Contributing to organ formation and tissue regeneration, extracellular matrix (ECM) constituents provide tissue with three-dimensional (3D) structural integrity and cellular-function regulation. Containing the crucial traits of the cellular microenvironment, ECM substitutes mediate cell-matrix interactions to prompt stem-cell proliferation and differentiation for 3D organoid construction in vitro or tissue regeneration in vivo. However, these ECMs are often applied generically and have yet to be extensively developed for specific cell types in 3D cultures. Cultured cells also produce rich ECM, particularly stromal cells. Cellular ECM improves 3D culture development in vitro and tissue remodeling during wound healing after implantation into the host as well. Gaining better insight into ECM derived from either tissue or cells that regulate 3D tissue reconstruction or organ regeneration helps us to select, produce, and implant the most suitable ECM and thus promote 3D organoid culture and tissue remodeling for in vivo regeneration. Overall, the decellularization methodologies and tissue/cell-derived ECM as scaffolds or cellular-growth supplements used in cell propagation and differentiation for 3D tissue culture in vitro are discussed. Moreover, current preclinical applications by which ECM components modulate the wound-healing process are reviewed.
Cell Differentiation ; Cell Proliferation ; Decellularized Extracellular Matrix ; Extracellular Matrix/metabolism* ; Humans ; Mesenchymal Stem Cells ; Tissue Engineering/methods* ; Tissue Scaffolds/chemistry*

Pericellular matrix (PCM) is a narrow tissue region surrounding chondrocytes, which "chondron" with its enclosed cells. A number of studies suggested that PCM is rich in proteoglycans, collagen and fibronectin, and plays an important role in regulating microenvironment of chondrocytes. Direct measures of PCM properties through micropipette aspiration technique showed that PCM was different from mechanical property of chondrocytes and nature extracellular matrix. However, the function of PCM is not clear, and need further study.
Animals ; Biomechanical Phenomena ; Chondrocytes ; chemistry ; cytology ; metabolism ; Extracellular Matrix ; chemistry ; metabolism ; Humans

Cartilage oligomeric matrix protein (COMP) is a potential biomarker for joint destruction associated with osteoarthritis, which is first and best investigated biomarkers to reflect osteoarthritis occurs, progress and the prognosis. In this article, multiple uses and related reports of COMP are summarized briefly to promote further investigation of COMP.
Biomarkers ; blood ; Cartilage Oligomeric Matrix Protein ; Extracellular Matrix Proteins ; blood ; chemistry ; metabolism ; Glycoproteins ; blood ; chemistry ; metabolism ; Humans ; Matrilin Proteins ; Osteoarthritis ; blood ; diagnosis ; Prognosis

Collagen, which widely exists in skin, bone, muscle and other tissues, is a major structural protein in mammalian extracellular matrix. It participates in cell proliferation, differentiation, migration and signal transmission, plays an important role in tissue support and repair and exerts a protective effect. Collagen is widely used in tissue engineering, clinical medicine, food industry, packaging materials, cosmetics and medical beauty due to its good biological characteristics. This paper reviews the biological characteristics of collagen and its application in bioengineering research and development in recent years. Finally, we prospect the future application of collagen as a biomimetic material.
Animals ; Collagen/analysis* ; Tissue Engineering/methods* ; Extracellular Matrix/metabolism* ; Biomimetic Materials/chemistry* ; Bone and Bones ; Tissue Scaffolds ; Mammals/metabolism*

