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1.
ACS Appl Bio Mater ; 7(7): 4747-4759, 2024 Jul 15.
Article in English | MEDLINE | ID: mdl-39005189

ABSTRACT

Current engineered synthetic scaffolds fail to functionally repair and regenerate ruptured native tendon tissues, partly because they cannot satisfy both the unique biological and biomechanical properties of these tissues. Ideal scaffolds for tendon repair and regeneration need to provide porous topographic structures and biological cues necessary for the efficient infiltration and tenogenic differentiation of embedded stem cells. To obtain crimped and porous scaffolds, highly aligned poly(l-lactide) fibers were prepared by electrospinning followed by postprocessing. Through a mild and controlled hydrogen gas foaming technique, we successfully transformed the crimped fibrous mats into three-dimensional porous scaffolds without sacrificing the crimped microstructure. Porcine derived decellularized tendon matrix was then grafted onto this porous scaffold through fiber surface modification and carbodiimide chemistry. These biofunctionalized, crimped, and porous scaffolds supported the proliferation, migration, and tenogenic induction of tendon derived stem/progenitor cells, while enabling adhesion to native tendons. Together, our data suggest that these biofunctionalized scaffolds can be exploited as promising engineered scaffolds for the treatment of acute tendon rupture.


Subject(s)
Biocompatible Materials , Materials Testing , Regeneration , Tendons , Tissue Scaffolds , Tissue Scaffolds/chemistry , Tendons/cytology , Animals , Swine , Porosity , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Tissue Engineering , Cell Proliferation/drug effects , Particle Size , Decellularized Extracellular Matrix/chemistry , Decellularized Extracellular Matrix/pharmacology , Polyesters/chemistry
2.
Acta Biomater ; 181: 202-221, 2024 06.
Article in English | MEDLINE | ID: mdl-38692468

ABSTRACT

Dental pulp is the only soft tissue in the tooth which plays a crucial role in maintaining intrinsic multi-functional behaviors of the dentin-pulp complex. Nevertheless, the restoration of fully functional pulps after pulpitis or pulp necrosis, termed endodontic regeneration, remained a major challenge for decades. Therefore, a bioactive and in-situ injectable biomaterial is highly desired for tissue-engineered pulp regeneration. Herein, a decellularized matrix hydrogel derived from porcine dental pulps (pDDPM-G) was prepared and characterized through systematic comparison against the porcine decellularized nerve matrix hydrogel (pDNM-G). The pDDPM-G not only exhibited superior capabilities in facilitating multi-directional differentiation of dental pulp stem cells (DPSCs) during 3D culture, but also promoted regeneration of pulp-like tissues after DPSCs encapsulation and transplantation. Further comparative proteomic and transcriptome analyses revealed the differential compositions and potential mechanisms that endow the pDDPM-G with highly tissue-specific properties. Finally, it was realized that the abundant tenascin C (TNC) in pDDPM served as key factor responsible for the activation of Notch signaling cascades and promoted DPSCs odontoblastic differentiation. Overall, it is believed that pDDPM-G is a sort of multi-functional and tissue-specific hydrogel-based material that holds great promise in endodontic regeneration and clinical translation. STATEMENT OF SIGNIFICANCE: Functional hydrogel-based biomaterials are highly desirable for endodontic regeneration treatments. Decellularized extracellular matrix (dECM) preserves most extracellular matrix components of its native tissue, exhibiting unique advantages in promoting tissue regeneration and functional restoration. In this study, we prepared a porcine dental pulp-derived dECM hydrogel (pDDPM-G), which exhibited superior performance in promoting odontogenesis, angiogenesis, and neurogenesis of the regenerating pulp-like tissue, further showed its tissue-specificity compared to the peripheral nerve-derived dECM hydrogel. In-depth proteomic and transcriptomic analyses revealed that the activation of tenascin C-Notch axis played an important role in facilitating odontogenic regeneration. This biomaterial-based study validated the great potential of the dental pulp-specific pDDPM-G for clinical applications, and provides a springboard for research strategies in ECM-related regenerative medicine.


Subject(s)
Dental Pulp , Hydrogels , Regeneration , Stem Cells , Dental Pulp/cytology , Animals , Hydrogels/chemistry , Swine , Regeneration/drug effects , Stem Cells/cytology , Stem Cells/metabolism , Decellularized Extracellular Matrix/chemistry , Decellularized Extracellular Matrix/pharmacology , Cell Differentiation/drug effects , Regenerative Endodontics/methods , Humans , Tissue Engineering/methods
3.
Cell Biochem Funct ; 42(4): e4038, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38736214

