Skip to main content
Top
Published in: Head & Face Medicine 1/2014

Open Access 01-12-2014 | Research

Biodegradation pattern and tissue integration of native and cross-linked porcine collagen soft tissue augmentation matrices – an experimental study in the rat

Authors: Daniel Rothamel, Marcel Benner, Tim Fienitz, Arndt Happe, Matthias Kreppel, Hans-Joachim Nickenig, Joachim E Zöller

Published in: Head & Face Medicine | Issue 1/2014

Login to get access

Abstract

Introduction

Within the last decades, collagen types I and III have been established as a sufficient biomaterial for GBR and GTR procedures. They might also be an adequate matrix for soft tissue augmentations. However, collagen materials differ significantly regarding resorption time, biodegradation pattern and the invasion of inflammatory cells.
The aim of the present study was to compare the biodegradation and tissue integration of native, differently processed and cross-linked collagen scaffolds in rats.

Methods

Four experimental porcine collagen matrices of 1.0 mm thickness, developed for soft tissue augmentation procedures, were tested. Based on the same native dermal Type I and III collagen, native (ND, Mucoderm® prototype), specifically defatted (DD), ethylene dioxide cross-linked (ECL) and dehydrothermally cross-linked (DCL) dermis collagen (AAP/Botiss Biomaterials, Berlin, Germany) were evaluated. Two specimens of 1 × 1 cm were fixed around a non-absorbable spacer using non-absorbable sutures. After rehydration, specimens (N = 8) were randomly allocated in unconnected subcutaneous pouches on the back of 40 Wistar rats. Rats were divided into five groups (1, 2, 4, 8 and 12 weeks), including eight animals each. After each period, eight rats were sacrificed and explanted specimens were prepared for histological analysis. The following parameters were evaluated: membrane thickness as a sign of biodegradation and volume stability, cell ingrowth, vascularization, tissue integration and foreign body reaction.

Results

Biodegradation pattern of the non cross-linked collagen scaffolds differed only slightly in terms of presence of inflammatory cells and cell invasion into the matrix. In terms of biodegradation, ECL displayed a considerable slower resorption than ND, DCL and DD. Chemical cross-linking using ethylene dioxide showed a significant higher invasion of inflammatory cells.

