In vitro and in vivo comparison of five biomaterials used for orthopedic soft tissue augmentation

James L. Cook Comparative Orthopaedic Laboratory, University of Missouri, Columbia, MO 65211.

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Derek B. Fox Comparative Orthopaedic Laboratory, University of Missouri, Columbia, MO 65211.

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Keiichi Kuroki Comparative Orthopaedic Laboratory, University of Missouri, Columbia, MO 65211.

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Manuel Jayo Tengion Laboratories, 3929 Westpoint Blvd, Winston-Salem, NC 27103.

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Patrick G. De Deyne DePuy Spine, 325 Paramount Dr, Raynham, MA 02767.

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 MPT, PhD

Abstract

Objective—To compare biomaterials used in orthopedics with respect to in vitro cell viability and cell retention and to in vivo tissue healing and regeneration.

Animals—65 adult female Sprague-Dawley rats and synovium, tendon, meniscus, and bone marrow specimens obtained from 4 adult canine cadavers.

Procedures—Synovium, tendon, meniscus, and bone marrow specimens were used to obtain synovial fibroblasts, tendon fibroblasts, meniscal fibrochondrocytes, and bone marrow–derived connective tissue progenitor cells for culture on 5 biomaterials as follows: cross-linked porcine small intestine (CLPSI), non–cross-linked human dermis, cross-linked porcine dermis, non–cross-linked porcine small intestine (NCLPSI), and non–cross-linked fetal bovine dermis. After 1 week of culture, samples were evaluated for cell viability, cell density, and extracellular matrix production. Biomaterials were evaluated in a 1-cm2 abdominal wall defect in rats. Each biomaterial was subjectively evaluated for handling, suturing, defect fit, and ease of creating the implant at the time of surgery, then grossly and histologically 6 and 12 weeks after surgery.

Results—All biomaterials allowed for retention of viable cells in culture; however, CLPSI and NCLPSI were consistently superior in terms of cell viability and cell retention. Cell infiltration for NCLPSI was superior to other biomaterials. The NCLPSI appeared to be replaced with regenerative tissue most rapidly in vivo and scored highest in all subjective evaluations of ease of use.

Conclusions and Clinical Relevance—These data suggested that NCLPSI and CLPSI have favorable properties for further investigation of clinical application in orthopedic tissue engineering.

Abstract

Objective—To compare biomaterials used in orthopedics with respect to in vitro cell viability and cell retention and to in vivo tissue healing and regeneration.

Animals—65 adult female Sprague-Dawley rats and synovium, tendon, meniscus, and bone marrow specimens obtained from 4 adult canine cadavers.

Procedures—Synovium, tendon, meniscus, and bone marrow specimens were used to obtain synovial fibroblasts, tendon fibroblasts, meniscal fibrochondrocytes, and bone marrow–derived connective tissue progenitor cells for culture on 5 biomaterials as follows: cross-linked porcine small intestine (CLPSI), non–cross-linked human dermis, cross-linked porcine dermis, non–cross-linked porcine small intestine (NCLPSI), and non–cross-linked fetal bovine dermis. After 1 week of culture, samples were evaluated for cell viability, cell density, and extracellular matrix production. Biomaterials were evaluated in a 1-cm2 abdominal wall defect in rats. Each biomaterial was subjectively evaluated for handling, suturing, defect fit, and ease of creating the implant at the time of surgery, then grossly and histologically 6 and 12 weeks after surgery.

Results—All biomaterials allowed for retention of viable cells in culture; however, CLPSI and NCLPSI were consistently superior in terms of cell viability and cell retention. Cell infiltration for NCLPSI was superior to other biomaterials. The NCLPSI appeared to be replaced with regenerative tissue most rapidly in vivo and scored highest in all subjective evaluations of ease of use.

Conclusions and Clinical Relevance—These data suggested that NCLPSI and CLPSI have favorable properties for further investigation of clinical application in orthopedic tissue engineering.

Contributor Notes

Supported by DePuy Orthopaedics Incorporated, a Johnson & Johnson Company.

Drs. Cook, Fox, and Jayo were paid consultants for DePuy during the study period.