ABSTRACT

The generation of insulin-producing cells (IPCs) is an attractive approach for replacing damaged ß cells in diabetic patients. In the present work, we introduced a hybrid platform of decellularized amniotic membrane (dAM) and fibrin encapsulation for differentiating adipose tissue-derived stem cells (ASCs) into IPCs. ASCs were isolated from healthy donors and characterized. Human AM was decellularized, and its morphology, DNA, collagen, glycosaminoglycan (GAG) contents, and biocompatibility were evaluated. ASCs were subjected to four IPC differentiation methods, and the most efficient method was selected for the experiment. ASCs were seeded onto dAM, alone or encapsulated in fibrin gel with various thrombin concentrations, and differentiated into IPCs according to a method applying serum-free media containing 2-mercaptoethanol, nicotinamide, and exendin-4. PDX-1, GLUT-2 and insulin expression were evaluated in differentiated cells using real-time PCR. Structural integrity and collagen and GAG contents of AM were preserved after decellularization, while DNA content was minimized. Cultivating ASCs on dAM augmented their attachment, proliferation, and viability and enhanced the expression of PDX-1, GLUT-2, and insulin in differentiated cells. Encapsulating ASCs in fibrin gel containing 2 mg/ml fibrinogen and 10 units/ml thrombin increased their differentiation into IPCs. dAM and fibrin gel synergistically enhanced the differentiation of ASCs into IPCs, which could be considered an appropriate strategy for replacing damaged ß cells.


Subject(s)
Adipose Tissue , Cell Differentiation , Fibrin , Insulin , Stem Cells , Humans , Cell Differentiation/drug effects , Fibrin/chemistry , Fibrin/metabolism , Adipose Tissue/cytology , Adipose Tissue/metabolism , Stem Cells/metabolism , Stem Cells/cytology , Insulin/metabolism , Cells, Cultured , Insulin-Secreting Cells/metabolism , Insulin-Secreting Cells/cytology , Decellularized Extracellular Matrix/chemistry , Decellularized Extracellular Matrix/metabolism , Decellularized Extracellular Matrix/pharmacology , Amnion/cytology , Amnion/metabolism , Amnion/chemistry
4.
Biomater Adv ; 161: 213883, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38762928

ABSTRACT

Maintaining the viability of damaged pulp is critical in clinical dentistry. Pulp capping, by placing dental material over the exposed pulp, is a main approach to promote pulp-dentin healing and mineralized tissue formation. The dental materials are desired to impact on intricate physiological mechanisms in the healing process, including early regulation of inflammation, immunity, and cellular events. In this study, we developed an injectable dental pulp-derived decellularized matrix (DPM) hydrogel to modulate macrophage responses and promote dentin repair. The DPM derived from porcine dental pulp has high collagen retention and low DNA content. The DPM was solubilized by pepsin digestion (named p-DPM) and subsequently injected through a 25G needle to form hydrogel facilely at 37 °C. In vitro results demonstrated that the p-DPM induced the M2-polarization of macrophages and the migration, proliferation, and dentin differentiation of human dental pulp stem cells from deciduous teeth (SHEDs). In a mouse subcutaneous injection test, the p-DPM hydrogel was found to facilitate cell recruitment and M2 polarization during the early phase of implantation. Additionally, the acute pulp restoration in rat models proved that injectable p-DPM hydrogel as a pulp-capping agent had excellent efficacy in dentin regeneration. This study demonstrates that the DPM promotes dentin repair by modulating macrophage responses, and has a potential for pulp-capping applications in dental practice.


Subject(s)
Dental Pulp , Dentin , Hydrogels , Macrophages , Dental Pulp/cytology , Dental Pulp/drug effects , Animals , Macrophages/drug effects , Macrophages/metabolism , Humans , Dentin/drug effects , Dentin/chemistry , Hydrogels/chemistry , Mice , Rats , Decellularized Extracellular Matrix/chemistry , Decellularized Extracellular Matrix/pharmacology , Swine , Cell Differentiation/drug effects , Regeneration/drug effects , Cell Proliferation/drug effects , Stem Cells/drug effects , Stem Cells/cytology , Wound Healing/drug effects
5.
J Mater Chem B ; 12(22): 5513-5524, 2024 Jun 05.
Article in English | MEDLINE | ID: mdl-38745541

ABSTRACT

BACKGROUND: In the domain of plastic surgery, nasal cartilage regeneration is of significant importance. The extracellular matrix (ECM) from porcine nasal septum cartilage has shown potential for promoting human cartilage regeneration. Nonetheless, the specific biological inductive factors and their pathways in cartilage tissue engineering remain undefined. METHODS: The decellularized matrix derived from porcine nasal septum cartilage (PN-DCM) was prepared using a grinding method. Human umbilical cord mesenchymal stem cells (HuMSCs) were cultured on these PN-DCM scaffolds for 4 weeks without exogenous growth factors to evaluate their chondroinductive potential. Subsequently, proteomic analysis was employed to identify potential biological inductive factors within the PN-DCM scaffolds. RESULTS: Compared to the TGF-ß3-cultured pellet model serving as a positive control, the PN-DCM scaffolds promoted significant deposition of a Safranin-O positive matrix and Type II collagen by HuMSCs. Gene expression profiling revealed upregulation of ACAN, COL2A1, and SOX9. Proteomic analysis identified potential chondroinductive factors in the PN-DCM scaffolds, including CYTL1, CTGF, MGP, ITGB1, BMP7, and GDF5, which influence HuMSC differentiation. CONCLUSION: Our findings have demonstrated that the PN-DCM scaffolds promoted HuMSC differentiation towards a nasal chondrocyte phenotype without the supplementation of exogenous growth factors. This outcome is associated with the chondroinductive factors present within the PN-DCM scaffolds.


