide complexes are highly dependent on the biological activity of peptides. This paper reviews the biological activities of two types of recently characterized cell-adhesive peptides. The first is peptides rich in basic amino acids originating from octaarginine. We analyzed the relationships between the amino acid composition of basic peptides and cell adhesion, elongation, and proliferation and identified the most suitable peptide for cell culture. The second was arginine-glycine-aspartic acid (RGD)-containing peptides that promote the adhesion of induced pluripotent stem cells (iPSCs). We identified the RGD-surrounding sequences necessary for iPSC adhesion, clarified the underlying mechanism, and improved cell adhesion by modifying the structure-activity relationships. The novel cell-adhesive peptides identified in our previous studies may aid in the development of novel peptide-based biomaterials.


Biocompatible Materials , Cell Adhesion , Peptides , Cell Adhesion/drug effects , Biocompatible Materials/chemistry , Humans , Peptides/pharmacology , Peptides/chemistry , Animals , Oligopeptides/chemistry , Oligopeptides/pharmacology , Tissue Engineering/methods , Induced Pluripotent Stem Cells/cytology
3.
Carbohydr Polym ; 339: 122232, 2024 Sep 01.
Article En | MEDLINE | ID: mdl-38823905

In this study, new types of hybrid double-network (DN) hydrogels composed of polyvinyl alcohol (PVA), chitosan (CH), and sodium alginate (SA) are introduced, with the hypothesis that this combination and incorporating multi-walled carbon nanotubes (MWCNTs) and graphene nanoplatelets (GNPs) will enhance osteogenetic differentiation and the structural and mechanical properties of scaffolds for bone tissue engineering applications. Initially, the impact of varying mass ratios of the PVA/CH/SA mixture on mechanical properties, swelling ratio, and degradability was examined. Based on this investigation, a mass ratio of 4:6:6 was determined to be optimal. At this ratio, the hydrogel demonstrated a Young's modulus of 47.5 ± 5 kPa, a swelling ratio of 680 ± 6 % after 3 h, and a degradation rate of 46.5 ± 5 % after 40 days. In the next phase, following the determination of the optimal mass ratio, CNTs and GNPs were incorporated into the 4:6:6 composite resulting in a significant enhancement in the electrical conductivity and stiffness of the scaffolds. The introduction of CNTs led to a notable increase of 36 % in the viability of MG63 osteoblast cells. Additionally, the inhibition zone test revealed that GNPs and CNTs increased the diameter of the inhibition zone by 49.6 % and 52.6 %, respectively.


Alginates , Bone Regeneration , Chitosan , Hydrogels , Polyvinyl Alcohol , Tissue Engineering , Tissue Scaffolds , Chitosan/chemistry , Alginates/chemistry , Alginates/pharmacology , Polyvinyl Alcohol/chemistry , Tissue Scaffolds/chemistry , Humans , Bone Regeneration/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Tissue Engineering/methods , Nanotubes, Carbon/chemistry , Osteoblasts/drug effects , Osteoblasts/cytology , Graphite/chemistry , Graphite/pharmacology , Biomimetic Materials/chemistry , Biomimetic Materials/pharmacology , Cell Survival/drug effects , Cell Line
4.
Carbohydr Polym ; 339: 122251, 2024 Sep 01.
Article En | MEDLINE | ID: mdl-38823918

In this study, the disulfide-linked hyaluronic acid (HA) hydrogels were optimised for potential application as a scaffold in tissue engineering through the Quality by Design (QbD) approach. For this purpose, HA was first modified by incorporating the cysteine moiety into the HA backbone, which promoted the formation of disulfide cross-linked HA hydrogel at physiological pH. Utilising a Design of Experiments (DoE) methodology, the critical factors to achieve stable biomaterials, i.e. the degree of HA substitution, HA molecular weight, and coupling agent ratio, were explored. To establish a design space, the DoE was performed with 65 kDa, 138 kDa and 200 kDa HA and variable concentrations of coupling agent to optimise conditions to obtain HA hydrogel with improved rheological properties. Thus, HA hydrogel with a 12 % degree of modification, storage modulus of ≈2321 Pa and loss modulus of ≈15 Pa, was achieved with the optimum ratio of coupling agent. Furthermore, biocompatibility assessments in C28/I2 chondrocyte cells demonstrated the non-toxic nature of the hydrogel, underscoring its potential for tissue regeneration. Our findings highlight the efficacy of the QbD approach in designing HA hydrogels with tailored properties for biomedical applications.


