Toward guided tissue and bone regeneration: morphology, attachment, proliferation, and migration of cells cultured on collagen barrier membranes. a systematic review

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Odontology (2008) 96:1–11 DOI 10.1007/s10266-008-0087-y

© The Society of The Nippon Dental University 2008

REVIEW ARTICLE Jan Behring · Rüdiger Junker · X. Frank Walboomers Betsy Chessnut · John A. Jansen

Toward guided tissue and bone regeneration: morphology, attachment, proliferation, and migration of cells cultured on collagen barrier membranes. A systematic review

Received:January 20, 2008 / Accepted: April 23, 2008

Abstract Collagen barrier membranes are frequently used in both guided tissue regeneration (GTR) and guided bone regeneration (GBR). Collagen used for these devices is available from different species and is often processed to alter the properties of the final product. This is necessary because unprocessed collagen is rapidly resorbed in vivo and demands forbarrier membranes are different in GTR and GBR. This systematic literature review attempts to evaluate possible effects of collagen origin and mode of cross-linking on the potential of different cells to attach to, proliferate on, and migrate over barrier membranes in vitro. Seventeen original studies, selected by a systematic process, are included in this review. The results show that fibroblastsof different species and originating tissues as well as boneforming cells are able to attach to collagen membranes irrespective of collagen origin or mode of processing. Different cell types behave differently on identical membranes. Many pieces of evidence are currently available, and we attempted to elucidate the effects of collagen origin and mode of processing on cellular behavior, butfurther research will be required before it will be possible to predict for certain the effect a specific procedure will have with a given product. Key words Guided tissue regeneration · Guided bone regeneration · Collagen · In vitro · Membrane

In guided tissue regeneration (GTR) and guided bone regeneration (GBR), barrier membranes are used to separate the area of the defect into twocompartments.
J. Behring (*) · R. Junker · X.F. Walboomers · B. Chessnut · J.A. Jansen Department of Periodontology and Biomaterials, Radboud University Nijmegen Medical Centre, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands Tel. +31 24 3614006; Fax +31 24 3541314 e-mail:

An ideal resorbable membrane for these techniques should facilitate the attachment, proliferation,and migration of cells on its surface in order to seal the underlying defect off from the oral flora, even in the case of membrane exposure. The adherence of connective tissue cells to the inside of a membrane promotes periodontal regeneration,1 and an attachment can help to stabilize the blood clot and integrate the membrane into the tissue.2 Collagen is the main structural macromolecule of thehuman body and can easily be reconstituted into the different shapes needed in medicine, including occlusive membranes. However, native collagen is degraded within a few days, and untreated collagen membranes lack stability to maintain space if bony support is missing.3 To overcome these problems, various cross-linking techniques have been developed. Cross-linking involves the multiplication ofnaturally occurring links between collagen molecules.4 This leads to stiffer collagen membranes and slows down enzymatic degradation.5 Both properties seem to be dose- or time-dependent, depending on the mode of cross-linking. This means that the number of collagen crosslinks is proportional to both the stiffness of the membrane and the degradation time.6,7 The most frequently used crosslinking methodis to tan the collagen with glutaraldehyde (GA), which, although an effective cross-linking agent, has been shown in vitro8 and in vivo9 to increase the cytotoxicity of collagen membranes. GA is released during collagen degradation, and a constant release of remnant (nonreacted) GA has been shown to inhibit cell proliferation. Therefore, several other techniques to cross-link collagen have been...
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