Subject(s)
Cell Differentiation , Chondrogenesis , Mesenchymal Stem Cells , Nasal Septum , Humans , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/metabolism , Nasal Septum/cytology , Nasal Septum/chemistry , Animals , Swine , Cells, Cultured , Tissue Scaffolds/chemistry , Decellularized Extracellular Matrix/chemistry , Decellularized Extracellular Matrix/pharmacology , Extracellular Matrix/metabolism , Extracellular Matrix/chemistry , Tissue Engineering , Umbilical Cord/cytology
6.
Biofabrication ; 16(3)2024 May 07.
Article in English | MEDLINE | ID: mdl-38663394

ABSTRACT

Extracellular matrix (ECM) rich whole organ bio-scaffolds, preserving structural integrity and essential growth factors, has potential towards regeneration and reconstruction. Women with cervical anomalies or trauma can benefit from clinical cervicovaginal repair using constructs rich in site specific ECM. In this study, complete human cervix decellularization was achieved using a modified perfusion-based stir bench top decellularization method. This was followed by physico-chemical processes including perfusion of ionic agents, enzymatic treatment and washing using detergent solutions for a duration of 10-12 d. Histopathological analysis, as well as DNA quantification confirmed the efficacy of the decellularization process. Tissue ultrastructure integrity was preserved and the same was validated via scanning electron microscopy and transmission electron microscopy studies. Biochemical analysis and structural characterizations like Fourier transform infrared, Raman spectroscopy of decellularized tissues demonstrated preservation of important proteins, crucial growth factors, collagen, and glycosaminoglycans.In vitrostudies, using THP-1 and human umbilical vein endothelial cell (HUVEC) cells, demonstrated macrophage polarization from M1 to M2 and vascular functional genes enhancement, respectively, when treated with decellularized human cervical matrix (DHCp). Crosslinked DHC scaffolds were recellularized with site specific human cervical epithelial cells and HUVEC, showing non-cytotoxic cell viability and enhanced proliferation. Furthermore, DHC scaffolds showed immunomodulatory effectsin vivoon small rodent model via upregulation of M2 macrophage genes as compared to decellularized rat cervix matrix scaffolds (DRC). DHC scaffolds underwent neo-vascularization followed by ECM remodeling with enhanced tissue integration.


Subject(s)
Cervix Uteri , Decellularized Extracellular Matrix , Human Umbilical Vein Endothelial Cells , Tissue Scaffolds , Humans , Female , Cervix Uteri/cytology , Animals , Decellularized Extracellular Matrix/chemistry , Decellularized Extracellular Matrix/pharmacology , Tissue Scaffolds/chemistry , Extracellular Matrix/metabolism , Extracellular Matrix/chemistry , Rats , Tissue Engineering , THP-1 Cells , Macrophages/metabolism , Macrophages/cytology , Rats, Sprague-Dawley
7.
Acta Biomater ; 180: 295-307, 2024 05.
Article in English | MEDLINE | ID: mdl-38642787

ABSTRACT

Kidney regeneration is hindered by the limited pool of intrinsic reparative cells. Advanced therapies targeting renal regeneration have the potential to alleviate the clinical and financial burdens associated with kidney disease. Delivery systems for cells, extracellular vesicles, or growth factors aimed at enhancing regeneration can benefit from vehicles enabling targeted delivery and controlled release. Hydrogels, optimized to carry biological cargo while promoting regeneration, have emerged as promising candidates for this purpose. This study aims to develop a hydrogel from decellularized kidney extracellular matrix (DKECM) and explore its biocompatibility as a biomaterial for renal regeneration. The resulting hydrogel crosslinks with temperature and exhibits a high concentration of extracellular matrix. The decellularization process efficiently removes detergent residues, yielding a pathogen-free biomaterial that is non-hemolytic and devoid of α-gal epitope. Upon interaction with macrophages, the hydrogel induces differentiation into both pro-inflammatory and anti-inflammatory phenotypes, suggesting an adequate balance to promote biomaterial functionality in vivo. Renal progenitor cells encapsulated in the DKECM hydrogel demonstrate higher viability and proliferation than in commercial collagen-I hydrogels, while also expressing tubular cells and podocyte markers in long-term culture. Overall, the injectable biomaterial derived from porcine DKECM is anticipated to elicit minimal host reaction while fostering progenitor cell bioactivity, offering a potential avenue for enhancing renal regeneration in clinical settings. STATEMENT OF SIGNIFICANCE: The quest to improve treatments for kidney disease is crucial, given the challenges faced by patients on dialysis or waiting for transplants. Exciting new therapies combining biomaterials with cells can revolutionize kidney repair. In this study, researchers created a hydrogel from pig kidney. This gel could be used to deliver cells and other substances that help in kidney regeneration. Despite coming from pigs, it's safe for use in humans, with no harmful substances and reduced risk of immune reactions. Importantly, it promotes a balanced healing response in the body. This research not only advances our knowledge of kidney repair but also offers hope for more effective treatments for kidney diseases.