Biocompatible Materials , Chondrocytes , Disulfides , Hyaluronic Acid , Hydrogels , Rheology , Tissue Engineering , Hyaluronic Acid/chemistry , Hydrogels/chemistry , Hydrogels/chemical synthesis , Disulfides/chemistry , Chondrocytes/drug effects , Chondrocytes/cytology , Biocompatible Materials/chemistry , Biocompatible Materials/chemical synthesis , Tissue Engineering/methods , Tissue Scaffolds/chemistry , Animals , Cell Line , Cell Survival/drug effects , Humans , Hydrogen-Ion Concentration
5.
Carbohydr Polym ; 339: 122174, 2024 Sep 01.
Article En | MEDLINE | ID: mdl-38823938

Segmental bone defects can arise from trauma, infection, metabolic bone disorders, or tumor removal. Hydrogels have gained attention in the field of bone regeneration due to their unique hydrophilic properties and the ability to customize their physical and chemical characteristics to serve as scaffolds and carriers for growth factors. However, the limited mechanical strength of hydrogels and the rapid release of active substances have hindered their clinical utility and therapeutic effectiveness. With ongoing advancements in material science, the development of injectable and biofunctionalized hydrogels holds great promise for addressing the challenges associated with segmental bone defects. In this study, we incorporated lyophilized platelet-rich fibrin (LPRF), which contains a multitude of growth factors, into a genipin-crosslinked gelatin/hyaluronic acid (GLT/HA-0.5 % GP) hydrogel to create an injectable and biofunctionalized composite material. Our findings demonstrate that this biofunctionalized hydrogel possesses optimal attributes for bone tissue engineering. Furthermore, results obtained from rabbit model with segmental tibial bone defects, indicate that the treatment with this biofunctionalized hydrogel resulted in increased new bone formation, as confirmed by imaging and histological analysis. From a translational perspective, this biofunctionalized hydrogel provides innovative and bioinspired capabilities that have the potential to enhance bone repair and regeneration in future clinical applications.


Bone Regeneration , Freeze Drying , Gelatin , Hyaluronic Acid , Hydrogels , Iridoids , Platelet-Rich Fibrin , Animals , Iridoids/chemistry , Iridoids/pharmacology , Gelatin/chemistry , Rabbits , Hydrogels/chemistry , Hydrogels/pharmacology , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Bone Regeneration/drug effects , Platelet-Rich Fibrin/chemistry , Tissue Engineering/methods , Cross-Linking Reagents/chemistry , Tissue Scaffolds/chemistry , Tibia/drug effects , Tibia/surgery
6.
Cell Mol Biol (Noisy-le-grand) ; 70(6): 135-141, 2024 Jun 05.
Article En | MEDLINE | ID: mdl-38836669

Epigenetic change has been found to play an important role in cell differentiation and regulation and the dental pulp stem cell in tissue engineering is gaining attention due to the ability of cells to differentiate into odontoblast and other cells. This study evaluated the influence of poly L- lactic acid with hydroxyapatite-coated with polyaniline scaffold (PLLA/HA/PANI) on dental pulp stem cell (DPSC) proliferation and differentiation. After scaffold preparation and DPSCs seeding, the cells proliferation and differentiation were evaluated by immunocytochemistry assay and cell viability was measured by cytotoxicity / MTT assay. The results showed (PLLA/HA/PANI) scaffold facilitates DPSC proliferation and differentiation with gene expression. This finding underscores the promise of this biomaterial combination as a scaffold for dental tissue regeneration and application.


