Macrophage Participation in the Degradation and Remodeling of Extracellular Matrix Scaffolds
Open accessAbstract
Biologic scaffolds composed of extracellular matrix (ECM) are widely used to facilitate remodeling and reconstruction of a variety of tissues in both preclinical animal studies and human clinical applications. The mechanisms by which such scaffolds influence the host tissue response are only partially understood, but it is logical that the mononuclear macrophage cell population plays a central role. The present study evaluated the role of macrophages that derive from peripheral blood in the degradation of ECM scaffolds. An established rat body wall reconstruction model was used to evaluate the degradation of carbodiimide (CDI)-crosslinked scaffolds composed of porcine small intestinal submucosa (SIS), noncrosslinked SIS, and autologous body wall. To assess the role of circulating macrophages in the degradation process, the degradation of each scaffold was assessed with and without macrophage depletion caused by administration of clodronate-containing liposomes. Results showed that peripheral blood monocytes are required for the early and rapid degradation of both SIS scaffolds and autologous body wall, and that CDI crosslinked SIS is resistant to macrophage-mediated degradation.
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This constructive remodeling response is directly linked to the material's ability to modulate macrophage phenotype.
“This constructive remodeling response has been directly linked to the ability of the material to modulate macrophage phenotype [154–157].”
From Macrophage polarization: an opportunity for improved outcomes in biomaterials and regenerative medicine (2012) · cites this paper as [157]
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- [1]Chen F. Yoo J.J. Atala A. Acellular collagen matrix as a possible “off the shelf ” biomaterial for urethral repair. Urology. 1999;54:407. doi: 10.1016/s0090-4295(99)00179-x. [DOI] [PubMed] [Google Scholar] · DOI
- [2]Hodde J. Naturally occurring scaffolds for soft tissue repair and regeneration. Tissue Eng. 2002;8:295. doi: 10.1089/107632702753725058. [DOI] [PubMed] [Google Scholar] · DOI
- [3]Hodde J.P. Record R.D. Liang H.A. Badylak S.F. Vascular endothelial growth factor in porcine-derived extracellular matrix. Endothelium. 2001;8:11. doi: 10.3109/10623320109063154. [DOI] [PubMed] [Google Scholar] · DOI
- [4]Li F. Li W. Johnson S. Ingram D. Yoder M. Badylak S.F. Low-molecular-weight peptides derived from extracellular matrix as chemoattractants for primary endothelial cells. Endothelium. 2004;11:199. doi: 10.1080/10623320490512390. [DOI] [PubMed] [Google Scholar] · DOI
- [5]Nieponice A. Gilbert T.W. Badylak S.F. Reinforcement of esophageal anastomoses with an extracellular matrix scaffold in a canine model. Ann Thorac Surg. 2006;82:2050. doi: 10.1016/j.athoracsur.2006.06.036. [DOI] [PubMed] [Google Scholar] · DOI
- [6]Badylak S.F. Park K. Peppas N. McCabe G. Yoder M. Marrow-derived cells populate scaffolds composed of xenogeneic extracellular matrix. Exp Hematol. 2001;29:1310. doi: 10.1016/s0301-472x(01)00729-9. [DOI] [PubMed] [Google Scholar] · DOI