Subject(s)
Decellularized Extracellular Matrix , Hydrogels , Kidney , Tissue Engineering , Hydrogels/chemistry , Animals , Tissue Engineering/methods , Decellularized Extracellular Matrix/chemistry , Decellularized Extracellular Matrix/pharmacology , Swine , Extracellular Matrix/chemistry , Humans , Stem Cells/cytology , Stem Cells/metabolism , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology
8.
ACS Biomater Sci Eng ; 10(5): 3203-3217, 2024 05 13.
Article in English | MEDLINE | ID: mdl-38557027

ABSTRACT

The intricate electrophysiological functions and anatomical structures of spinal cord tissue render the establishment of in vitro models for spinal cord-related diseases highly challenging. Currently, both in vivo and in vitro models for spinal cord-related diseases are still underdeveloped, complicating the exploration and development of effective therapeutic drugs or strategies. Organoids cultured from human induced pluripotent stem cells (hiPSCs) hold promise as suitable in vitro models for spinal cord-related diseases. However, the cultivation of spinal cord organoids predominantly relies on Matrigel, a matrix derived from murine sarcoma tissue. Tissue-specific extracellular matrices are key drivers of complex organ development, thus underscoring the urgent need to research safer and more physiologically relevant organoid culture materials. Herein, we have prepared a rat decellularized brain extracellular matrix hydrogel (DBECMH), which supports the formation of hiPSC-derived spinal cord organoids. Compared with Matrigel, organoids cultured in DBECMH exhibited higher expression levels of markers from multiple compartments of the natural spinal cord, facilitating the development and maturation of spinal cord organoid tissues. Our study suggests that DBECMH holds potential to replace Matrigel as the standard culture medium for human spinal cord organoids, thereby advancing the development of spinal cord organoid culture protocols and their application in in vitro modeling of spinal cord-related diseases.


Subject(s)
Brain , Hydrogels , Induced Pluripotent Stem Cells , Organoids , Spinal Cord , Organoids/drug effects , Organoids/cytology , Organoids/metabolism , Humans , Animals , Spinal Cord/cytology , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/drug effects , Hydrogels/chemistry , Hydrogels/pharmacology , Brain/metabolism , Rats , Decellularized Extracellular Matrix/chemistry , Decellularized Extracellular Matrix/pharmacology , Extracellular Matrix/metabolism , Extracellular Matrix/chemistry , Laminin/pharmacology , Laminin/chemistry , Proteoglycans/chemistry , Rats, Sprague-Dawley , Drug Combinations , Collagen
9.
ACS Biomater Sci Eng ; 10(5): 3218-3231, 2024 05 13.
Article in English | MEDLINE | ID: mdl-38593429

ABSTRACT

Spinal cord organoids are of significant value in the research of spinal cord-related diseases by simulating disease states, thereby facilitating the development of novel therapies. However, the complexity of spinal cord structure and physiological functions, along with the lack of human-derived inducing components, presents challenges in the in vitro construction of human spinal cord organoids. Here, we introduce a novel human decellularized placenta-derived extracellular matrix hydrogel (DPECMH) and, combined with a new induction protocol, successfully construct human spinal cord organoids. The human placenta-sourced decellularized extracellular matrix (dECM), verified through hematoxylin and eosin staining, DNA quantification, and immunofluorescence staining, retained essential ECM components such as elastin, fibronectin, type I collagen, laminin, and so forth. The temperature-sensitive hydrogel made from human placenta dECM demonstrated good biocompatibility and promoted the differentiation of human induced pluripotent stem cell (hiPSCs)-derived spinal cord organoids into neurons. It displayed enhanced expression of laminar markers in comparison to Matrigel and showed higher expression of laminar markers compared to Matrigel, accelerating the maturation process of spinal cord organoids and demonstrating its potential as an organoid culture substrate. DPECMH has the potential to replace Matrigel as the standard additive for human spinal cord organoids, thus advancing the development of spinal cord organoid culture protocols and their application in the in vitro modeling of spinal cord-related diseases.


Subject(s)
Cell Differentiation , Decellularized Extracellular Matrix , Hydrogels , Induced Pluripotent Stem Cells , Organoids , Placenta , Spinal Cord , Humans , Organoids/cytology , Organoids/metabolism , Organoids/drug effects , Female , Placenta/cytology , Induced Pluripotent Stem Cells/cytology , Induced Pluripotent Stem Cells/drug effects , Induced Pluripotent Stem Cells/metabolism , Pregnancy , Hydrogels/chemistry , Hydrogels/pharmacology , Spinal Cord/cytology , Spinal Cord/metabolism , Cell Differentiation/drug effects , Decellularized Extracellular Matrix/pharmacology , Decellularized Extracellular Matrix/chemistry , Extracellular Matrix/metabolism , Extracellular Matrix/chemistry , Laminin/pharmacology , Laminin/chemistry
10.
Adv Healthc Mater ; 13(16): e2303737, 2024 06.
Article in English | MEDLINE | ID: mdl-38560921