Conclusion

Within the limits of the present study it was concluded that the processing techniques influenced the collagen properties in a different intensity. Dehydrothermal cross-linking and special defatting did not notably change the biodegradation pattern, whereas cross-linking using ethylene dioxide led to significant higher volume stability of the matrix. However, ECL showed an increased inflammatory response and compromised tissue integration. Therefore, ethylene dioxide seems to be not suitable for stabilization of collagen matrices for soft tissue augmentation procedures.
Appendix
Available only for authorised users
Literature
1.
go back to reference Gottlow J, Nyman S, Lindhe J, Karring T, Wennstrom J: New attachment formation in the human periodontium by guided tissue regeneration. Case reports. J Clin Periodontol. 1986, 13: 604-616. 10.1111/j.1600-051X.1986.tb00854.x.CrossRefPubMed Gottlow J, Nyman S, Lindhe J, Karring T, Wennstrom J: New attachment formation in the human periodontium by guided tissue regeneration. Case reports. J Clin Periodontol. 1986, 13: 604-616. 10.1111/j.1600-051X.1986.tb00854.x.CrossRefPubMed
2.
go back to reference Dahlin C, Linde A, Gottlow J, Nyman S: Healing of bone defects by guided tissue regeneration. Plast Reconstr Surg. 1988, 81: 672-676. 10.1097/00006534-198805000-00004.CrossRefPubMed Dahlin C, Linde A, Gottlow J, Nyman S: Healing of bone defects by guided tissue regeneration. Plast Reconstr Surg. 1988, 81: 672-676. 10.1097/00006534-198805000-00004.CrossRefPubMed
3.
go back to reference Karring T, Nyman S, Gottlow J, Laurell L: Development of the biological concept of guided tissue regeneration–animal and human studies. Periodontol 2000. 1993, 1: 26-35. 10.1111/j.1600-0757.1993.tb00204.x.CrossRef Karring T, Nyman S, Gottlow J, Laurell L: Development of the biological concept of guided tissue regeneration–animal and human studies. Periodontol 2000. 1993, 1: 26-35. 10.1111/j.1600-0757.1993.tb00204.x.CrossRef
4.
go back to reference Hammerle CH, Karring T: Guided bone regeneration at oral implant sites. Periodontol 2000. 1998, 17: 151-175. 10.1111/j.1600-0757.1998.tb00132.x.CrossRefPubMed Hammerle CH, Karring T: Guided bone regeneration at oral implant sites. Periodontol 2000. 1998, 17: 151-175. 10.1111/j.1600-0757.1998.tb00132.x.CrossRefPubMed
5.
go back to reference Hammerle CH, Lang NP: Single stage surgery combining transmucosal implant placement with guided bone regeneration and bioresorbable materials. Clin Oral Implants Res. 2001, 12: 9-18. 10.1034/j.1600-0501.2001.012001009.x.CrossRefPubMed Hammerle CH, Lang NP: Single stage surgery combining transmucosal implant placement with guided bone regeneration and bioresorbable materials. Clin Oral Implants Res. 2001, 12: 9-18. 10.1034/j.1600-0501.2001.012001009.x.CrossRefPubMed
6.
go back to reference Schlegel AK, Mohler H, Busch F, Mehl A: Preclinical and clinical studies of a collagen membrane (Bio-Gide). Biomaterials. 1997, 18: 535-538. 10.1016/S0142-9612(96)00175-5.CrossRefPubMed Schlegel AK, Mohler H, Busch F, Mehl A: Preclinical and clinical studies of a collagen membrane (Bio-Gide). Biomaterials. 1997, 18: 535-538. 10.1016/S0142-9612(96)00175-5.CrossRefPubMed
7.
go back to reference Postlethwaite AE, Seyer JM, Kang AH: Chemotactic attraction of human fibroblasts to type I, II, and III collagens and collagen-derived peptides. Proc Natl Acad Sci U S A. 1978, 75: 871-875. 10.1073/pnas.75.2.871.CrossRefPubMedPubMedCentral Postlethwaite AE, Seyer JM, Kang AH: Chemotactic attraction of human fibroblasts to type I, II, and III collagens and collagen-derived peptides. Proc Natl Acad Sci U S A. 1978, 75: 871-875. 10.1073/pnas.75.2.871.CrossRefPubMedPubMedCentral