Articular cartilage is a connective tissue consisting of a specialized extracellular matrix (ECM) that dominates the bulk of its wet and dry weight. Type II collagen and aggrecan are the main ECM proteins in cartilage. However, little attention has been paid to less abundant molecular components, especially minor collagens, including type IV, VI, IX, X, XI, XII, XIII, and XIV, etc. Although accounting for only a small fraction of the mature matrix, these minor collagens not only play essential structural roles in the mechanical properties, organization, and shape of articular cartilage, but also fulfil specific biological functions. Genetic studies of these minor collagens have revealed that they are associated with multiple connective tissue diseases, especially degenerative joint disease. The progressive destruction of cartilage involves the degradation of matrix constituents including these minor collagens. The generation and release of fragmented molecules could generate novel biochemical markers with the capacity to monitor disease progression, facilitate drug development and add to the existing toolbox for in vitro studies, preclinical research and clinical trials.
Aggrecans ; chemistry ; genetics ; metabolism ; Animals ; Biomarkers ; metabolism ; Cartilage, Articular ; chemistry ; metabolism ; pathology ; Collagen ; chemistry ; classification ; genetics ; metabolism ; Extracellular Matrix Proteins ; chemistry ; genetics ; metabolism ; Gene Expression ; Humans ; Osteoarthritis ; diagnosis ; genetics ; metabolism ; pathology ; Protein Isoforms ; chemistry ; classification ; genetics ; metabolism

The topography structure of biomaterial is one of the most important factors which affect cells' behaviors, including cell adhesion, proliferation, differentiation and apoptosis. With the development of nanobiology and technology, it is well known that cells could sense and respond to the nanotopography of material's substratum with "contact guidance", and the nanotopography of the substratum has potential application and significance to tissue regeneration and rehabilitation. In this article, various methods to constitute nanotopography including polymer demixing, electrospinning, electron beam lithography as well as chemical grafting were reviewed, the effects of nanotopography on cells' growth behavior and reconstruction of extracellular matrix were analyzed, and the important functions of nanotopography construction to the cell-material interaction at the molecular and cellular level were discussed.
Biocompatible Materials ; chemistry ; Cell Adhesion ; Cell Culture Techniques ; Cells, Cultured ; Extracellular Matrix ; metabolism ; Humans ; Nanotechnology ; Surface Properties ; Tissue Engineering ; methods

OBJECTIVESTo study cartilage oligomeric matrix protein (COMP) mRNA and protein expression in normal pancreas, chronic pancreatitis (CP), and pancreatic cancer tissues.

METHODSTissues from 15 cases of normal pancreas, 14 cases of chronic pancreatitis and 14 cases of pancreatic cancer were analyzed by Northern blot, Western blot, in situ hybridization and immunohistochemistry.

RESULTSCOMP mRNA signals and immunoreactivity were strongly present in the cytoplasm of degenerating acinar cells in CP tissues as well as in CP-like lesions in pancreatic cancer tissues. In contrast, COMP expression was weak to absent in the cytoplasm of cancer cells in pancreatic cancer tissues, and in ductal cells and islet cells in normal pancreatic tissues.

CONCLUSIONCOMP is preferentially expressed in degenerating acinar cells in CP and in CP-like areas in pancreatic cancer, suggesting a potential role of this molecular in acinar cell dysfunction in CP.

Blotting, Northern ; Blotting, Western ; Cartilage Oligomeric Matrix Protein ; Dimerization ; Extracellular Matrix Proteins ; chemistry ; genetics ; metabolism ; Glycoproteins ; chemistry ; genetics ; metabolism ; Humans ; Immunohistochemistry ; In Situ Hybridization ; Matrilin Proteins ; Pancreas ; metabolism ; pathology ; Pancreatic Neoplasms ; metabolism ; pathology ; Pancreatitis, Chronic ; metabolism ; pathology ; RNA, Messenger ; genetics ; metabolism