Biocompatible Materials , Cell Differentiation , Cell Proliferation , Dental Pulp , Durapatite , Odontoblasts , Osteoblasts , Stem Cells , Tissue Scaffolds , Dental Pulp/cytology , Humans , Cell Differentiation/drug effects , Odontoblasts/cytology , Odontoblasts/drug effects , Odontoblasts/metabolism , Tissue Scaffolds/chemistry , Stem Cells/cytology , Stem Cells/metabolism , Stem Cells/drug effects , Osteoblasts/cytology , Osteoblasts/drug effects , Osteoblasts/metabolism , Cell Proliferation/drug effects , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Durapatite/chemistry , Durapatite/pharmacology , Aniline Compounds/pharmacology , Aniline Compounds/chemistry , Polyesters/chemistry , Polyesters/pharmacology , Cell Survival/drug effects , Cells, Cultured , Tissue Engineering/methods
7.
Sci Rep ; 14(1): 12750, 2024 06 03.
Article En | MEDLINE | ID: mdl-38830952

The current practice of restoring the anatomical structure in the treatment of pelvic floor dysfunction includes implantation of synthetic sling, which carries potential complications. This study aimed to develop biological substitutes to improve tissue function using scaffolds as a support to the host cells, through formation of new tissue. Human amniotic fluid stem cells (hAFSCs) were seeded on synthetic mesh-scaffold of AlloDerm Regenerative Tissue Matrix (RTM), Poly-DL-lactico-glycolic acid (PLGA) mesh (VICRYL) and Polydioxanone (PDS) meshes. In vitro study evaluates the metabolic activity of hAFSCs seeded mesh-scaffolds. In vivo study involving Sprague-Dawley rats was performed by assigning into 7 groups of sham control with fascia operation, AlloDerm implant, PDS implant, PLGA implant, AlloDerm harvest with hAFSC (AlloDerm-SC), PDS harvest with hAFSC(PDS-SC) and PLGS harvest with hAFSC (PGLA-SC). In vitro study reveals cell viability and proliferation of hAFSC on mesh scaffolds varies between meshes, with AlloDerm growing the fastest. The biomechanical properties of tissue-mesh-complex tension strength declined over time, showing highest tension strength on week-1, deteriorated similar to control group on week-12. All hAFSC-seeded mesh provides higher tension strength, compared to without. This study shed the potential of synthetic mesh as a scaffold for hAFSC for the surgical treatment of pelvic floor dysfunction.


Amniotic Fluid , Rats, Sprague-Dawley , Stem Cells , Tissue Scaffolds , Animals , Tissue Scaffolds/chemistry , Humans , Amniotic Fluid/cytology , Rats , Stem Cells/cytology , Female , Plastic Surgery Procedures/methods , Tissue Engineering/methods , Surgical Mesh , Cell Proliferation , Pelvic Floor/surgery , Polylactic Acid-Polyglycolic Acid Copolymer/chemistry
8.
Sci Adv ; 10(23): eadn2689, 2024 Jun 07.
Article En | MEDLINE | ID: mdl-38838141

Organ-on-chip (OOC) systems are revolutionizing tissue engineering by providing dynamic models of tissue structure, organ-level function, and disease phenotypes using human cells. However, nonbiological components of OOC devices often limit the recapitulation of in vivo-like tissue-tissue cross-talk and morphogenesis. Here, we engineered a kidney glomerulus-on-a-chip that recapitulates glomerular morphogenesis and barrier function using a biomimetic ultrathin membrane and human-induced pluripotent stem cells. The resulting chip comprised a proximate epithelial-endothelial tissue interface, which reconstituted the selective molecular filtration function of healthy and diseased kidneys. In addition, fenestrated endothelium was successfully induced from human pluripotent stem cells in an OOC device, through in vivo-like paracrine signaling across the ultrathin membrane. Thus, this device provides a dynamic tissue engineering platform for modeling human kidney-specific morphogenesis and function, enabling mechanistic studies of stem cell differentiation, organ physiology, and pathophysiology.


Kidney , Lab-On-A-Chip Devices , Morphogenesis , Tissue Engineering , Humans , Tissue Engineering/methods , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/metabolism , Kidney Glomerulus/metabolism , Kidney Glomerulus/cytology , Cell Differentiation , Membranes, Artificial
9.
Sci Rep ; 14(1): 13174, 2024 06 07.
Article En | MEDLINE | ID: mdl-38849457

Due to its structural and functional complexity the heart imposes immense physical, physiological and electromechanical challenges on the engineering of a biological replacement. Therefore, to come closer to clinical translation, the development of a simpler biological assist device is requested. Here, we demonstrate the fabrication of tubular cardiac constructs with substantial dimensions of 6 cm in length and 11 mm in diameter by combining human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs) and human foreskin fibroblast (hFFs) in human fibrin employing a rotating mold technology. By centrifugal forces employed in the process a cell-dense layer was generated enabling a timely functional coupling of iPSC-CMs demonstrated by a transgenic calcium sensor, rhythmic tissue contractions, and responsiveness to electrical pacing. Adjusting the degree of remodeling as a function of hFF-content and inhibition of fibrinolysis resulted in stable tissue integrity for up to 5 weeks. The rotating mold device developed in frame of this work enabled the production of tubes with clinically relevant dimensions of up to 10 cm in length and 22 mm in diameter which-in combination with advanced bioreactor technology for controlled production of functional iPSC-derivatives-paves the way towards the clinical translation of a biological cardiac assist device.