- [7]Beattie A.J. Gilbert T.W. Guyot J.P. Yates A.J. Badylak S.F. Chemoattraction of progenitor cells by remodeling extracellular matrix scaffolds. Tissue Eng doi: 10.1089/ten.tea.2008.0162. 2008 doi: 10.1089/ten.tea.2008.0162. No additional information is available. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [8]Reing J.E. Zhang L. Myers-Irvin J. Cordero K.E. Freytes D.O. Heber-Katz E. Bedelbaeva K. McIntosh D. Dewilde A. Braunhut S.J. Badylak S.F. Degradation products of extracellular matrix affect cell migration and proliferation. Tissue Eng Part A doi: 10.1089/ten.tea.2007.0425. 2008 doi: 10.1089/ten.tea.2007.0425. No additional information is available. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
- [9]Zantop T. Gilbert T.W. Yoder M.C. Badylak S.F. Extracellular matrix scaffolds are repopulated by bone marrow-derived cells in a mouse model of Achilles tendon reconstruction. J Orthop Res. 2006;24:1299. doi: 10.1002/jor.20071. [DOI] [PubMed] [Google Scholar] · DOI
- [10]Badylak S.F. Coffey A.C. Lantz G.C. Tacker W.A. Geddes L.A. Comparison of the resistance to infection of intestinal submucosa arterial autografts versus polytetrafluoroethylene arterial prostheses in a dog model. J Vasc Surg. 1994;19:465. doi: 10.1016/s0741-5214(94)70073-7. [DOI] [PubMed] [Google Scholar] · DOI
- [11]Badylak S.F. Wu C.C. Bible M. McPherson E. Host protection against deliberate bacterial contamination of an extracellular matrix bioscaffold versus Dacron mesh in a dog model of orthopedic soft tissue repair. J Biomed Mater Res B Appl Biomater. 2003;67:648. doi: 10.1002/jbm.b.10062. [DOI] [PubMed] [Google Scholar] · DOI
- [12]Brennan E.P. Reing J. Chew D. Myers-Irvin J.M. Young E.J. Badylak S.F. Antibacterial activity within degradation products of biological scaffolds composed of extracellular matrix. Tissue Eng. 2006;12:2949. doi: 10.1089/ten.2006.12.2949. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [13]Jernigan T.W. Croce M.A. Cagiannos C. Shell D.H. Handorf C.R. Fabian T.C. Small intestinal submucosa for vascular reconstruction in the presence of gastrointestinal contamination. Ann Surg. 2004;239:733. doi: 10.1097/01.sla.0000124447.30808.c7. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [14]Sarikaya A. Record R. Wu C.C. Tullius B. Badylak S.F. Ladisch M. Antimicrobial activity associated with extracellular matrices. Tissue Eng. 2002;8:63. doi: 10.1089/107632702753503063. [DOI] [PubMed] [Google Scholar] · DOI
- [16]Allman A.J. McPherson T.B. Badylak S.F. Merrill L.C. Kallakury B. Sheehan C. Raeder R.H. Metzger D.W. Xenogeneic extracellular matrix grafts elicit a TH2-restricted immune response. Transplantation. 2001;71:1631. doi: 10.1097/00007890-200106150-00024. [DOI] [PubMed] [Google Scholar] · DOI · Paper page
- [17]Badylak S.F. Gilbert T.W. Immune response to biologic scaffold materials. Semin Immunol. 2008;20:109. doi: 10.1016/j.smim.2007.11.003. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI · Paper page
- [19]Hodde J. Janis A. Hiles M. Effects of sterilization on an extracellular matrix scaffold: part II. Bioactivity and matrix interaction. J Mater Sci Mater Med. 2007;18:545. doi: 10.1007/s10856-007-2301-9. [DOI] [PubMed] [Google Scholar] · DOI
- [20]Whitlock P.W. Smith T.L. Poehling G.G. Shilt J.S. van Dyke M. A naturally derived, cytocompatible, and architecturally optimized scaffold for tendon and ligament regeneration. Biomaterials. 2007;28:4321. doi: 10.1016/j.biomaterials.2007.05.029. [DOI] [PubMed] [Google Scholar] · DOI
- [21]Gilbert T.W. Stewart-Akers A.M. Simmons-Byrd A. Badylak S.F. Degradation and remodeling of small intestinal submucosa in canine Achilles tendon repair. J Bone Joint Surg Am. 2007;89:621. doi: 10.2106/JBJS.E.00742. [DOI] [PubMed] [Google Scholar] · DOI
