CoChat
Sign Up
Cited by 282Bone Tissue Engineering MaterialsTissue Engineering and Regenerative MedicineHydrogels: synthesis, properties, applications

Hydrogels derived from demineralized and decellularized bone extracellular matrix

Open access
Sawkins, M.J., Bowen, W., Dhadda, P., Markides, H., Sidney, L.E., Taylor, A.J., Rose, F.R.A.J., Badylak, S.F. +2 more·2013·Acta Biomaterialia
DOI 10.1016/j.actbio.2013.04.029PMC PMC3711237
Open this paper in CoChat — free account

Abstract

The extracellular matrix (ECM) of mammalian tissues has been isolated, decellularized and utilized as a scaffold to facilitate the repair and reconstruction of numerous tissues. Recent studies have suggested that superior function and complex tissue formation occurred when ECM scaffolds were derived from site-specific homologous tissues compared with heterologous tissues. The objectives of the present study were to apply a stringent decellularization process to demineralized bone matrix (DBM), prepared from bovine bone, and to characterize the structure and composition of the resulting ECM materials and DBM itself. Additionally, we sought to produce a soluble form of DBM and ECM which could be induced to form a hydrogel. Current clinical delivery of DBM particles for treatment of bone defects requires incorporation of the particles within a carrier liquid. Differences in osteogenic activity, inflammation and nephrotoxicity have been reported with various carrier liquids. The use of hydrogel forms of DBM or ECM may reduce the need for carrier liquids. DBM and ECM hydrogels exhibited sigmoidal gelation kinetics consistent with a nucleation and growth mechanism, with ECM hydrogels characterized by lower storage moduli than the DBM hydrogels. Enhanced proliferation of mouse primary calvarial cells was achieved on ECM hydrogels, compared with collagen type I and DBM hydrogels. These results show that DBM and ECM hydrogels have distinct structural, mechanical and biological properties and have the potential for clinical delivery without the need for carrier liquids.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.actbio.2013.04.029

Cites

2 of 2 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • SDS-treated ECM scaffolds generally have higher reactivities upon implantation due to disruption of collagen fiber structures and exposure of cryptic antigens.

    “Of note, research has shown that SDS-treated ECM scaffolds generally have higher reactivities upon implantation due to the disruption of collagen fiber structures and exposure of cryptic antigens [7,59,94].”

    From Liver tissue engineering using decellularized scaffolds: Current progress, challenges, and opportunities (2024) · cites this paper as [94]

    The Materials and methods section describes decellularization with trypsin and EDTA, not SDS. The Discussion links trypsin to possible collagen disruption and separately discusses immune responses to α-Gal epitopes, but neither passage addresses higher implantation reactivity caused by SDS or exposure of cryptic antigens. Searches for SDS, sodium dodecyl sulphate, and cryptic antigens found no passage supporting that claim. (LLM, conf=0.74)

    Experimental — accuracy not yet measured

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Research works printed but not linked: 52

