Elsevier

Biomaterials

Volume 28, Issue 25, September 2007, Pages 3587-3593
Biomaterials

Leading Opinion
The extracellular matrix as a biologic scaffold material

https://doi.org/10.1016/j.biomaterials.2007.04.043Get rights and content

Abstract

Biologic scaffolds composed of naturally occurring extracellular matrix (ECM) have received significant attention for their potential therapeutic applications. The full potential of the ability of ECM scaffolds to promote constructive remodeling will not be realized, however, until an understanding of the biology and the external influences that affect biology, are better achieved. The factors that appear important for the constructive remodeling of ECM biologic scaffolds are its ability to be rapidly and completely degraded with the generation of downstream bioactive molecules, the bioinductive properties of the functional molecules that compose native ECM material and the ability to engineer its mechanical properties at the time of implantation through an understanding of its collagen fiber microstructure.

Section snippets

The extracellular matrix as a biologic scaffold material

The extracellular matrix (ECM) is by definition nature's ideal biologic scaffold material. The ECM is custom designed and manufactured by the resident cells of each tissue and organ and is in a state of dynamic equilibrium with its surrounding microenvironment [1]. The structural and functional molecules of the ECM provide the means by which adjacent cells communicate with each other and with the external environment [2], [3], [4]. The ECM is obviously biocompatible since host cells produce

The bioinductive properties of ECM bioscaffolds

The mechanisms by which scaffolds composed of naturally occurring ECM facilitate the constructive remodeling of tissues are not completely understood. It is clear, however, that the bioinductive properties of these scaffolds play a very important role in tissue remodeling. The viscoelastic behavior, biomechanical properties, and ability to support host cell attachment through collagen, fibronectin and laminin ligands are insufficient alone to explain the constructive remodeling events that are

Biomechanical properties of ECM

The mechanical properties of the ECM are largely a consequence of its collagen fiber architecture and kinematics. With the exception of ECM derived from the small intestine (SIS) and urinary bladder, there has been almost no systematic examination of the biomechanical properties of ECM scaffold materials, especially with respect to the effect of processing methods (e.g., sterilization) upon such properties.

SIS has been shown to have a global preferred fiber alignment along the longitudinal axis

Host tissue response to xenogeneic SIS–ECM

The use of xenogeneic ECM as a biologic scaffold should logically raise questions regarding the host (recipient) immune response. Many ECM scaffolds are of porcine origin including SIS. However, bovine tissue (e.g., TissueMend®) and allogeneic human tissue (e.g., AlloDerm) are well represented among the group of ECM biomaterials. Non-autologous biologic materials have been used for many years in humans without evidence of adverse immunologic outcomes. For example, porcine heart valves for valve

Degradation of SIS–ECM

Perhaps the most important characteristic of SIS–ECM is its ability to be rapidly and completely degraded [20], [82], [83]. Quantitative studies of 14C-labeled SIS used in both augmentation cytoplasty procedures and Achilles tendon reconstruction show that greater than 50% of the ECM scaffold is degraded and removed from the implantation site by 28 days and virtually all of the SIS is replaced by 60 days. The fate of 95% of the SIS degradation products is urinary excretion and it appears that

Summary

Biologic scaffolds composed of naturally occurring ECM such as SIS have received significant attention for their potential therapeutic applications. The full potential of the ability of ECM scaffolds to promote constructive remodeling will not be realized, however, until an understanding of the biology and the external influences that affect biology, are better achieved. The factors that appear important for the constructive remodeling of SIS are its ability to be rapidly and completely

References (84)

  • S.F. Badylak et al.

    Small intestinal submucosa as a large diameter vascular graft in the dog

    J Surg Res

    (1989)
  • R. Misseri et al.

    Small intestinal submucosa bladder neck slings for incontinence associated with neuropathic bladder

    J Urol

    (2005)
  • A.M. Smith et al.

    Novel bile duct repair for bleeding biliary anastomotic varices: case report and literature review

    J Gastroint Surg

    (2005)
  • T.M. MacLeod et al.

    Evaluation of a porcine origin acellular dermal matrix and small intestinal submucosa as dermal replacements in preventing secondary skin graft contraction

    Burns

    (2004)
  • M. Metcalf et al.

    Surgical technique for xenograft (SIS) augmentation of rotator-cuff repairs

    Oper Tech Orthop

    (2002)
  • S.G. Sclamberg et al.

    Six-month magnetic resonance imaging follow-up of large and massive rotator cuff repairs reinforced with porcine small intestinal submucosa

    J Shoulder Elbow Surg

    (2004)
  • F. Mantovani et al.