ABSTRACT

Tissue engineering heart valves (TEHVs) are expected to address the limitations of mechanical and bioprosthetic valves used in clinical practice. Decellularized heart valve (DHV) is an important scaffold of TEHVs due to its natural three-dimensional structure and bioactive extracellular matrix, but its mechanical properties and hemocompatibility are impaired. In this study, DHV is cross-linked with three different molecular weights of oxidized hyaluronic acid (OHA) by a Schiff base reaction and presented enhanced stability and hemocompatibility, which could be mediated by the molecular weight of OHA. Notably, DHV cross-linked with middle- and high-molecular-weight OHA could drive the macrophage polarization toward the M2 phenotype in vitro. Moreover, DHV cross-linked with middle-molecular-weight OHA scaffolds are further modified with RGD-PHSRN peptide (RPF-OHA/DHV) to block the residual aldehyde groups of the unreacted OHA. The results show that RPF-OHA/DHV not only exhibits anti-calcification properties, but also facilitates endothelial cell adhesion and proliferation in vitro. Furthermore, RPF-OHA/DHV shows excellent performance under an in vivo hemodynamic environment with favorable recellularization and immune regulation without calcification. The optimistic results demonstrate that OHA with different molecular weights has different cross-linking effects on DHV and that RPF-OHA/DHV scaffold with enhanced immune regulation, anti-calcification, and recellularization properties for clinical transformation.


Subject(s)
Hyaluronic Acid , Tissue Engineering , Hyaluronic Acid/chemistry , Hyaluronic Acid/pharmacology , Animals , Tissue Engineering/methods , Humans , Heart Valves , Tissue Scaffolds/chemistry , Immunomodulation/drug effects , Oxidation-Reduction/drug effects , Mice , Calcinosis , Macrophages/drug effects , Macrophages/metabolism , Macrophages/immunology , Decellularized Extracellular Matrix/chemistry , Decellularized Extracellular Matrix/pharmacology , Heart Valve Prosthesis , Cell Proliferation/drug effects , Human Umbilical Vein Endothelial Cells/metabolism , Cell Adhesion/drug effects
11.
Cells ; 13(8)2024 Apr 16.
Article in English | MEDLINE | ID: mdl-38667303

ABSTRACT

Skeletal muscle degeneration is responsible for major mobility complications, and this muscle type has little regenerative capacity. Several biomaterials have been proposed to induce muscle regeneration and function restoration. Decellularized scaffolds present biological properties that allow efficient cell culture, providing a suitable microenvironment for artificial construct development and being an alternative for in vitro muscle culture. For translational purposes, biomaterials derived from large animals are an interesting and unexplored source for muscle scaffold production. Therefore, this study aimed to produce and characterize bovine muscle scaffolds to be applied to muscle cell 3D cultures. Bovine muscle fragments were immersed in decellularizing solutions for 7 days. Decellularization efficiency, structure, composition, and three-dimensionality were evaluated. Bovine fetal myoblasts were cultured on the scaffolds for 10 days to attest cytocompatibility. Decellularization was confirmed by DAPI staining and DNA quantification. Histological and immunohistochemical analysis attested to the preservation of main ECM components. SEM analysis demonstrated that the 3D structure was maintained. In addition, after 10 days, fetal myoblasts were able to adhere and proliferate on the scaffolds, attesting to their cytocompatibility. These data, even preliminary, infer that generated bovine muscular scaffolds were well structured, with preserved composition and allowed cell culture. This study demonstrated that biomaterials derived from bovine muscle could be used in tissue engineering.


Subject(s)
Muscle, Skeletal , Myoblasts , Tissue Engineering , Tissue Scaffolds , Animals , Cattle , Tissue Scaffolds/chemistry , Muscle, Skeletal/cytology , Tissue Engineering/methods , Myoblasts/cytology , Biocompatible Materials/chemistry , Decellularized Extracellular Matrix/chemistry , Decellularized Extracellular Matrix/pharmacology , Cells, Cultured , Cell Proliferation , Extracellular Matrix/metabolism
12.
Cardiovasc Eng Technol ; 15(3): 279-289, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38347340

ABSTRACT

PURPOSE: This study aims to decellularized caprine pericardium tissue with varied non-ionic surfactant and anionic detergent concentrations. METHODS: Protocol A consists of 1%, 0.5%, and 0.25% (w/v) sodium dodecyl sulphate (SDS). Protocol B uses 1%, 0.5%, and 0.25% (w/v) Triton X-100. Protocol C comprised 0.5% SDS + 0.5% Triton X-100, 0.5% + 0.25%, and 0.25% SDS + 0.5% Triton X-100. RESULTS: Protocol B left a few countable cells in the pericardium tissue, but treatments A and C removed all cells. DNA quantification also demonstrated that protocol B had the most leftover DNA after decellularization. The pericardium tissue treated with an equal combination of anionic detergent and non-ionic surfactant preserves the matrix. However, changing the anionic detergent-non-ionic surfactant ratio disrupted the microstructure. Protocol A decreased pericardium tissue secant modulus (p < 0.05). Protocol B-treated pericardium tissue matched native tissue secant modulus and ultimate tensile stress. Protocol C strengthened pericardium tissue. CONCLUSION: The intact extracellular matrix and biomechanical properties like native tissues require optimal chemical doses and combinations.