Hepatic fibrogenesis, a complex process that involves a marked accumulation of extracellular matrix components, activation of cells capable of producing matrix materials, cytokine release, and tissue remodeling, is regulated by matrix metalloproteinases (MMPs) and tissue inhibitors of metalloproteinases (TIMPs). The MMP-TIMP balance can regulate liver fibrogenesis. The aim of this study was to evaluate the expression patterns of MMPs and TIMPs during thioacetamide (TAA)-induced liver fibrogenesis. Chronic liver injury was induced with TAA (200 mg/kg i.p.) for 4 or 7 weeks in male Sprague-Dawley rats. Hepatic injury and fibrosis were assessed by hematoxylin-eosin (H&E) staining, and collagen deposition was confirmed by Sirius Red staining. The level of hepatic injury was quantified by serological analysis. The transcriptional and translational levels of alpha-smooth muscle actin (alpha-SMA), MMPs, and TIMPs in the liver were measured by Western blotting, RT-PCR, and immunohistochemistry. MMP, TIMP, and alpha-SMA were observed along fibrotic septa and portal spaces around the lobules. TAA treatment increased transcription of both MMPs and TIMPs, but only TIMPs showed increased translation. The dominant expression of TIMPs may regulate the function of MMPs to maintain liver fibrosis induced by TAA.
Animals ; Collagen/metabolism ; Extracellular Matrix/chemistry/metabolism ; *Liver Cirrhosis/chemically induced/metabolism/pathology ; Male ; Matrix Metalloproteinases/genetics/*metabolism ; Rats ; Rats, Sprague-Dawley ; Thioacetamide/*toxicity ; Tissue Inhibitor of Metalloproteinases/genetics/*metabolism

This study was intended to investigate the crosslinking characteristics of a new crosslinking agent-oxidized sodium alginate (ADA), which might provide an ideal biological crosslinking reagent for the construction of soft tissue bioprostheses. Glutaraldehyde and genipin, which have been typically used in developing bioprostheses, were used as controls. The porcine aortas were treated by these three crosslinking agents for 15 min to 72 h and the fixation index was determined. Subsequently, the mechanical property and cytocompatibility of fixed tissues were also tested. The results indicated that fixed tissues by ADA were comparable as glutaraldehyde and superior to genipin controls in fixative efficiency. It was also found that tissues fixed by ADA were comparable as genipin and superior to glutaraldehyde controls in cytocompatibility and were similar to natural tissues in mechanical property. The results of in vitro study demonstrated that ADA could be a promising crosslinking reagent for biological tissue fixation.
Alginates ; chemistry ; pharmacology ; Animals ; Aorta ; cytology ; metabolism ; Biocompatible Materials ; metabolism ; Cross-Linking Reagents ; chemistry ; pharmacology ; Extracellular Matrix ; metabolism ; Glucuronic Acid ; chemistry ; pharmacology ; Hexuronic Acids ; chemistry ; pharmacology ; Swine ; Tissue Engineering ; methods ; Tissue Fixation ; Tissue Scaffolds

This study was purposed to establish a new inducing system for differentiation of human embryonic stem cells into hematopoietic progenitor cells and to explore the effect of different extracellular matrices (DEM) on production of hematopoietic cells. The 3 kinds of extracellular matrices-matrigel, fibronectin and IV type collagen (collagen IV) were chosen to package cultured plates, the direct adherent culture on extracellular matrix was used, and the hematopoietic growth factors were added into cultured plates to induce the differentiation of human embryonic stem cells into hematopoietic progenitor cells. The hematopoietic colony forming unit assay was used to determine the yielded colony forming cells, the flow cytometry and real-time quantitative PCR were used to detect the expression of markers specific to hematopoiesis and the effect of 3 extracellular matrices on production of hematopoietic progenitor cells was compared. The results showed that after being induced for 14 days, the total yield of colony forming cells, the ratio of CD34(+) cells and the expression level of SCL and CD34 on collagen IV were significantly higher than those on matrigel and fibronectin groups (P < 0.05). It is concluded that human embryonic stem cells can efficiently differentiate into hematopoietic progenitor cells by direct adherent culture on extracellular matrices, and the collagen IV can improve the hematopoietic differentiation of human embryonic stem cells.
Antigens, CD34 ; metabolism ; Cell Differentiation ; Collagen ; chemistry ; Collagen Type IV ; chemistry ; Drug Combinations ; Embryonic Stem Cells ; cytology ; Extracellular Matrix ; chemistry ; Fibronectins ; chemistry ; Flow Cytometry ; Hematopoietic Stem Cells ; cytology ; Humans ; Laminin ; chemistry ; Proteoglycans ; chemistry