Address correspondence to Dr. Cook.
  • 1.

    Cook JL, Kreeger JM, Payne JT, et al. Three-dimensional culture of canine articular chondrocytes on multiple transplantable substrates. Am J Vet Res 1997;58:419424.

    • Search Google Scholar
    • Export Citation
  • 2.

    Cook JL, Fox DB, Malaviya P, et al. Evaluation of small intestinal submucosa grafts for meniscal regeneration in a clinicallyrelevant posterior meniscectomy model in dogs. J Knee Surg 2006;19:159167.

    • Search Google Scholar
    • Export Citation
  • 3.

    Cook JL, Fox DB, Malaviya P, et al. Long-term evaluation of treatment of large meniscal defects using small intestinal submucosa in a dog model. Am J Sports Med 2006;34:3242.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 4.

    Cook JL. The current status of treatment for large meniscal defects. Clin Orthop Relat Res 2005;435:8895.

  • 5.

    Fox DB, Cook JL, Arnoczky SP, et al. Fibrochondrogenesis of free intra-articular small intestinal submucosa scaffolds. Tissue Eng 2004;10:129137.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 6.

    Cook JL, Tomlinson JL, Arnoczky SP, et al. Kinetic study of the replacement of porcine small intestinal submucosa grafts and the regeneration of meniscal-like tissue in large avascular meniscal defects in dogs. Tissue Eng 2001;7:321334.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 7.

    Cook JL, Tomlinson JL, Kreeger JM, et al. Induction of meniscal regeneration in dogs using a novel biomaterial. Am J Sports Med 1999;27:658665.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 8.

    Rodkey WG, Steadman JR, Li ST. A clinical study of collagen meniscus implants to restore the injured meniscus. Clin Orthop 1999;367:S281S292.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 9.

    Stone KR, Steadman JR, Rodkey WG, et al. Regeneration of meniscal cartilage with use of a collagen scaffold. Analysis of preliminary data. J Bone Joint Surg Am 1997;79:17701777.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 10.

    Dejardin LM, Arnoczky SP, Evers BJ, et al. Tissue-engineered rotator cuff tendon using porcine small intestine submucosa. Histology and mechanical evaluation in dogs. Am J Sports Med 2001;29:175184.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 11.

    Stoll MR, Cook JL, Pope ER, et al. The use of porcine small intestinal submucosa as a biomaterial for perineal herniorrhaphy in the dog. Vet Surg 2002;31:379390.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 12.

    Aiken SW, Badylak SF, Toombs JP, et al. Small intestinal submucosa as an intra-articular ligamentous graft material: a pilot study in dogs. Vet Comp Orthop Traumatol 1994;7:124128.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 13.

    Dahlgren LA, van der Meulen MC, Bertram JE, et al. Insulin-like growth factor-1 improves cellular and molecular aspects of healing in a collagenase-induced model of flexor tendonitis. J Orthop Res 2002;20:910919.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14.

    Fortier LA, Mohammed HO, Lust G, et al. Insulin-like growth factor-1 enhances cell-based repair of articular cartilage. J Bone Joint Surg Br 2002;84:276288.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 15.

    Crow BD, Haltom JD, Carson WL, et al. Evaluation of a novel biomaterial for intrasubstance muscle laceration repair. J Orthop Res 2007;25:396403.

  • 16.

    Beatty MW, Ojha AK, Cook JL, et al. Small intestinal submucosa versus salt-extracted polyglycolic acid-poly-L-lactic acid: a comparison of neocartilage formed in two scaffold materials. Tissue Eng 2002;8:955968.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 17.

    Pei M, Solchaga LA, Seidel J, et al. Bioreactors mediate the effectiveness of tissue engineering scaffolds. FASEB J 2002;16:16911694.

  • 18.

    Voytik-Harbin SL, Brightman AO, Kraine MR, et al. Identification of extractable growth factors from small intestinal submucosa. J Cell Biochem 1997;67:478491.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 19.

    Dalla Vecchia L, Engum S, Kogon B, et al. Evaluation of small intestine submucosa and acellular dermis as diaphragmatic prostheses. J Pediatr Surg 1999;34:167171.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 20.