Subject(s)
Goats , Octoxynol , Pericardium , Sodium Dodecyl Sulfate , Pericardium/drug effects , Pericardium/cytology , Animals , Octoxynol/pharmacology , Octoxynol/chemistry , Sodium Dodecyl Sulfate/pharmacology , Decellularized Extracellular Matrix/chemistry , Decellularized Extracellular Matrix/pharmacology , Detergents , Surface-Active Agents/chemistry , Surface-Active Agents/pharmacology , DNA , Biomechanical Phenomena , Elastic Modulus
13.
Macromol Biosci ; 24(5): e2300411, 2024 May.
Article in English | MEDLINE | ID: mdl-38326219

ABSTRACT

Liver fibrosis occurs in many chronic liver diseases, while severe fibrosis can lead to liver failure. A chitosan-phenol based self-healing hydrogel (CP) integrated with decellularized liver matrix (DLM) is proposed in this study as a 3D gel matrix to carry hepatocytes for possible therapy of liver fibrosis. To mimic the physiological liver microenvironment, DLM is extracted from pigs and mixed with CP hydrogel to generate DLM-CP self-healing hydrogel. Hepatocyte spheroids coated with endothelial cells (ECs) are fabricated using a customized method and embedded in the hydrogel. Hepatocytes injured by exposure to CCl4-containing medium are used as the in vitro toxin-mediated liver fibrosis model, where the EC-covered hepatocyte spheroids embedded in the hydrogel are co-cultured with the injured hepatocytes. The urea synthesis of the injured hepatocytes reaches 91% of the normal level after 7 days of co-culture, indicating that the hepatic function of injured hepatocytes is rescued by the hybrid spheroid-laden DLM-CP hydrogel. Moreover, the relative lactate dehydrogenase activity of the injured hepatocytes is decreased 49% by the hybrid spheroid-laden DLM-CP hydrogel after 7 days of co-culture, suggesting reduced damage in the injured hepatocytes. The combination of hepatocyte/EC hybrid spheroids and DLM-CP hydrogel presents a promising therapeutic strategy for hepatic fibrosis.


Subject(s)
Coculture Techniques , Endothelial Cells , Hepatocytes , Hydrogels , Liver , Spheroids, Cellular , Hepatocytes/metabolism , Hepatocytes/cytology , Animals , Spheroids, Cellular/cytology , Hydrogels/chemistry , Hydrogels/pharmacology , Endothelial Cells/cytology , Endothelial Cells/metabolism , Liver/injuries , Liver/pathology , Swine , Decellularized Extracellular Matrix/chemistry , Decellularized Extracellular Matrix/pharmacology , Chitosan/chemistry , Chitosan/pharmacology , Humans , Liver Cirrhosis/pathology , Liver Cirrhosis/therapy , Extracellular Matrix/metabolism , Carbon Tetrachloride
14.
ACS Appl Mater Interfaces ; 15(2): 2578-2589, 2023 Jan 18.
Article in English | MEDLINE | ID: mdl-36598791

ABSTRACT

Transplantation of exogenous cardiomyocytes (CMs) is a hopeful method to treat myocardial infarction (MI). However, its clinical application still remains challenging due to low retention and survival rates of the transplanted cells. Herein, a stromal cell-derived factor 1 (SDF-1)-loaded injectable hydrogel based on a decellularized porcine extracellular matrix (dECM) is developed to encapsulate and deliver CMs locally to the infarct area of the heart. The soluble porcine cardiac dECM is composed of similar components such as the human cardiac ECM, which could be self-assembled into a nanofibrous hydrogel at physiological temperature to improve the retention of transplanted CMs. Furthermore, the chemokine SDF-1 could recruit endogenous cells to promote angiogenesis, mitigating the ischemic microenvironment and improving the survival of CMs. The results in vitro show that this composite hydrogel exhibits good biocompatibility, anti-apoptosis property, and chemotactic effects for mesenchymal stromal cells and endothelial cells through SDF-1-CXCR4 axis. Moreover, intramyocardial injection of this composite hydrogel to the infarcted area leads to the promotion of angiogenesis and inhibition of fibrosis, reducing the infarction size and improving the cardiac function. The combination of natural biomaterials, exogenous cells, and bioactive factors shows potential for MI treatment in the clinical application.