Fibrinogen , Induced Pluripotent Stem Cells , Myocytes, Cardiac , Tissue Engineering , Humans , Myocytes, Cardiac/metabolism , Myocytes, Cardiac/cytology , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/metabolism , Fibrinogen/metabolism , Fibrinogen/chemistry , Tissue Engineering/methods , Fibroblasts/metabolism , Cell Differentiation , Cells, Cultured , Bioreactors , Fibrin/metabolism , Fibrin/chemistry , Tissue Scaffolds/chemistry
10.
J Nanobiotechnology ; 22(1): 322, 2024 Jun 08.
Article En | MEDLINE | ID: mdl-38849858

The ideal tissue engineering scaffold should facilitate rapid cell infiltration and provide an optimal immune microenvironment during interactions with the host. Electrospinning can produce two-dimensional (2D) membranes mimicking the extracellular matrix. However, their dense structure hinders cell penetration, and their thin form restricts scaffold utility. In this study, latticed hydrogels were three-dimensional (3D) printed onto electrospun membranes. This technique allowed for layer-by-layer assembly of the membranes into 3D scaffolds, which maintained their resilience impressively under both dry and wet conditions. We assessed the cellular and host responses of these 3D nanofiber scaffolds by comparing random membranes and mesh-like membranes with three different mesh sizes (250, 500, and 750 µm). It was found that scaffolds with a mesh size of 500 µm were superior for M2 macrophage phenotype polarization, vascularization, and matrix deposition. Furthermore, it was confirmed by subsequent experiments such as RNA sequencing that the mesh-like topology may promote polarization to the M2 phenotype by affecting the PI3K/AKT pathway. In conclusion, our work offers a novel method for transforming 2D nanofiber membranes into 3D scaffolds. This method boasts flexibility, allowing for the use of varied electrospun membranes and hydrogels in terms of structure and composition. It has vast potential in tissue repair and regeneration.


Hydrogels , Nanofibers , Printing, Three-Dimensional , Regenerative Medicine , Tissue Engineering , Tissue Scaffolds , Nanofibers/chemistry , Tissue Scaffolds/chemistry , Tissue Engineering/methods , Regenerative Medicine/methods , Hydrogels/chemistry , Animals , Mice , Macrophages/metabolism , Extracellular Matrix/metabolism , Extracellular Matrix/chemistry , RAW 264.7 Cells , Humans
11.
Sci Adv ; 10(23): eado1550, 2024 Jun 07.
Article En | MEDLINE | ID: mdl-38848358

The utilization of three-dimensional (3D) bioprinting technology to create a transplantable bioartificial liver emerges as a promising remedy for the scarcity of liver donors. This study outlines our strategy for constructing a 3D-bioprinted liver, using in vitro-expanded primary hepatocytes recognized for their safety and enhanced functional robustness as hepatic cell sources for bioartificial liver construction. In addition, we have developed bioink biomaterials with mechanical and rheological properties, as well as printing capabilities, tailored for 3D bioprinting. Upon heterotopic transplantation into the mesentery of tyrosinemia or 90% hepatectomy mice, our 3D-bioprinted liver effectively restored lost liver functions, consequently extending the life span of mice afflicted with liver injuries. Notably, the inclusion of an artificial blood vessel in our 3D-bioprinted liver allowed for biomolecule exchange with host blood vessels, demonstrating, in principle, the rapid integration of the bioartificial liver into the host vascular system. This model underscores the therapeutic potential of transplantation for the treatment of liver failure diseases.