8.
go back to reference Yaffe A, Ehrlich J, Shoshan S: Restoration of periodontal attachment employing enriched collagen solution in the dog. J Periodontol. 1984, 55: 623-628. 10.1902/jop.1984.55.11.623.CrossRefPubMed Yaffe A, Ehrlich J, Shoshan S: Restoration of periodontal attachment employing enriched collagen solution in the dog. J Periodontol. 1984, 55: 623-628. 10.1902/jop.1984.55.11.623.CrossRefPubMed
9.
go back to reference Hutmacher D, Hurzeler MB, Schliephake H: A review of material properties of biodegradable and bioresorbable polymers and devices for GTR and GBR applications. Int J Oral Maxillofac Implants. 1996, 11: 667-678.PubMed Hutmacher D, Hurzeler MB, Schliephake H: A review of material properties of biodegradable and bioresorbable polymers and devices for GTR and GBR applications. Int J Oral Maxillofac Implants. 1996, 11: 667-678.PubMed
10.
go back to reference Locci P, Calvitti M, Belcastro S, Pugliese M, Guerra M, Marinucci L, Staffolani N, Becchetti E: Phenotype expression of gingival fibroblasts cultured on membranes used in guided tissue regeneration. J Periodontol. 1997, 68: 857-863. 10.1902/jop.1997.68.9.857.CrossRefPubMed Locci P, Calvitti M, Belcastro S, Pugliese M, Guerra M, Marinucci L, Staffolani N, Becchetti E: Phenotype expression of gingival fibroblasts cultured on membranes used in guided tissue regeneration. J Periodontol. 1997, 68: 857-863. 10.1902/jop.1997.68.9.857.CrossRefPubMed
11.
go back to reference Hardwick R, Hayes BK, Flynn C: Devices for dentoalveolar regeneration: an up-to-date literature review. J Periodontol. 1995, 66: 495-505. 10.1902/jop.1995.66.6.495.CrossRefPubMed Hardwick R, Hayes BK, Flynn C: Devices for dentoalveolar regeneration: an up-to-date literature review. J Periodontol. 1995, 66: 495-505. 10.1902/jop.1995.66.6.495.CrossRefPubMed
12.
go back to reference Rothamel D, Schwarz F, Fienitz T, Smeets R, Dreiseidler T, Ritter L, Happe A, Zoller J: Biocompatibility and biodegradation of a native porcine pericardium membrane: results of in vitro and in vivo examinations. Int J Oral Maxillofac Implants. 2012, 27: 146-154.PubMed Rothamel D, Schwarz F, Fienitz T, Smeets R, Dreiseidler T, Ritter L, Happe A, Zoller J: Biocompatibility and biodegradation of a native porcine pericardium membrane: results of in vitro and in vivo examinations. Int J Oral Maxillofac Implants. 2012, 27: 146-154.PubMed
13.
go back to reference Rothamel D, Schwarz F, Stoldt V, Herten M, Kotthaus C, Becker J: In vitro testing of thrombocyte adhesion to different collagenous hemostyptic agents. Mund Kiefer Gesichtschir. 2006, 10: 148-154. 10.1007/s10006-006-0681-5.CrossRefPubMed Rothamel D, Schwarz F, Stoldt V, Herten M, Kotthaus C, Becker J: In vitro testing of thrombocyte adhesion to different collagenous hemostyptic agents. Mund Kiefer Gesichtschir. 2006, 10: 148-154. 10.1007/s10006-006-0681-5.CrossRefPubMed
14.
go back to reference Schwarz F, Rothamel D, Herten M, Wustefeld M, Sager M, Ferrari D, Becker J: Immunohistochemical characterization of guided bone regeneration at a dehiscence-type defect using different barrier membranes: an experimental study in dogs. Clin Oral Implants Res. 2008, 19: 402-415. 10.1111/j.1600-0501.2007.01486.x.CrossRefPubMed Schwarz F, Rothamel D, Herten M, Wustefeld M, Sager M, Ferrari D, Becker J: Immunohistochemical characterization of guided bone regeneration at a dehiscence-type defect using different barrier membranes: an experimental study in dogs. Clin Oral Implants Res. 2008, 19: 402-415. 10.1111/j.1600-0501.2007.01486.x.CrossRefPubMed
15.