- [22]Record R.D. Hillegonds D. Simmons C. Tullius R. Rickey F.A. Elmore D. Badylak S.F. In vivo degradation of 14C-labeled small intestinal submucosa (SIS) when used for urinary bladder repair. Biomaterials. 2001;22:2653. doi: 10.1016/s0142-9612(01)00007-2. [DOI] [PubMed] [Google Scholar] · DOI
- [23]Valentin J.E. Badylak J.S. McCabe G.P. Badylak S.F. Extracellular matrix bioscaffolds for orthopaedic applications. A comparative histologic study. J Bone Joint Surg Am. 2006;88:2673. doi: 10.2106/JBJS.E.01008. [DOI] [PubMed] [Google Scholar] · DOI
- [24]Billiar K. Murray J. Laude D. Abraham G. Bachrach N. Effects of carbodiimide crosslinking conditions on the physical properties of laminated intestinal submucosa. J Biomed Mater Res. 2001;56:101. doi: 10.1002/1097-4636(200107)56:1<101::aid-jbm1074>3.0.co;2-6. [DOI] [PubMed] [Google Scholar] · DOI
- [25]Coons D.A. Alan Barber F. Tendon graft substitutes-rotator cuff patches. Sports Med Arthrosc. 2006;14:185. doi: 10.1097/00132585-200609000-00011. [DOI] [PubMed] [Google Scholar] · DOI
- [26]Metcalf M.H. Savoie F.H. Kellum B. Surgical technique for xenograft (SIS) augmentation of rotator-cuff repairs. Oper Tech Orthop. 2002;12:204. [Google Scholar]
- [27]van Rooijen N. Sanders A. Liposome mediated depletion of macrophages: mechanism of action, preparation of liposomes and applications. J Immunol Methods. 1994;174:83. doi: 10.1016/0022-1759(94)90012-4. [DOI] [PubMed] [Google Scholar] · DOI
- [28]van Rooijen N. Sanders A. Elimination, blocking, and activation of macrophages: three of a kind? J Leukoc Biol. 1997;62:702. doi: 10.1002/jlb.62.6.702. [DOI] [PubMed] [Google Scholar] · DOI
- [29]van Rooijen N. Sanders A. van den Berg T.K. Apoptosis of macrophages induced by liposome-mediated intracellular delivery of clodronate and propamidine. J Immunol Methods. 1996;193:93. doi: 10.1016/0022-1759(96)00056-7. [DOI] [PubMed] [Google Scholar] · DOI
- [30]Gilbert T.W. Stewart-Akers A.M. Badylak S.F. A quantitative method for evaluating the degradation of biologic scaffold materials. Biomaterials. 2007;28:147. doi: 10.1016/j.biomaterials.2006.08.022. [DOI] [PubMed] [Google Scholar] · DOI
- [31]Freytes D.O. Badylak S.F. Webster T.J. Geddes L.A. Rundell A.E. Biaxial strength of multilaminated extracellular matrix scaffolds. Biomaterials. 2004;25:2353. doi: 10.1016/j.biomaterials.2003.09.015. [DOI] [PubMed] [Google Scholar] · DOI
- [32]Hafemann B. Ghofrani K. Gattner H.G. Stieve H. Pallua N. Cross-linking by 1-ethyl-3- (3-dimethylaminopropyl)-carbodiimide (EDC) of a collagen/elastin membrane meant to be used as a dermal substitute: effects on physical, biochemical and biological features in vitro. J Mater Sci Mater Med. 2001;12:437. doi: 10.1023/a:1011205221972. [DOI] [PubMed] [Google Scholar] · DOI
- [33]Kim M.S. Hong K.D. Shin H.W. Kim S.H. Lee M.S. Jang W.Y. Khang G. Lee H.B. Preparation of porcine small intestinal submucosa sponge and their application as a wound dressing in full-thickness skin defect of rat. Int J Biol Macromol. 2005;36:54. doi: 10.1016/j.ijbiomac.2005.03.013. [DOI] [PubMed] [Google Scholar] · DOI
- [34]Markowicz M.P. Steffens G.C. Fuchs P.C. Pallua N. Enhanced dermal regeneration using modified collagen scaffolds: experimental porcine study. Int J Artif Organs. 2006;29:1167. doi: 10.1177/039139880602901210. [DOI] [PubMed] [Google Scholar] · DOI