    Reconstructive urethroplasty using porcine acellular matrix

    Eur Urol

    (2003)
  • D. Schultheiss et al.

    Functional tissue engineering of autologous tunica albuginea: a possible graft for Peyronie's disease surgery

    Eur Urol

    (2004)
  • K.D. Sievert et al.

    Off-shelf commercially available acellular collagen matrix SIS® by Cook for urethral reconstruction. Abstract 958

    Eur Urol Suppl

    (2005)
  • A. Assmy et al.

    Use of single-layer small intestinal submucosa (SIS) for long-segment ureteral replacement: a pilot study. Abstract 333

    Eur Urol Suppl

    (2004)
  • A. El-Assmy et al.

    Use of single layer small intestinal submucosa for long segment ureteral replacement: a pilot study

    J Urol

    (2004)
  • B.K. Oelschlager et al.

    The use of small intestine submucosa in the repair of paraesophageal hernias: initial observations of a new technique

    Am J Surg

    (2003)
  • L.D. Knoll

    Use of porcine small intestinal submucosal graft in the surgical management of Peyronie's disease

    Urology

    (2001)
  • T. John et al.

    Porcine small intestinal submucosa is not an ideal graft materials for Peyronie's disease surgery

    Urology

    (2006)
  • M. Metcalf et al.

    Surgical technique for xenograft (SIS) augmentation of rotator-cuff repairs

    Oper Techn Orthop

    (2002)
  • J. Hodde et al.

    Fibronectin peptides mediate HMEC adhesion to porcine-derived extracellular matrix

    Biomaterials

    (2002)
  • S.F. Badylak et al.

    Marrow-deprived cells populate scaffolds composed of xenogeneic extracellular matrix

    Exp Hematol

    (2001)
  • M. Malmsten et al.

    Bacterial killing by heparin-binding peptides from PRELP and thrombospondin

    Matrix Biol

    (2006)
  • D.O. Freytes et al.

    Biaxial strength of multilaminated extracellular matrix scaffolds

    Biomaterials

    (2004)
  • R.H. Raeder et al.

    Natural anti-galactose alpha1,3 galactose antibodies delay, but do not prevent the acceptance of extracellular matrix xenografts

    Transplant Immunol

    (2002)
  • A. Mantovani et al.

    The chemokine system in diverse forms of macrophage activation and polarization

    Trends Immunol

    (2004)
  • A. Mantovani et al.

    Macrophage polarization comes of age

    Immunity

    (2005)
  • F.A. Rickey et al.

    Re-generation of tissue about an animal-based scaffold: AMS studies of the fate of the scaffold

    Nucl Instrum Meth Phy Res

    (2000)
  • M.L. Ritchey et al.

    Successful use of tunica vaginalis grafts for treatment of severe penile chordee in children

    J Urol

    (2003)
  • M.J. Bissell et al.

    Dynamic reciprocity: how do extracellular matrix and hormones direct gene expression?

    Prog Clin Biol Res

    (1987)
  • F. Rosso et al.

    From cell–ECM interactions to tissue engineering

    J Cell Physiol

    (2004)
  • Cell-to-cell contact and extracellular matrix editorial overview: cell–cell and cell–matrix interactions—running, jumping, standing still

    Curr Opin Cell Biol

    (2003)
  • S.E. Dahms et al.

    Composition and biomechanical properties of the bladder acellular matrix graft: comparative analysis in rat, pig and human

    Br J Urol

    (1998)
  • M. Huang et al.

    Uptake and cytotoxicity of chitosan molecules and nanoparticles: effects of molecular weight and degree of deacetylation

    Pharm Res

    (2004)
  • J.E. Valentin et al.

    Extracellular matrix bioscaffolds for orthopaedic applications: a comparative histologic study

    J Bone Joint Surg Am

    (2006)
  • G.A. Abraham et al.

    Evaluation of the porcine intestinal collagen layer as a biomaterial

    J Biomed Mater Res

    (2000)
  • S.A. Alpert et al.

    Bladder neck fistula after the complete primary repair of exstrophy: a multi-institutional experience

    J Urol

    (2005)
  • Cited by (0)

    Editor's Note: Leading Opinions: This paper is one of a newly instituted series of scientific articles that provide evidence-based scientific opinions on topical and important issues in biomaterials science. They have some features of an invited editorial but are based on scientific facts, and some features of a review paper, without attempting to be comprehensive. These papers have been commissioned by the Editor-in-Chief and reviewed for factual, scientific content by referees.

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