go back to reference Caffesse RG, de la Rosa M, Mota LF: Regeneration of soft and hard tissue periodontal defects. Am J Dent. 2002, 15: 339-345.PubMed Caffesse RG, de la Rosa M, Mota LF: Regeneration of soft and hard tissue periodontal defects. Am J Dent. 2002, 15: 339-345.PubMed
16.
go back to reference Cranin AN: Implant surgery: the management of soft tissues. J Oral Implantol. 2002, 28: 230-237. 10.1563/1548-1336(2002)028<0230:ISTMOS>2.3.CO;2.CrossRefPubMed Cranin AN: Implant surgery: the management of soft tissues. J Oral Implantol. 2002, 28: 230-237. 10.1563/1548-1336(2002)028<0230:ISTMOS>2.3.CO;2.CrossRefPubMed
17.
go back to reference Klinge B, Flemmig TF, Working G: Tissue augmentation and esthetics (Working Group 3). Clin Oral Implants Res. 2009, 20 (Suppl 4): 166-170.CrossRefPubMed Klinge B, Flemmig TF, Working G: Tissue augmentation and esthetics (Working Group 3). Clin Oral Implants Res. 2009, 20 (Suppl 4): 166-170.CrossRefPubMed
18.
go back to reference Thoma DS, Benic GI, Zwahlen M, Hammerle CH, Jung RE: A systematic review assessing soft tissue augmentation techniques. Clin Oral Implants Res. 2009, 20 (Suppl 4): 146-165.CrossRefPubMed Thoma DS, Benic GI, Zwahlen M, Hammerle CH, Jung RE: A systematic review assessing soft tissue augmentation techniques. Clin Oral Implants Res. 2009, 20 (Suppl 4): 146-165.CrossRefPubMed
19.
go back to reference Sullivan HC, Atkins JH: The role of free gingival grafts in periodontal therapy. Dent Clin N Am. 1969, 13: 133-148.PubMed Sullivan HC, Atkins JH: The role of free gingival grafts in periodontal therapy. Dent Clin N Am. 1969, 13: 133-148.PubMed
20.
go back to reference Edel A: Clinical evaluation of free connective tissue grafts used to increase the width of keratinised gingiva. J Clin Periodontol. 1974, 1: 185-196. 10.1111/j.1600-051X.1974.tb01257.x.CrossRefPubMed Edel A: Clinical evaluation of free connective tissue grafts used to increase the width of keratinised gingiva. J Clin Periodontol. 1974, 1: 185-196. 10.1111/j.1600-051X.1974.tb01257.x.CrossRefPubMed
21.
go back to reference Wessel JR, Tatakis DN: Patient outcomes following subepithelial connective tissue graft and free gingival graft procedures. J Periodontol. 2008, 79: 425-430. 10.1902/jop.2008.070325.CrossRefPubMed Wessel JR, Tatakis DN: Patient outcomes following subepithelial connective tissue graft and free gingival graft procedures. J Periodontol. 2008, 79: 425-430. 10.1902/jop.2008.070325.CrossRefPubMed
22.
go back to reference Studer SP, Allen EP, Rees TC, Kouba A: The thickness of masticatory mucosa in the human hard palate and tuberosity as potential donor sites for ridge augmentation procedures. J Periodontol. 1997, 68: 145-151. 10.1902/jop.1997.68.2.145.CrossRefPubMed Studer SP, Allen EP, Rees TC, Kouba A: The thickness of masticatory mucosa in the human hard palate and tuberosity as potential donor sites for ridge augmentation procedures. J Periodontol. 1997, 68: 145-151. 10.1902/jop.1997.68.2.145.CrossRefPubMed
23.
go back to reference Sanz M, Lorenzo R, Aranda JJ, Martin C, Orsini M: Clinical evaluation of a new collagen matrix (Mucograft prototype) to enhance the width of keratinized tissue in patients with fixed prosthetic restorations: a randomized prospective clinical trial. J Clin Periodontol. 2009, 36: 868-876. 10.1111/j.1600-051X.2009.01460.x.CrossRefPubMed Sanz M, Lorenzo R, Aranda JJ, Martin C, Orsini M: Clinical evaluation of a new collagen matrix (Mucograft prototype) to enhance the width of keratinized tissue in patients with fixed prosthetic restorations: a randomized prospective clinical trial. J Clin Periodontol. 2009, 36: 868-876. 10.1111/j.1600-051X.2009.01460.x.CrossRefPubMed