- [35]van Rooijen N. van Kesteren-Hendrikx E. “In vivo” depletion of macrophages by liposome-mediated “suicide”. Methods Enzymol. 2003;373:3. doi: 10.1016/s0076-6879(03)73001-8. [DOI] [PubMed] [Google Scholar] · DOI
- [36]Frid M.G. Brunetti J.A. Burke D.L. Carpenter T.C. Davie N.J. Reeves J.T. Roedersheimer M.T. van Rooijen N. Stenmark K.R. Hypoxia-induced pulmonary vascular remodeling requires recruitment of circulating mesenchymal precursors of a monocyte/macrophage lineage. Am J Pathol. 2006;168:659. doi: 10.2353/ajpath.2006.050599. [DOI] [PMC free article] [PubMed] [Google Scholar] · DOI
- [37]Badylak S.F. Vorp D.A. Spievack A.R. Simmons-Byrd A. Hanke J. Freytes D.O. Thapa A. Gilbert T.W. Nieponice A. Esophageal reconstruction with ECM and muscle tissue in a dog model. J Surg Res. 2005;128:87. doi: 10.1016/j.jss.2005.03.002. [DOI] [PubMed] [Google Scholar] · DOI
- [38]Kropp B.P. Sawyer B.D. Shannon H.E. Rippy M.K. Badylak S.F. Adams M.C. Keating M.A. Rink R.C. Thor K.B. Characterization of small intestinal submucosa regenerated canine detrusor: assessment of reinnervation, in vitro compliance and contractility. J Urol. 1996;156:599. doi: 10.1097/00005392-199608001-00008. [DOI] [PubMed] [Google Scholar] · DOI
- [39]Hodde J.P. Ernst D.M. Hiles M.C. An investigation of the long-term bioactivity of endogenous growth factor in OASIS wound matrix. J Wound Care. 2005;14:23. doi: 10.12968/jowc.2005.14.1.26721. [DOI] [PubMed] [Google Scholar] · DOI
- [40]McDevitt C.A. Wildey G.M. Cutrone R.M. Transforming growth factor-beta1 in a sterilized tissue derived from the pig small intestine submucosa. J Biomed Mater Res A. 2003;67:637. doi: 10.1002/jbm.a.10144. [DOI] [PubMed] [Google Scholar] · DOI
- [41]Voytik-Harbin S.L. Brightman A.O. Kraine M.R. Waisner B. Badylak S.F. Identification of extractable growth factors from small intestinal submucosa. J Cell Biochem. 1997;67:478. [PubMed] [Google Scholar]
- [42]Reing J.E. Zhang L. Myers-Irvin J. Cordero K.E. Freytes D.O. Heber-Katz E. Bedelbaeva K. McIntosh D. Dewilde A. Braunhut S.J. Badylak S.F. Degradation products of extracellular matrix affect cell migration and proliferation. Tissue Eng. 2008 doi: 10.1089/ten.tea.2007.0425. (In press). [DOI] [PubMed] [Google Scholar] · DOI · Paper page
- [43]Badylak S.F. Kokini K. Tullius B. Simmons-Byrd A. Morff R. Morphologic study of small intestinal submucosa as a body wall repair device. J Surg Res. 2002;103:190. doi: 10.1006/jsre.2001.6349. [DOI] [PubMed] [Google Scholar] · DOI
- [44]Zheng M.H. Chen J. Kirilak Y. Willers C. Xu J. Wood D. Porcine small intestine submucosa (SIS) is not an acellular collagenous matrix and contains porcine DNA: possible implications in human implantation. J Biomed Mater Res B Appl Biomater. 2005;73:61. doi: 10.1002/jbm.b.30170. [DOI] [PubMed] [Google Scholar] · DOI
- [45]Badylak S.F. Arnoczky S. Plouhar P. Haut R. Mendenhall V. Clarke R. Horvath C. Naturally occurring extracellular matrix as a scaffold for musculoskeletal repair. Clin Orthop. 1999;367 Suppl:S333. doi: 10.1097/00003086-199910001-00032. [DOI] [PubMed] [Google Scholar] · DOI
- [46]Badylak S.F. Kochupura P.V. Cohen I.S. Doronin S.V. Saltman A.E. Gilbert T.W. Kelly D.J. Ignotz R.A. Gaudette G.R. The use of extracellular matrix as an inductive scaffold for the partial replacement of functional myocardium. Cell Transplant. 2006;15 Suppl 1:S29. doi: 10.3727/000000006783982368. [DOI] [PubMed] [Google Scholar] · DOI