  1. [1]Badylak S.F. The extracellular matrix as a biologic scaffold material Biomaterials 28 2007 3587 3593 17524477
  2. [2]Badylak S.F. Kochupura P.V. Cohen I.S. Doronin S.V. Saltman A.E. Gilbert T.W. The use of extracellular matrix as an inductive scaffold for the partial replacement of functional myocardium Cell Transplant 15 2006 S29 S40 16826793
  3. [3]Quarti A. Nardone S. Colaneri M. Santoro G. Pozzi M. Preliminary experience in the use of an extracellular matrix to repair congenital heart diseases Interact Cardiovasc Thorac Surg 13 2011 569 572 21979987
  4. [4]Badylak S.F. Vorp D.A. Spievack A.R. Simmons-Byrd A. Hanke J. Freytes D.O. Esophageal reconstruction with ECM and muscle tissue in a dog model J Surg Res 128 2005 87 97 15922361
  5. [5]Turner N.J. Yates A.J. Weber D.J. Qureshi I.R. Stolz D.B. Gilbert T.W. Xenogeneic extracellular matrix as an inductive scaffold for regeneration of a functioning musculotendinous junction Tissue Eng Part A 16 2010 3309 3317 20528669
  6. [6]Valentin J.E. Turner N.J. Gilbert T.W. Badylak S.F. Functional skeletal muscle formation with a biologic scaffold Biomaterials 31 2010 7475 7484 20638716 PMC2922042
  7. [7]Badylak S.F. The extracellular matrix as a scaffold for tissue reconstruction Semin Cell Dev Biol 13 2002 377 383 12324220
  8. [9]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 Part A 15 2009 1119 1125 18837648 PMC2789572
  9. [10]Reing J.E. Zhang L. Myers-Irvin J. Cordero K.E. Freytes D.O. Heber-Katz E. Degradation products of extracellular matrix affect cell migration and proliferation Tissue Eng Part A 15 2009 605 614 18652541
  10. [11]Vorotnikova E. McIntosh D. Dewilde A. Zhang J. Reing J.E. Zhang L. Extracellular matrix-derived products modulate endothelial and progenitor cell migration and proliferation in vitro and stimulate regenerative healing in vivo Matrix Biol. 29 2010 690 700 20797438
  11. [12]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 88 2006 2673 2686 17142418
  12. [14]Sellaro T.L. Ranade A. Faulk D.M. McCabe G.P. Dorko K. Badylak S.F. Maintenance of human hepatocyte function in vitro by liver-derived extracellular matrix gels Tissue Eng Part A 16 2010 1075 1082 19845461 PMC2863084
  13. [15]Cortiella J. Niles J. Cantu A. Brettler A. Pham A. Vargas G. Influence of acellular natural lung matrix on murine embryonic stem cell differentiation and tissue formation Tissue Eng Part A 16 2010 2565 2580 20408765
  14. [16]Petersen T.H. Calle E.A. Zhao L. Lee E.J. Gui L. Raredon M.B. Tissue-engineered lungs for in vivo implantation Science 329 2010 538 541 20576850 PMC3640463
  15. [17]Uygun B.E. Soto-Gutierrez A. Yagi H. Izamis M.-L. Guzzardi M.A. Shulman C. Organ reengineering through development of a transplantable recellularized liver graft using decellularized liver matrix Nat Med 16 2010 814 820 20543851 PMC2930603
  16. [18]Woolf A.D. Pfleger B. Burden of major musculoskeletal conditions Bull World Health Organ 81 2003 646 656 14710506 PMC2572542
  17. [20]Evaluation criteria for musculoskeletal and craniofacial tissue engineering constructs: a conference report. Tissue Eng Part A 2008;14:2089–2104. PMC2809981 19093294
  18. [21]Dinopoulos H. Dimitriou R. Giannoudis P.V. Bone graft substitutes: what are the options? The Surgeon 10 2012 230 239 22682580
  19. [22]Guldberg R.E. Spatiotemporal delivery strategies for promoting musculoskeletal tissue regeneration J Bone Miner Res 24 2009 1507 1511 19653806
  20. [23]Greenwald A.S. Boden S.D. Goldberg V.M. Khan Y. Laurencin C.T. Rosier R.N. Bone-graft substitutes: facts, fictions, and applications J Bone Joint Surg 83 2001 S98 S103 11712842
  21. [24]Peterson B. Whang P.G. Iglesias R. Wang J.C. Lieberman J.R. Osteoinductivity of commercially available demineralized bone matrix preparations in a spine fusion model J Bone Joint Surg 86 2004 2243 2250 15466734
  22. [25]Wang J.C. Alanay A. Mark D. Kanim L.E. Campbell P.A. Dawson E.G. A comparison of commercially available demineralized bone matrix for spinal fusion Eur Spine J 16 2007 1233 1240 17205237 PMC2200779
  23. [26]De Long W.G. Einhorn T.A. Koval K. McKee M. Smith W. Sanders R. Bone grafts and bone graft substitutes in orthopaedic trauma surgery: a critical analysis J Bone Joint Surg 89 2007 649 658 17332116
  24. [27]Gruskin E. Doll B.A. Futrell F.W. Schmitz J.P. Hollinger J.O. Demineralized bone matrix in bone repair: history and use Adv Drug Deliv Rev 64 2012 1063 1077 22728914 PMC7103314
  25. [28]Bostrom M.P. Yang X. Kennan M. Sandhu H. Dicarlo E. Lane J.M. An unexpected outcome during testing of commercially available demineralized bone graft materials: how safe are the nonallograft components? Spine (Phila Pa 1976) 26 2001 1425 1428 11458144
  26. [29]Acarturk T.O. Hollinger J.O. Commercially available demineralized bone matrix compositions to regenerate calvarial critical-sized bone defects Plast Reconstr Surg 118 2006 862 873 16980846
  27. [30]Markel D.C. Guthrie S.T. Wu B. Song Z. Wooley P.H. Characterization of the inflammatory response to four commercial bone graft substitutes using a murine biocompatibility model J Inflamm Res 5 2012 13 18 22334792 PMC3278258