24.
go back to reference Tatakis DN, Promsudthi A, Wikesjo UM: Devices for periodontal regeneration. Periodontol 2000. 1999, 19: 59-73. 10.1111/j.1600-0757.1999.tb00147.x.CrossRefPubMed Tatakis DN, Promsudthi A, Wikesjo UM: Devices for periodontal regeneration. Periodontol 2000. 1999, 19: 59-73. 10.1111/j.1600-0757.1999.tb00147.x.CrossRefPubMed
25.
go back to reference Rothamel D, Schwarz F, Sager M, Herten M, Sculean A, Becker J: Biodegradation of differently cross-linked collagen membranes: an experimental study in the rat. Clin Oral Implants Res. 2005, 16: 369-378. 10.1111/j.1600-0501.2005.01108.x.CrossRefPubMed Rothamel D, Schwarz F, Sager M, Herten M, Sculean A, Becker J: Biodegradation of differently cross-linked collagen membranes: an experimental study in the rat. Clin Oral Implants Res. 2005, 16: 369-378. 10.1111/j.1600-0501.2005.01108.x.CrossRefPubMed
26.
go back to reference Owens KW, Yukna RA: Collagen membrane resorption in dogs: a comparative study. Implant Dent. 2001, 10: 49-58. 10.1097/00008505-200101000-00016.CrossRefPubMed Owens KW, Yukna RA: Collagen membrane resorption in dogs: a comparative study. Implant Dent. 2001, 10: 49-58. 10.1097/00008505-200101000-00016.CrossRefPubMed
27.
go back to reference Moses O, Vitrial D, Aboodi G, Sculean A, Tal H, Kozlovsky A, Artzi Z, Weinreb M, Nemcovsky CE: Biodegradation of three different collagen membranes in the rat calvarium: a comparative study. J Periodontol. 2008, 79: 905-911. 10.1902/jop.2008.070361.CrossRefPubMed Moses O, Vitrial D, Aboodi G, Sculean A, Tal H, Kozlovsky A, Artzi Z, Weinreb M, Nemcovsky CE: Biodegradation of three different collagen membranes in the rat calvarium: a comparative study. J Periodontol. 2008, 79: 905-911. 10.1902/jop.2008.070361.CrossRefPubMed
28.
go back to reference Annen BM, Ramel CF, Hammerle CH, Jung RE: Use of a new cross-linked collagen membrane for the treatment of peri-implant dehiscence defects: a randomised controlled double-blinded clinical trial. Eur J Oral Implantol. 2011, 4: 87-100.PubMed Annen BM, Ramel CF, Hammerle CH, Jung RE: Use of a new cross-linked collagen membrane for the treatment of peri-implant dehiscence defects: a randomised controlled double-blinded clinical trial. Eur J Oral Implantol. 2011, 4: 87-100.PubMed
29.
go back to reference Hurley LA, Stinchfield FE, Bassett AL, Lyon WH: The role of soft tissues in osteogenesis. An experimental study of canine spine fusions. J Bone Joint Surg. 1959, 41-A: 1243-1254.PubMed Hurley LA, Stinchfield FE, Bassett AL, Lyon WH: The role of soft tissues in osteogenesis. An experimental study of canine spine fusions. J Bone Joint Surg. 1959, 41-A: 1243-1254.PubMed
30.
go back to reference Sionkowska A, Kozlowska J: Properties and modification of porous 3-D collagen/hydroxyapatite composites. Int J Biol Macromol. 2012, 52C: 250-259. Sionkowska A, Kozlowska J: Properties and modification of porous 3-D collagen/hydroxyapatite composites. Int J Biol Macromol. 2012, 52C: 250-259.
31.
go back to reference Khouw IM, van Wachem PB, Molema G, Plantinga JA, de Leij LF, van Luyn MJ: The foreign body reaction to a biodegradable biomaterial differs between rats and mice. J Biomed Mater Res. 2000, 52: 439-446. 10.1002/1097-4636(20001205)52:3<439::AID-JBM1>3.0.CO;2-C.CrossRefPubMed Khouw IM, van Wachem PB, Molema G, Plantinga JA, de Leij LF, van Luyn MJ: The foreign body reaction to a biodegradable biomaterial differs between rats and mice. J Biomed Mater Res. 2000, 52: 439-446. 10.1002/1097-4636(20001205)52:3<439::AID-JBM1>3.0.CO;2-C.CrossRefPubMed
32.