- [47]Badylak S.F. Kokini K. Tullius B. Whitson B. Strength over time of a resorbable bioscaffold for body wall repair in a dog model. J Surg Res. 2001;99:282. doi: 10.1006/jsre.2001.6176. [DOI] [PubMed] [Google Scholar] · DOI
- [48]Dejardin L.M. Arnoczky S.P. Ewers B.J. Haut R.C. Clarke R.B. Tissue-engineered rotator cuff tendon using porcine small intestine submucosa. Histologic and mechanical evaluation in dogs. Am J Sports Med. 2001;29:175. doi: 10.1177/03635465010290021001. [DOI] [PubMed] [Google Scholar] · DOI
- [49]Harper C. Permacol: clinical experience with a new biomaterial. Hosp Med. 2001;62:90. doi: 10.12968/hosp.2001.62.2.2379. [DOI] [PubMed] [Google Scholar] · DOI
- [50]Kim K.M. Cells, rather than extracellular matrix, nucleate apatite in glutaraldehyde-treated vascular tissue. J Biomed Mater Res. 2002;59:639. doi: 10.1002/jbm.10038. [DOI] [PubMed] [Google Scholar] · DOI
- [51]Valente M. Laborde F. Thiene G. Milano A. Talenti E. Gallix P. Glutaraldehyde-fixed bovine iliac veins used as bioprosthetic conduits: an experimental animal study. J Card Surg. 1992;7:156. doi: 10.1111/j.1540-8191.1992.tb00791.x. [DOI] [PubMed] [Google Scholar] · DOI
- [52]Hsu S.Y. Cheng J.C. Chong Y.W. Leung P.C. Glutaraldehyde-treated bioprosthetic substitute for rabbit Achilles tendon. Biomaterials. 1989;10:258. doi: 10.1016/0142-9612(89)90102-6. [DOI] [PubMed] [Google Scholar] · DOI
- [53]Ueno T. Pickett L.C. de la Fuente S.G. Lawson D.C. Pappas T.N. Clinical application of porcine small intestinal submucosa in the management of infected or potentially contaminated abdominal defects. J Gastrointest Surg. 2004;8:109. doi: 10.1016/j.gassur.2003.09.025. [DOI] [PubMed] [Google Scholar] · DOI
- Authors
- Valentin, J. E., Stewart-Akers, A. M., Gilbert, T. W., & Badylak, S. F.
- Affiliations
- University of Pittsburgh (US)
- Department of Surgery, McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania.
- Corresponding author
- Badylak, Stephen F.
- Venue
- Tissue Engineering Part A
- Publisher
- SAGE Publications
- Published
- 2009-07
- Volume
- 15
- Issue
- 7
- Pages
- 1687-1694
- ISSN
- 1937-3341 (ISSN-L)
- 1937-335X
- PMC
- PMC2792102
- OpenAlex
- W2053475436
- Cited by
- 356
- References
- 54
- Citations by year
- 2026: 7 · 2025: 15 · 2024: 14 · 2023: 13 · 2022: 18 · 2021: 29 · 2020: 15 · 2019: 19 · 2018: 18 · 2017: 31 · 2016: 21 · 2015: 29 · 2014: 34 · 2013: 30 · 2012: 20
- FWCI
- 20.95
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Tissue Engineering Part A (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Institute of Biomedical Imaging and Bioengineering (EB007678-01)
- Topics
- Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
- Health Sciences › Medicine › Rehabilitation › Wound Healing and Treatments
- Physical Sciences › Materials Science › Biomaterials › Electrospun Nanofibers in Biomedical Applications
- Keywords
- macrophages, extracellular matrix scaffolds, scaffold degradation, tissue remodeling, small intestinal submucosa, carbodiimide crosslinking, clodronate liposomes, macrophage depletion, peripheral blood monocytes, host tissue response
- MeSH terms
- CD68 Molecule, Animals, Carbodiimides, Cross-Linking Reagents, Extracellular Matrix, Fluorescent Antibody Technique, Immunohistochemistry, Intestinal Mucosa, Macrophages, Male, Postoperative Care, Transplantation, Autologous, Antigens, Differentiation, Myelomonocytic, Antigens, CD, Prosthesis Implantation, Sus scrofa, Rats, Tissue Scaffolds
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