Document Detail

Effects of crosslinking degree of an acellular biological tissue on its tissue regeneration pattern.
MedLine Citation:
PMID:  15020128     Owner:  NLM     Status:  MEDLINE    
It was reported that acellular biological tissues can provide a natural microenvironment for host cell migration and may be used as a scaffold for tissue regeneration. To reduce antigenicity, biological tissues have to be fixed with a crosslinking agent before implantation. As a tissue-engineering scaffold, it is speculated that the crosslinking degree of an acellular tissue may affect its tissue regeneration pattern. In the study, a cell extraction process was employed to remove the cellular components from bovine pericardia. The acellular tissues then were fixed with genipin at various known concentrations to obtain varying degrees of crosslinking. It was shown in the in vitro degradation study that after fixing with genipin, the resistance against enzymatic degradation of the acellular tissue increased significantly with increasing its crosslinking degree. In the in vivo subcutaneous study, it was found that cells (inflammatory cells, fibroblasts, endothelial cells, and red blood cells) were able to infiltrate into acellular tissues. Generally, the depth of cell infiltration into the acellular tissue decreased with increasing its crosslinking degree. Infiltration of inflammatory cells was accompanied by degradation of the acellular tissue. Due to early degradation, no tissue regeneration was observed within fresh (without crosslinking) and the 30%-degree-crosslinking acellular tissues. This is because the scaffolds provided by these two samples were already completely degraded before the infiltrated cells began to secrete their own extracellular matrix. In contrast, tissue regeneration (fibroblasts, neo-collagen fibrils, and neo-capillaries) was observed for the 60%- and 95%-degree-crosslinking acellular tissues by the histological examination, immunohistological staining, transmission electron microscopy, and denaturation temperature measurement. The 95%-degree-crosslinking acellular tissue was more resistant against enzymatic degradation than its 60%-degree-crosslinking counterpart. Consequently, tissue regeneration was limited in the outer layer of the 95%-degree-crosslinking acellular tissue throughout the entire course of the study (1-year postoperatively), while tissue regeneration was observed within the entire sample for the 60%-degree-crosslinking acellular tissue. In conclusion, the crosslinking degree determines the degradation rate of the acellular tissue and its tissue regeneration pattern.
Huang-Chien Liang; Yen Chang; Cheng-Kuo Hsu; Meng-Horng Lee; Hsing-Wen Sung
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Publication Detail:
Type:  Comparative Study; Evaluation Studies; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Biomaterials     Volume:  25     ISSN:  0142-9612     ISO Abbreviation:  Biomaterials     Publication Date:  2004 Aug 
Date Detail:
Created Date:  2004-03-15     Completed Date:  2004-10-27     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  8100316     Medline TA:  Biomaterials     Country:  England    
Other Details:
Languages:  eng     Pagination:  3541-52     Citation Subset:  IM    
Department of Chemical Engineering, National Tsing Hua University, Hsinchu 30013, Taiwan, ROC.
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MeSH Terms
Biocompatible Materials / chemistry
Cell Extracts / chemistry*
Cell-Free System / chemistry
Connective Tissue / pathology
Cross-Linking Reagents / chemistry
Extracellular Matrix / chemistry*,  physiology*
Foreign-Body Reaction / pathology
Materials Testing
Pericardium / chemistry*
Prostheses and Implants
Pyrans / chemistry*
Rats, Wistar
Regeneration / physiology*
Surface Properties
Tensile Strength
Tissue Engineering / methods*
Reg. No./Substance:
0/Biocompatible Materials; 0/Cell Extracts; 0/Cross-Linking Reagents; 0/Iridoids; 0/Pyrans; 6902-77-8/genipin

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