  28. [31]Yazdi M. Bernick S. Paule W.J. Nimni M.E. Postmortem degradation of demineralized bone matrix osteoinductive potential. Effect of time and storage temperature Clin Orthop Relat Res 262 1991 281 285 1984927
  29. [32]Lomas R.J. Gillan H.L. Matthews J.B. Ingham E. Kearney J.N. An evaluation of the capacity of differently prepared demineralised bone matrices (DBM) and toxic residuals of ethylene oxide (EtOx) to provoke an inflammatory response in vitro Biomaterials 22 2001 913 921 11311010
  30. [33]Pietrzak W.S. Ali S.N. Chitturi D. Jacob M. Woodell-May J.E. BMP depletion occurs during prolonged acid demineralization of bone: characterization and implications for graft preparation Cell Tissue Bank 12 2011 81 88 20039143
  31. [34]Schenke-Layland K. Vasilevski O. Opitz F. König K. Riemann I. Halbhuber K.J. Impact of decellularization of xenogeneic tissue on extracellular matrix integrity for tissue engineering of heart valves J Struct Biol 143 2003 201 208 14572475
  32. [35]Hong Y. Huber A. Takanari K. Amoroso N.J. Hashizume R. Badylak S.F. Mechanical properties and in vivo behavior of a biodegradable synthetic polymer microfiber – extracellular matrix hydrogel biohybrid scaffold Biomaterials 32 2011 3387 3394 21303718 PMC3184831
  33. [36]Gilbert T.W. Freund J.M. Badylak S.F. Quantification of DNA in biologic scaffold materials J Surg Res 152 2009 135 139 18619621 PMC2783373
  34. [37]Keane T.J. Londono R. Turner N.J. Badylak S.F. Consequences of ineffective decellularization of biologic scaffolds on the host response Biomaterials 33 2012 1771 1781 22137126
  35. [38]Woessner J.F. The determination of hydroxyproline in tissue and protein samples containing small proportions of this imino acid Arch Biochem Biophys 93 1961 440 447 13786180
  36. [39]Freytes D.O. Martin J. Velankar S.S. Lee A.S. Badylak S.F. Preparation and rheological characterization of a gel form of the porcine urinary bladder matrix Biomaterials 29 2008 1630 1637 18201760
  37. [40]Wolf M.T. Daly K.A. Brennan-Pierce E.P. Johnson S.A. Carruthers C.A. D’Amore A. A hydrogel derived from decellularized dermal extracellular matrix Biomaterials 33 2012 7028 7038 22789723 PMC3408574
  38. [41]Reing J.E. Brown B.N. Daly K.A. Freund J.M. Gilbert T.W. Hsiong S.X. The effects of processing methods upon mechanical and biologic properties of porcine dermal extracellular matrix scaffolds Biomaterials 31 2010 8626 8633 20728934 PMC2956268
  39. [42]Crapo P.M. Gilbert T.W. Badylak S.F. An overview of tissue and whole organ decellularization processes Biomaterials 32 2011 3233 3243 21296410 PMC3084613
  40. [43]Wood G.C. The formation of fibrils from collagen solutions. 2. A mechanism of collagen-fibril formation Biochem J 75 1960 598 605 13845810 PMC1204516
  41. [44]Wood G.C. Keech M.K. The formation of fibrils from collagen solutions. 1. The effect of experimental conditions: kinetic and electron-microscope studies Biochem J 75 1960 588 598 13845809 PMC1204515
  42. [45]Brightman A.O. Rajwa B.P. Sturgis J.E. McCallister M.E. Robinson J.P. Voytik-Harbin S.L. Time-lapse confocal reflection microscopy of collagen fibrillogenesis and extracellular matrix assembly in vitro Biopolymers 54 2000 222 234 10861383
  43. [46]Y.-l. Yang. Kaufman L.J. Rheology and confocal reflectance microscopy as probes of mechanical properties and structure during collagen and collagen/hyaluronan self-assembly Biophys J 96 2009 1566 1585 19217873 PMC2717242
  44. [47]Stuart K. Panitch A. Influence of chondroitin sulfate on collagen gel structure and mechanical properties at physiologically relevant levels Biopolymers 89 2008 841 851 18488988
  45. [48]Yang M. Chen C.Z. Wang X.N. Zhu Y.B. Gu Y.J. Favorable effects of the detergent and enzyme extraction method for preparing decellularized bovine pericardium scaffold for tissue engineered heart valves J Biomed Mater Res B Appl Biomater 91 2009 354 361 19507136
  46. [49]DeQuach J.A. Lin J.E. Cam C. Hu D. Salvatore M.A. Sheikh F. Injectable skeletal muscle matrix hydrogel promotes neovascularization and muscle cell infiltration in a hindlimb ischemia model Eur Cell Mater 23 2012 400 412 22665162 PMC3524267
  47. [50]Badylak S.F. Gilbert T.W. Immune response to biologic scaffold materials Semin Immunol 20 2008 109 116 18083531 PMC2605275
  48. [51]Galili U. The [alpha]-gal epitope and the anti-Gal antibody in xenotransplantation and in cancer immunotherapy Immunol Cell Biol 83 2005 674 686 16266320
  49. [52]Raeder R.H. Badylak S.F. Sheehan C. Kallakury B. Metzger D.W. Natural anti-galactose α1,3 galactose antibodies delay, but do not prevent the acceptance of extracellular matrix xenografts Transpl Immunol 10 2002 15 24 12182460
  50. [53]Daly K.A. Stewart-Akers A.M. Hara H. Ezzelarab M. Long C. Cordero K. Effect of the αGal epitope on the response to small intestinal submucosa extracellular matrix in a nonhuman primate model Tissue Eng Part A 15 2009 3877 3888 19563260
  51. [54]Yoshida R. Vavken P. Murray M.M. Decellularization of bovine anterior cruciate ligament tissues minimizes immunogenic reactions to alpha-gal epitopes by human peripheral blood mononuclear cells Knee 19 2012 672 675 21925883 PMC3243811
  52. [55]Hadjipanayi E. Mudera V. Brown R.A. Close dependence of fibroblast proliferation on collagen scaffold matrix stiffness J Tissue Eng Regen Med 3 2009 77 84 19051218