Bioprinting , Hepatocytes , Liver Failure , Liver , Printing, Three-Dimensional , Animals , Hepatocytes/metabolism , Hepatocytes/transplantation , Mice , Bioprinting/methods , Liver/metabolism , Liver Failure/therapy , Tissue Engineering/methods , Liver Transplantation/methods , Liver, Artificial , Disease Models, Animal , Tyrosinemias/therapy , Tyrosinemias/metabolism , Tissue Scaffolds/chemistry
12.
Ann Transplant ; 29: e943387, 2024 Jun 04.
Article En | MEDLINE | ID: mdl-38831572

Despite continuous and rapid progress in the transplantation of cells, tissues, and organs, many patients die before receiving them. This is because of an insufficient number of donors, which leads to a significant disproportion between the need for donors and their availability. This review aims to present the possibilities offered by alternative therapies. We use the term "functional transplantology" to describe such alternative methods of transplantation that could help change the current state of transplantation medicine. Its purpose is not to replace a defective or removed organ with another but to replace its functions using complementary biological, mechanical, or biomechanical structures or devices. Implementation of many innovative solutions shown in the work for clinical applications is already a fact. In the case of others, it should be considered a future vision. We hope that the role of a defective or damaged tissue or a group of tissues will be taken over by different structures that are functionally complementary with the organ being substituted. Undoubtedly, developing the described methods based on functional transplantology will change the face of transplantation medicine. Thus, we show current trends and new directions of thinking and actions in transplantation medicine that combine technology and transplantology. The review considers the latest technologies, including 3D bioprinting, nanotechnology, cell encapsulation, and organoids. We discuss not only the advantages of new approaches but also the limitations and challenges that must be overcome to achieve significant progress in transplantation. That is the only option to provide a safe and efficient way of improving the quality of life of many patients.


Organ Transplantation , Humans , Organ Transplantation/methods , Organ Transplantation/trends , Complementary Therapies/methods , Tissue Engineering/methods , Nanotechnology/methods , Bioprinting/methods , Printing, Three-Dimensional
13.
Clin Oral Investig ; 28(7): 361, 2024 Jun 07.
Article En | MEDLINE | ID: mdl-38847929

OBJECTIVES: To assess gingival crevicular fluid (GCF) levels of inflammatory and bone remodelling related biomarkers following transplantation of a tissue-engineered biocomplex into intrabony defects at several time-points over 12-months. MATERIALS AND METHODS: Group-A (n = 9) received the Minimal Access Flap (MAF) surgical technique combined with a biocomplex of autologous clinical-grade alveolar bone-marrow mesenchymal stem cells in collagen scaffolds enriched with an autologous fibrin/platelet lysate (aFPL). Group-B (n = 10) received the MAF surgery, with collagen scaffolds enriched with aFPL and Group-C (n = 8) received the MAF surgery alone. GCF was collected from the osseous defects of subjects via paper strips/30 sec at baseline, 6-weeks, 3-, 6-, 9-, 12-months post-surgery. Levels of inflammatory and bone remodelling-related biomarkers in GCF were determined by ELISA. RESULTS: Group-A demonstrated significantly higher GCF levels of BMP-7 at 6-9 months than baseline, with gradually decreasing levels of pro-inflammatory and pro-osteoclastogenic markers (TNF-α, RANKL) over the study-period; and an overall decrease in the RANKL/OPG ratio at 9-12 months than baseline (all p < 0.001). In comparison, only modest interim changes were observed in Groups-B and -C. CONCLUSIONS: At the protein level, the approach of MAF and biocomplex transplantation provided greater tissue regeneration potential as cell-based therapy appeared to modulate inflammation and bone remodelling in residual periodontal defects. CLINICAL RELEVANCE: Transplantation of a tissue engineered construct into periodontal intrabony defects demonstrated a biochemical pattern for inflammatory control and tissue regeneration over 12-months compared to the control treatments. Understanding the biological healing events of stem cell transplantation may facilitate the design of novel treatment strategies. CLINICAL DATABASE REGISTRATION: ClinicalTrials.gov ID: NCT02449005.