Subject(s)
Chemokine CXCL12 , Decellularized Extracellular Matrix , Hydrogels , Myocardial Infarction , Myocytes, Cardiac , Animals , Humans , Chemokine CXCL12/chemistry , Chemokine CXCL12/pharmacology , Decellularized Extracellular Matrix/chemistry , Decellularized Extracellular Matrix/pharmacology , Endothelial Cells , Extracellular Matrix , Hydrogels/pharmacology , Myocardial Infarction/therapy , Myocytes, Cardiac/metabolism , Regeneration , Swine
15.
Biomed Mater ; 17(2)2022 02 02.
Article in English | MEDLINE | ID: mdl-35026740

ABSTRACT

The design of bone scaffolds is predominately aimed to well reproduce the natural bony environment by imitating the architecture/composition of host bone. Such biomimetic biomaterials are gaining increasing attention and acknowledged quite promising for bone tissue engineering. Herein, novel biomimetic bone scaffolds containing decellularized small intestinal submucosa matrix (SIS-ECM) and Sr2+/Fe3+co-doped hydroxyapatite (SrFeHA) are fabricated for the first time by the sophisticated self-assembled mineralization procedure, followed by cross-linking and lyophilization post-treatments. The results indicate the constructed SIS/SrFeHA scaffolds are characterized by highly porous structures, rough microsurface and improved mechanical strength, as well as efficient releasing of bioactive Sr2+/Fe3+and ECM components. These favorable physico-chemical properties endow SIS/SrFeHA scaffolds with an architectural/componential biomimetic bony environment which appears to be highly beneficial for inducing angiogenesis/osteogenesis bothin vitroandin vivo. In particular, the cellular functionality and bioactivity of endotheliocytes/osteoblasts are significantly enhanced by SIS/SrFeHA scaffolds, and the cranial defects model further verifies the potent ability of SIS/SrFeHA to acceleratein vivovascularization and bone regeneration following implantation. In this view these results highlight the considerable angiogenesis/osteogenesis potential of biomimetic porous SIS/SrFeHA scaffolds for inducing bone regeneration and thus may afford a new promising alternative for bone tissue engineering.


Subject(s)
Bone Regeneration/drug effects , Decellularized Extracellular Matrix , Durapatite , Osteogenesis/drug effects , Tissue Scaffolds/chemistry , Animals , Biomimetic Materials , Cell Line , Cells, Cultured , Decellularized Extracellular Matrix/chemistry , Decellularized Extracellular Matrix/pharmacology , Durapatite/chemistry , Durapatite/pharmacology , Human Umbilical Vein Endothelial Cells , Humans , Intestinal Mucosa/cytology , Intestine, Small/cytology , Mice , Neovascularization, Physiologic/drug effects , Osteoblasts/drug effects , Porosity
16.
J Nanobiotechnology ; 20(1): 25, 2022 Jan 06.
Article in English | MEDLINE | ID: mdl-34991615

ABSTRACT

BACKGROUND: The regeneration and repair of articular cartilage remains a major challenge for clinicians and scientists due to the poor intrinsic healing of this tissue. Since cartilage injuries are often clinically irregular, tissue-engineered scaffolds that can be easily molded to fill cartilage defects of any shape that fit tightly into the host cartilage are needed. METHOD: In this study, bone marrow mesenchymal stem cell (BMSC) affinity peptide sequence PFSSTKT (PFS)-modified chondrocyte extracellular matrix (ECM) particles combined with GelMA hydrogel were constructed. RESULTS: In vitro experiments showed that the pore size and porosity of the solid-supported composite scaffolds were appropriate and that the scaffolds provided a three-dimensional microenvironment supporting cell adhesion, proliferation and chondrogenic differentiation. In vitro experiments also showed that GelMA/ECM-PFS could regulate the migration of rabbit BMSCs. Two weeks after implantation in vivo, the GelMA/ECM-PFS functional scaffold system promoted the recruitment of endogenous mesenchymal stem cells from the defect site. GelMA/ECM-PFS achieved successful hyaline cartilage repair in rabbits in vivo, while the control treatment mostly resulted in fibrous tissue repair. CONCLUSION: This combination of endogenous cell recruitment and chondrogenesis is an ideal strategy for repairing irregular cartilage defects.


Subject(s)
Chondrogenesis/drug effects , Decellularized Extracellular Matrix , Hydrogels , Oligopeptides , Tissue Scaffolds/chemistry , Animals , Cartilage, Articular/cytology , Decellularized Extracellular Matrix/chemistry , Decellularized Extracellular Matrix/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Male , Mesenchymal Stem Cells/drug effects , Oligopeptides/chemistry , Oligopeptides/pharmacology , Rabbits , Tissue Engineering/methods
17.
Int J Mol Sci ; 22(24)2021 Dec 15.
Article in English | MEDLINE | ID: mdl-34948251

ABSTRACT

An approach called cell-free therapy has rapidly developed in regenerative medicine over the past decade. Understanding the molecular mechanisms and signaling pathways involved in the internal potential of tissue repair inspires the development of new strategies aimed at controlling and enhancing these processes during regeneration. The use of stem cell mobilization, or homing for regeneration based on endogenous healing mechanisms, prompted a new concept in regenerative medicine: endogenous regenerative medicine. The application of cell-free therapeutic agents leading to the recruitment/homing of endogenous stem cells has advantages in overcoming the limitations and risks associated with cell therapy. In this review, we discuss the potential of cell-free products such as the decellularized extracellular matrix, growth factors, extracellular vesicles and miRNAs in endogenous bone and dental regeneration.