go back to reference Paul BF, Mellonig JT, Towle HJ, Gray JL: Use of a collagen barrier to enhance healing in human periodontal furcation defects. Int J Periodontics Restorative Dent. 1992, 12: 123-131.PubMed Paul BF, Mellonig JT, Towle HJ, Gray JL: Use of a collagen barrier to enhance healing in human periodontal furcation defects. Int J Periodontics Restorative Dent. 1992, 12: 123-131.PubMed
33.
go back to reference Sela MN, Kohavi D, Krausz E, Steinberg D, Rosen G: Enzymatic degradation of collagen-guided tissue regeneration membranes by periodontal bacteria. Clin Oral Implants Res. 2003, 14: 263-268. 10.1034/j.1600-0501.2003.140302.x.CrossRefPubMed Sela MN, Kohavi D, Krausz E, Steinberg D, Rosen G: Enzymatic degradation of collagen-guided tissue regeneration membranes by periodontal bacteria. Clin Oral Implants Res. 2003, 14: 263-268. 10.1034/j.1600-0501.2003.140302.x.CrossRefPubMed
34.
go back to reference Shanmugam M, Sivakumar V, Anitha V, Sivakumar B: Clinical evaluation of alloderm for root coverage and colour match. J Indian Soc Periodontol. 2012, 16: 218-223. 10.4103/0972-124X.99265.CrossRefPubMedPubMedCentral Shanmugam M, Sivakumar V, Anitha V, Sivakumar B: Clinical evaluation of alloderm for root coverage and colour match. J Indian Soc Periodontol. 2012, 16: 218-223. 10.4103/0972-124X.99265.CrossRefPubMedPubMedCentral
35.
go back to reference Gholami GA, Saberi A, Kadkhodazadeh M, Amid R, Karami D: Comparison of the clinical outcomes of connective tissue and acellular dermal matrix in combination with double papillary flap for root coverage: A 6-month trial. Dent Res J. 2013, 10: 506-513. Gholami GA, Saberi A, Kadkhodazadeh M, Amid R, Karami D: Comparison of the clinical outcomes of connective tissue and acellular dermal matrix in combination with double papillary flap for root coverage: A 6-month trial. Dent Res J. 2013, 10: 506-513.
36.
go back to reference Park JB: Increasing the width of keratinized mucosa around endosseous implant using acellular dermal matrix allograft. Implant Dent. 2006, 15: 275-281. 10.1097/01.id.0000227078.70869.20.CrossRefPubMed Park JB: Increasing the width of keratinized mucosa around endosseous implant using acellular dermal matrix allograft. Implant Dent. 2006, 15: 275-281. 10.1097/01.id.0000227078.70869.20.CrossRefPubMed
38.
go back to reference Mahn DH: Aesthetic soft-tissue ridge augmentation. Dent Today. 2010, 96: 98-99. Mahn DH: Aesthetic soft-tissue ridge augmentation. Dent Today. 2010, 96: 98-99.
39.
go back to reference Becker J, Al-Nawas B, Klein MO, Schliephake H, Terheyden H, Schwarz F: Use of a new cross-linked collagen membrane for the treatment of dehiscence-type defects at titanium implants: a prospective, randomized-controlled double-blinded clinical multicenter study. Clin Oral Implants Res. 2009, 20: 742-749. 10.1111/j.1600-0501.2008.01689.x.CrossRefPubMed Becker J, Al-Nawas B, Klein MO, Schliephake H, Terheyden H, Schwarz F: Use of a new cross-linked collagen membrane for the treatment of dehiscence-type defects at titanium implants: a prospective, randomized-controlled double-blinded clinical multicenter study. Clin Oral Implants Res. 2009, 20: 742-749. 10.1111/j.1600-0501.2008.01689.x.CrossRefPubMed
Metadata
Title
Biodegradation pattern and tissue integration of native and cross-linked porcine collagen soft tissue augmentation matrices – an experimental study in the rat
Authors
Daniel Rothamel
Marcel Benner
Tim Fienitz
Arndt Happe
Matthias Kreppel
Hans-Joachim Nickenig
Joachim E Zöller
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Head & Face Medicine / Issue 1/2014
Electronic ISSN: 1746-160X
DOI
https://doi.org/10.1186/1746-160X-10-10

Other articles of this Issue 1/2014

Head & Face Medicine 1/2014 Go to the issue