Biomarkers , Bone Remodeling , Gingival Crevicular Fluid , Tissue Engineering , Tissue Scaffolds , Humans , Bone Remodeling/physiology , Collagen , Enzyme-Linked Immunosorbent Assay , Gingival Crevicular Fluid/chemistry , Surgical Flaps , Tissue Engineering/methods , Treatment Outcome
14.
Sci Rep ; 14(1): 12945, 2024 06 05.
Article En | MEDLINE | ID: mdl-38839791

Extrusion-based bioprinting is an established method in biofabrication. Suitable bioinks have fundamentally different compositions and characteristics, which should be examined, in order to find a perfect model system. Here, we investigate the effect of two alginate-based, yet unalike 3D-printed bioinks, pre-crosslinked alginate-dialdehyde gelatin (ADA-GEL) and a mixture of alginate, hyaluronic acid, and gelatin (Alg/HA/Gel), on the melanoma cell line Mel Im and vice versa in terms of stiffness, shrinkage, cellular behavior and colony formation over 15 days. Rheological stiffness measurements revealed two soft gels with similar storage moduli. The cells did not have a significant impact on the overall stiffness, whereas ADA-GEL (2.5/2.5%) was significantly stiffer than Alg/HA/Gel (0.5/0.1/3%). Regarding the shrinkage of printed constructs, cells had a significant influence, especially in ADA-GEL, which has covalent bonds between the oxidized alginate and gelatin. Multi-photon microscopy exhibited proliferation, cell spreading and migration in ADA-GEL with cell-cell and cell-matrix interaction, dissimilarly to Alg/HA/Gel, in which cells formed spherical, encapsulated colonies. Scanning electron microscopy and histology showed degradation and multi-layered growth on ADA-GEL and fewer examples of escaped cells on Alg/HA/Gel. Both gels serve as proliferation bioink for melanoma with more necrosis in deeper Alg/HA/Gel colonies and differences in spreading and matrix interaction. These findings show the importance of proper characterization of the bioinks for different applications.


Alginates , Bioprinting , Cell Proliferation , Gelatin , Melanoma , Printing, Three-Dimensional , Alginates/chemistry , Melanoma/pathology , Cell Line, Tumor , Cell Proliferation/drug effects , Gelatin/chemistry , Bioprinting/methods , Humans , Ink , Hyaluronic Acid/chemistry , Rheology , Tissue Scaffolds/chemistry , Tissue Engineering/methods
15.
Sci Rep ; 14(1): 12975, 2024 06 05.
Article En | MEDLINE | ID: mdl-38839879

Investigating the potential of human cardiomyocytes derived from induced pluripotent stem cells (iPSC-CMs) in in vitro heart models is essential to develop cardiac regenerative medicine. iPSC-CMs are immature with a fetal-like phenotype relative to cardiomyocytes in vivo. Literature indicates methods for enhancing the structural maturity of iPSC-CMs. Among these strategies, nanofibrous scaffolds offer more accurate mimicry of the functioning of cardiac tissue structures in the human body. However, further research is needed on the use of nanofibrous mats to understand their effects on iPSC-CMs. Our research aimed to evaluate the suitability of poly(ε-caprolactone) (PCL) and polyurethane (PU) nanofibrous mats with different elasticities as materials for the maturation of iPSC-CMs. Analysis of cell morphology and orientation and the expression levels of selected genes and proteins were performed to determine the effect of the type of nanofibrous mats on the maturation of iPSC-CMs after long-term (10-day) culture. Understanding the impact of 3D structural properties in in vitro cardiac models on induced pluripotent stem cell-derived cardiomyocyte maturation is crucial for advancing cardiac tissue engineering and regenerative medicine because it can help optimize conditions for obtaining more mature and functional human cardiomyocytes.


Cell Differentiation , Induced Pluripotent Stem Cells , Myocytes, Cardiac , Nanofibers , Polyesters , Polyurethanes , Tissue Scaffolds , Humans , Myocytes, Cardiac/cytology , Myocytes, Cardiac/metabolism , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/metabolism , Polyurethanes/chemistry , Polyesters/chemistry , Nanofibers/chemistry , Cell Differentiation/drug effects , Tissue Scaffolds/chemistry , Tissue Engineering/methods , Cells, Cultured
16.
Sci Rep ; 14(1): 12721, 2024 06 03.
Article En | MEDLINE | ID: mdl-38830871