    Fox DB, Cook JL, Kuroki K, et al. Effects of dynamic compressive load on collagen-based scaffolds seeded with fibroblast-like synoviocytes. Tissue Eng 2006;12:15271537.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 21.

    Derwin KA, Baker AR, Spragg RK, et al. Commercial extracellular matrix scaffolds for rotator cuff tendon repair. Biomechanical, biochemical, and cellular properties. J Bone Joint Surg Am 2006;88:26652672.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 22.

    Badylak S, Arnoczky SP, Plouhar P, et al. Naturally occurring extracellular matrix as a scaffold for musculoskeletal repair. Clin Orthop Relat Res 1999;367 (suppl):S333S343.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 23.

    Zheng MH, Chen J, Kirilak Y, et al. Porcine small intestine submucosa is not an acellular collagenous matrix and contains porcine DNA: possible implications in human application. J Biomed Mater Res B Appl Biomater 2005;73:6167.

    • Search Google Scholar
    • Export Citation
  • 24.

    McPherson TB, Badylak SF. Characterization of fibronectin derived from porcine small intestinal submucosa. Tissue Eng 1998;4:7583.

  • 25.

    Hodde JP, Hiles MC. Bioactive FGF-2 in sterilized extracellular matrix. Wounds 2001;13:195201.

  • 26.

    McDevitt CA, Widey GM, Cutrone RM. Transforming growth factor-B1 in a sterilized tissue derived from the pig small intestine submucosa. J Biomed Mater Res 2003;67A:637640.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 27.

    Hodde JP, Record RD, Liang HA, et al. Vascular endothelial growth factor in porcine-derived extracellular matrix. Endothelium 2001;8:1124.

  • 28.

    Hurst RE, Bonner RB. Mapping of the distribution of significant proteins and proteoglycans in small intestinal submucosa by fluorescence microscopy. J Biomater Sci Polym Ed 2001;12:12671279.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 29.

    Hodde JP, Record RD, Tullius RS, et al. Retention of endothelial cell adherence to porcine-derived extracellular matrix after disinfection and sterilization. Tissue Eng 2002;8:225234.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 30.

    Iannotti JP, Codsi MJ, Kwon YW, et al. Porcine small intestine submucosa augmentation of surgical repair of chronic two-tendon rotator cuff tears. A randomized controlled trial. J Bone Joint Surg Am 2006;88:12381244.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 31.

    Harding ML. Human meniscal chondrocyte culture and matrix infiltration with specific reference to meniscal generation. Knee 2003;10:4345.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 32.

    Kimuli M, Eardley I, Southgate J. In vitro assessments of decellularized porcine dermis as a matrix for urinary tract reconstruction. BJU Int 2004;94:859866.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 33.

    Boon ME, Ruijgrok JM, Vardaxis MJ. Collagen implants remain supple not allowing fibroblast ingrowth. Biomaterials 1995;16:10891093.

  • 34.

    Belcher HJ, Zic R. Adverse effect of porcine collagen interposition after trapeziectomy: a comparative study. J Hand Surg [Br] 2001;26:159164.

  • 35.

    Beniker D, McQuillan D, Livesey S, et al. The use of acellular dermal matrix as a scaffold for periosteum replacement. Orthopedics 2003;26:s591s596.

    • Search Google Scholar
    • Export Citation
  • 36.

    Marinucci L, Lilli C, Guerra M, et al. Biocompatibility of collagen membranes crosslinked with glutaraldehyde or diphenylphosphoryl azide: an in vitro study. J Biomed Mater Res A 2003;67:504509.

    • Search Google Scholar
    • Export Citation
  • 37.

    Nimni ME, Cheung D, Strates B, et al. Chemically modified collagen; a natural biomaterial for tissue replacement. J Biomed Mater Res 1987;21:741771.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 38.

    Ramires PA, Milella E. Biocompatibility of poly(vinyl alcohol)-hyaluronic acid and poly(vinyl alcohol)-gellan membranes crosslinked by glutaraldehyde vapors. J Mater Sci Mater Med 2002;13:119123.

    • Crossref
    • Search Google Scholar
    • Export Citation

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