Cited by

Sorted by citations

Authors
Sawkins, M. J., Bowen, W., Dhadda, P., Markides, H., Sidney, L. E., Taylor, A. J., Rose, F. R. A. J., Badylak, S. F., Shakesheff, K. M., & White, L. J.
Affiliations
  • University of Nottingham (GB)
  • University of Pittsburgh (US)
Corresponding author
White, L.J.
ORCID
Venue
Acta Biomaterialia
Publisher
Elsevier BV
Published
2013-08
Volume
9
Issue
8
Pages
7865-7873
ISSN
1742-7061 (ISSN-L)
DOI
10.1016/j.actbio.2013.04.029
PMC
PMC3711237
OpenAlex
W2120689844
Cited by
282
References
2
Citations by year
2026: 12 · 2025: 21 · 2024: 23 · 2023: 20 · 2022: 33 · 2021: 27 · 2020: 30 · 2019: 27 · 2018: 28 · 2017: 21 · 2016: 12 · 2015: 18 · 2014: 9 · 2013: 1
FWCI
7.36
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Acta Biomaterialia (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion)
  • PubMed Central (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • EPSRC Centre for Innovative Manufacturing in Regenerative Medicine (ECP038/0512)
  • Biotechnology and Biological Sciences Research Council (BBSRC), UK (BB/G010617/1)
  • European Research Council
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
Keywords
demineralized bone matrix, decellularized extracellular matrix, hydrogels, gelation kinetics, nucleation and growth, storage modulus, mechanical properties, bone defects, carrier liquid, bovine bone, type I collagen, tissue engineering scaffolds
MeSH terms
Animals, Cattle, Cell-Free System, Cells, Cultured, Extracellular Matrix, Materials Testing, Minerals, Tibia, Bone Substitutes, Hydrogels

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review