Surface structure plays a crucial role in determining cell behavior on biomaterials, influencing cell adhesion, proliferation, differentiation, as well as immune cells and macrophage polarization. While grooves and ridges stimulate M2 polarization and pits and bumps promote M1 polarization, these structures do not accurately mimic the real bone surface. Consequently, the impact of mimicking bone surface topography on macrophage polarization remains unknown. Understanding the synergistic sequential roles of M1 and M2 macrophages in osteoimmunomodulation is crucial for effective bone tissue engineering. Thus, exploring the impact of bone surface microstructure mimicking biomaterials on macrophage polarization is critical. In this study, we aimed to sequentially activate M1 and M2 macrophages using Poly-L-Lactic acid (PLA) membranes with bone surface topographical features mimicked through the soft lithography technique. To mimic the bone surface topography, a bovine femur was used as a model surface, and the membranes were further modified with collagen type-I and hydroxyapatite to mimic the bone surface microenvironment. To determine the effect of these biomaterials on macrophage polarization, we conducted experimental analysis that contained estimating cytokine release profiles and characterizing cell morphology. Our results demonstrated the potential of the hydroxyapatite-deposited bone surface-mimicked PLA membranes to trigger sequential and synergistic M1 and M2 macrophage polarizations, suggesting their ability to achieve osteoimmunomodulatory macrophage polarization for bone tissue engineering applications. Although further experimental studies are required to completely investigate the osteoimmunomodulatory effects of these biomaterials, our results provide valuable insights into the potential advantages of biomaterials that mimic the complex microenvironment of bone surfaces.


Macrophages , Polyesters , Surface Properties , Animals , Macrophages/metabolism , Macrophages/drug effects , Macrophages/immunology , Cattle , Polyesters/chemistry , Mice , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Tissue Engineering/methods , Durapatite/chemistry , Cytokines/metabolism , Bone and Bones/cytology , Cell Differentiation/drug effects , Macrophage Activation/drug effects , Cell Adhesion/drug effects , RAW 264.7 Cells , Cell Polarity/drug effects , Femur , Collagen Type I/metabolism
17.
Sci Rep ; 14(1): 12670, 2024 06 03.
Article En | MEDLINE | ID: mdl-38830883

Gelatin-methacryloyl (GelMA) is a highly adaptable biomaterial extensively utilized in skin regeneration applications. However, it is frequently imperative to enhance its physical and biological qualities by including supplementary substances in its composition. The purpose of this study was to fabricate and characterize a bi-layered GelMA-gelatin scaffold using 3D bioprinting. The upper section of the scaffold was encompassed with keratinocytes to simulate the epidermis, while the lower section included fibroblasts and HUVEC cells to mimic the dermis. A further step involved the addition of amniotic membrane extract (AME) to the scaffold in order to promote angiogenesis. The incorporation of gelatin into GelMA was found to enhance its stability and mechanical qualities. While the Alamar blue test demonstrated that a high concentration of GelMA (20%) resulted in a decrease in cell viability, the live/dead cell staining revealed that incorporation of AME increased the quantity of viable HUVECs. Further, gelatin upregulated the expression of KRT10 in keratinocytes and VIM in fibroblasts. Additionally, the histological staining results demonstrated the formation of well-defined skin layers and the creation of extracellular matrix (ECM) in GelMA/gelatin hydrogels during a 14-day culture period. Our study showed that a 3D-bioprinted composite scaffold comprising GelMA, gelatin, and AME can be used to regenerate skin tissues.


Amnion , Bioprinting , Fibroblasts , Gelatin , Human Umbilical Vein Endothelial Cells , Keratinocytes , Tissue Engineering , Tissue Scaffolds , Keratinocytes/drug effects , Keratinocytes/cytology , Keratinocytes/metabolism , Gelatin/chemistry , Humans , Tissue Engineering/methods , Fibroblasts/drug effects , Fibroblasts/metabolism , Fibroblasts/cytology , Tissue Scaffolds/chemistry , Amnion/cytology , Amnion/metabolism , Amnion/chemistry , Bioprinting/methods , Printing, Three-Dimensional , Skin/metabolism , Skin/cytology , Methacrylates/chemistry , Cell Survival/drug effects , Endothelial Cells/metabolism , Endothelial Cells/drug effects , Endothelial Cells/cytology
18.
Zhongguo Yi Liao Qi Xie Za Zhi ; 48(3): 245-250, 2024 May 30.
Article Zh | MEDLINE | ID: mdl-38863088