Subject(s)
Guided Tissue Regeneration/trends , Regenerative Medicine/methods , Regenerative Medicine/trends , Animals , Bone Regeneration/physiology , Bone and Bones/physiology , Cell- and Tissue-Based Therapy/methods , Cell- and Tissue-Based Therapy/trends , Decellularized Extracellular Matrix/pharmacology , Extracellular Vesicles/physiology , Guided Tissue Regeneration/methods , Humans , Intercellular Signaling Peptides and Proteins/pharmacology , MicroRNAs/therapeutic use , Stem Cells , Tissue Engineering , Tooth/physiology , Wound Healing
18.
Commun Biol ; 4(1): 1387, 2021 12 10.
Article in English | MEDLINE | ID: mdl-34893703

ABSTRACT

Organoids-cellular aggregates derived from stem or progenitor cells that recapitulate organ function in miniature-are of growing interest in developmental biology and medicine. Organoids have been developed for organs and tissues such as the liver, gut, brain, and pancreas; they are used as organ surrogates to study a wide range of questions in basic and developmental biology, genetic disorders, and therapies. However, many organoids reported to date have been cultured in Matrigel, which is prepared from the secretion of Engelbreth-Holm-Swarm mouse sarcoma cells; Matrigel is complex and poorly defined. This complexity makes it difficult to elucidate Matrigel-specific factors governing organoid development. In this review, we discuss promising Matrigel-free methods for the generation and maintenance of organoids that use decellularized extracellular matrix (ECM), synthetic hydrogels, or gel-forming recombinant proteins.


Subject(s)
Biocompatible Materials/pharmacology , Collagen/pharmacology , Decellularized Extracellular Matrix/pharmacology , Hydrogels/pharmacology , Laminin/pharmacology , Organoids/metabolism , Proteoglycans/pharmacology , Tissue Culture Techniques/methods , Animals , Drug Combinations , Humans , Mice
19.
Int J Mol Sci ; 22(22)2021 Nov 22.
Article in English | MEDLINE | ID: mdl-34830444

ABSTRACT

A dome-shaped elastic poly(l-lactide-co-caprolactone) (PLCL) scaffold with a channel and pore structure was fabricated by a combinative method of 3D printing technology and the gel pressing method (13 mm in diameter and 6.5 mm in thickness) for patient-specific regeneration. The PLCL scaffold was combined with adipose decellularized extracellular matrix (adECM) and heart decellularized extracellular matrix (hdECM) hydrogels and human adipose-derived stem cells (hADSCs) to promote adipogenesis and angiogenesis. These scaffolds had mechanical properties similar to those of native adipose tissue for improved tissue regeneration. The results of the in vitro real-time PCR showed that the dECM hydrogel mixture induces adipogenesis. In addition, the in vivo study at 12 weeks demonstrated that the tissue-engineered PLCL scaffolds containing the hydrogel mixture (hdECM/adECM (80:20)) and hADSCs promoted angiogenesis and adipose tissue formation, and suppressed apoptosis. Therefore, we expect that our constructs will be clinically applicable as material for the regeneration of patient-specific large-sized adipose tissue.


Subject(s)
Adipogenesis/drug effects , Adipose Tissue/growth & development , Neovascularization, Physiologic/drug effects , Regeneration/genetics , Adipose Tissue/transplantation , Animals , Apoptosis/drug effects , Decellularized Extracellular Matrix/pharmacology , Gene Expression Regulation, Developmental/drug effects , Humans , Hydrogels/chemistry , Hydrogels/pharmacology , Mesenchymal Stem Cells/cytology , Mice , Myocardium/cytology , Myocardium/metabolism , Neovascularization, Physiologic/genetics , Polyesters/pharmacology , Printing, Three-Dimensional , Regeneration/drug effects
20.
Biomed Mater ; 16(6)2021 10 04.
Article in English | MEDLINE | ID: mdl-34547733

ABSTRACT

Electrospinning represents the simplest approach to fabricate nanofiber scaffolds that approximate the heterogeneous fibrous structure of the meniscus. More effort is needed to understand the relationship between scaffold properties and cell responses to determine the appropriate scaffolds supporting meniscus tissue repair and regeneration. In this study, we investigate the influence of nanofiber configuration of electrospun scaffolds on phenotype and matrix production of meniscus cells, as well as on scaffold degradation behaviors and biocompatibility. Twisting electrospun nanofibers into yarns not only recapitulates the major collagen bundles of the meniscus but also increases the pore size and porosity of resultant scaffolds. The yarn scaffold significantly regulated expression levels of meniscus-associated genes and promoted extracellular matrix production compared with conventional electrospun scaffolds with random or aligned nanofiber orientation. Additionally, the yarn scaffold allowed considerable cell infiltration and experienced faster degradation and tissue remodeling upon subcutaneous implantation in a rat model. These results suggest that nanofiber configuration dictates cell interactions, scaffold degradation and integration with host tissue, providing design parameters of porosity and pore size of electrospun scaffolds toward meniscus repair.


Subject(s)
Decellularized Extracellular Matrix , Meniscus/cytology , Nanofibers/chemistry , Tissue Scaffolds/chemistry , Animals , Decellularized Extracellular Matrix/chemistry , Decellularized Extracellular Matrix/pharmacology , Electrochemical Techniques , Rats , Tissue Engineering
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