Objective: This study analyzes the risk points in the quality control of bioink and the main processes of bioprinting, clarifies and explores the quality control and supervision model for bioprinting medical devices, and provides theoretical and practical guidance to ensure the safety and effectiveness of bioprinting medical devices. Methods: The quality control risk points throughout the bioprinting process were comprehensively analyzed, with a particular focus on bioprinting materials and key processes. The regulatory model and methods for bioprinting medical devices were examined. This research concentrated on critical technologies such as extrusion, laser-assisted, and in situ bioprinting, assessing their potential for clinical applications and regulatory challenges. Results: Bioink from different sources should meet regulatory requirements. It is essential to ensure aseptic handling of raw materials and to validate sterilization under "worst-case" conditions. Conclusion: As bioprinting technology advances rapidly, corresponding research into materials, processes, and quality risk control should be conducted to ensure the concurrent development of the regulatory system. This will continuously contribute to the orderly progression of the entire industry and human health.


Bioprinting , Quality Control , Equipment and Supplies , Humans , Printing, Three-Dimensional , Tissue Engineering
19.
Int J Nanomedicine ; 19: 5459-5478, 2024.
Article En | MEDLINE | ID: mdl-38863648

Graphene family nanomaterials (GFNs) have attracted considerable attention in diverse fields from engineering and electronics to biomedical applications because of their distinctive physicochemical properties such as large specific surface area, high mechanical strength, and favorable hydrophilic nature. Moreover, GFNs have demonstrated the ability to create an anti-inflammatory environment and exhibit antibacterial effects. Consequently, these materials hold immense potential in facilitating cell adhesion, proliferation, and differentiation, further promoting the repair and regeneration of various tissues, including bone, nerve, oral, myocardial, and vascular tissues. Note that challenges still persist in current applications, including concerns regarding biosecurity risks, inadequate adhesion performance, and unsuitable degradability as matrix materials. This review provides a comprehensive overview of current advancements in the utilization of GFNs in regenerative medicine, as well as their molecular mechanism and signaling targets in facilitating tissue repair and regeneration. Future research prospects for GFNs, such as potential in promoting ocular tissue regeneration, are also discussed in details. We hope to offer a valuable reference for the clinical application of GFNs in the treatment of bone defects, nerve damage, periodontitis, and atherosclerosis.


Graphite , Nanostructures , Regenerative Medicine , Tissue Engineering , Humans , Regenerative Medicine/methods , Graphite/chemistry , Nanostructures/chemistry , Tissue Engineering/methods , Animals
20.
Biotechnol J ; 19(6): e2300570, 2024 Jun.
Article En | MEDLINE | ID: mdl-38864387

This article primarily introduces a new treatment for liver fibrosis/cirrhosis. We developed a hepatic patch by combining decellularized liver matrix (DLM) with the hepatocyte growth factor (HGF)/heparin-complex and evaluated its restorative efficacy. In vitro prophylactic results, the HGF/heparin-DLM patches effectively mitigated CCl4-induced hepatocyte toxicity and restored the cytotoxicity levels to the baseline levels by day 5. Furthermore, these patches restored albumin synthesis of injured hepatocytes to more than 70% of the normal levels within 5 days. In vitro therapeutic results, the urea synthesis of the injured hepatocytes reached 91% of the normal levels after 10 days of culture, indicating successful restoration of hepatic function by the HGF/heparin-DLM patches in both prophylactic and therapeutic models. In vivo results, HGF/heparin-DLM patches attached to the liver and gut exhibited a significant decrease in collagen content (4.44 times and 2.77 times, respectively) and an increase in glycogen content (1.19 times and 1.12 times, respectively) compared to the fibrosis group after 1 week, separately. In summary, liver function was restored and inflammation was inhibited through the combined effects of DLM and the HGF/heparin-complex in fibrotic liver. The newly designed hepatic patch holds promise for both in vitro and in vivo regeneration therapy and preventive health care for liver tissue engineering.


Carbon Tetrachloride , Heparin , Hepatocyte Growth Factor , Hepatocytes , Liver , Animals , Carbon Tetrachloride/toxicity , Hepatocyte Growth Factor/metabolism , Heparin/chemistry , Hepatocytes/drug effects , Male , Extracellular Matrix/metabolism , Extracellular Matrix/chemistry , Tissue Engineering/methods , Mice , Rats , Liver Cirrhosis/therapy , Chemical and Drug Induced Liver Injury/metabolism , Humans , Tissue Scaffolds/chemistry , Rats, Sprague-Dawley
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