Recellularization of auricular cartilage via elastase-generated channels

Decellularized tissue matrices are promising substrates for tissue generation by stem cells to replace poorly regenerating tissues such as cartilage. However, the dense matrix of decellularized cartilage impedes colonisation by stem cells. Here, we show that digestion of elastin fibre bundles traversing auricular cartilage creates channels through which cells can migrate into the matrix. Human chondrocytes and bone marrow-derived mesenchymal stromal cells efficiently colonise elastin-treated scaffolds through these channels, restoring a glycosaminoglycan-rich matrix and improving mechanical properties while maintaining size and shape of the restored tissue. The scaffolds are also rapidly colonised by endogenous cartilage-forming cells in a subcutaneously implanted osteochondral biopsy model. Creating channels for cells in tissue matrices may be a broadly applicable strategy for recellularization and restoration of tissue function.

• Publication year

  2019

• Venue

  Biofabrication

• Publication date

  2019-04-26

• Fields of study

  Materials Science, Chemistry, Physics, Engineering, Medicine

• Identifiers
  DOI 10.1088/1758-5090/ab1436PMID 30921774
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• Transforming growth factor β induces bone marrow mesenchymal stem cell migration via noncanonical signals and N‐cadherin

  2018cited by this paper
• Isolating Pediatric Mesenchymal Stem Cells with Enhanced Expansion and Differentiation Capabilities

  2018cited by this paper
• Decellularization of porcine articular cartilage explants and their subsequent repopulation with human chondroprogenitor cells.

  2016cited by this paper
• Tissue composition regulates distinct viscoelastic responses in auricular and articular cartilage.

  2016cited by this paper
• Effects of Chondroitinase ABC-Mediated Proteoglycan Digestion on Decellularization and Recellularization of Articular Cartilage

  2016cited by this paper
• Silencing of Antichondrogenic MicroRNA‐221 in Human Mesenchymal Stem Cells Promotes Cartilage Repair In Vivo

  2016cited by this paper
• Cartilage extracellular matrix as a biomaterial for cartilage regeneration

  2016cited by this paper
• Nasal chondrocyte-based engineered autologous cartilage tissue for repair of articular cartilage defects: an observational first-in-human trial.

  2016cited by this paper
• The Challenge in Using Mesenchymal Stromal Cells for Recellularization of Decellularized Cartilage

  2016cited by this paper
• Microsphere-based scaffolds encapsulating chondroitin sulfate or decellularized cartilage

  2016cited by this paper
• Systematic Comparison of Protocols for the Preparation of Human Articular Cartilage for Use as Scaffold Material in Cartilage Tissue Engineering

  2016cited by this paper
• Guidelines for an optimized indentation protocol for measurement of cartilage stiffness: The effects of spatial variation and indentation parameters.

  2016influential reference
• Chondroinduction from Naturally Derived Cartilage Matrix: A Comparison Between Devitalized and Decellularized Cartilage Encapsulated in Hydrogel Pastes

  2016cited by this paper
• Differential Effects of Small Molecule WNT Agonists on the Multilineage Differentiation Capacity of Human Mesenchymal Stem Cells

  2016cited by this paper
• Biomechanical signals guiding stem cell cartilage engineering: from molecular adaption to tissue functionality.

  2016cited by this paper
• Isolation of phenotypically and functionally distinct endogeneous human bone marrow-derived mesenchymal stem/stromal cell subsets

  2016cited by this paper
• Matrix-Associated Autologous Chondrocyte Implantation

  2016cited by this paper
• Crosslinkable Hydrogels Derived from Cartilage, Meniscus, and Tendon Tissue

  2015cited by this paper
• Long-Term Expansion, Enhanced Chondrogenic Potential, and Suppression of Endochondral Ossification of Adult Human MSCs via WNT Signaling Modulation

  2015cited by this paper
• Xenograft bioprosthetic heart valves: Past, present and future.

  2015cited by this paper
• Decellularized Cartilage May Be a Chondroinductive Material for Osteochondral Tissue Engineering

  2015cited by this paper
• Mechanical regulation of mesenchymal stem cell differentiation

  2015cited by this paper
• Correction for Makris et al., Developing functional musculoskeletal tissues through hypoxia and lysyl oxidase-induced collagen cross-linking

  2015cited by this paper
• Conditions for seeding and promoting neo-auricular cartilage formation in a fibrous collagen scaffold.

  2015cited by this paper
• Characterization of bone marrow-derived mesenchymal stem cells in aging.

  2015cited by this paper
• Pro-Chondrogenic Effect of miR-221 and Slug Depletion in Human MSCs

  2014cited by this paper
• Chondrogenic differentiation of human bone marrow-derived mesenchymal stem cells in a simulated osteochondral environment is hydrogel dependent.

  2014cited by this paper
• Developing functional musculoskeletal tissues through hypoxia and lysyl oxidase-induced collagen cross-linking

  2014cited by this paper
• Electrospun cartilage-derived matrix scaffolds for cartilage tissue engineering.

  2014cited by this paper
• Incorporation of Aggrecan in Interpenetrating Network Hydrogels to Improve Cellular Performance for Cartilage Tissue Engineering

  2013cited by this paper
• TGF-β mediates homing of bone marrow-derived human mesenchymal stem cells to glioma stem cells.

  2013cited by this paper
• Induction of Re-Differentiation of Passaged Rat Chondrocytes Using a Naturally Obtained Extracellular Matrix Microenvironment

  2013cited by this paper
• Biomechanics of cartilage

  2013cited by this paper
• Decellularized Tracheal Matrix Scaffold for Tracheal Tissue Engineering: In Vivo Host Response

  2013cited by this paper
• Extracellular matrix scaffolds for cartilage and bone regeneration.

  2013cited by this paper
• NIH Image to ImageJ: 25 years of image analysis

  2012cited by this paper
• A review of the treatment methods for cartilage defects

  2012cited by this paper
• Decellularized Cartilage Matrix as a Novel Biomatrix for Cartilage Tissue-Engineering Applications

  2012cited by this paper
• An Osteochondral Culture Model to Study Mechanisms Involved in Articular Cartilage Repair

  2011cited by this paper
• Differences in Cartilage-Forming Capacity of Expanded Human Chondrocytes from Ear and Nose and Their Gene Expression Profiles

  2011cited by this paper
• Engineering Ear Constructs with a Composite Scaffold to Maintain Dimensions

  2011cited by this paper
• Hypoxia inhibits senescence and maintains mesenchymal stem cell properties through down-regulation of E2A-p21 by HIF-TWIST.

  2011cited by this paper
• A sandwich model for engineering cartilage with acellular cartilage sheets and chondrocytes.

  2011cited by this paper
• Articular cartilage repair and the evolving role of regenerative medicine

  2010cited by this paper
• Autologous Bone Marrow–Derived Mesenchymal Stem Cells Versus Autologous Chondrocyte Implantation

  2010cited by this paper
• Mapping Thickness of Nasal Septal Cartilage

  2010cited by this paper
• Chondrogenesis of Adult Stem Cells from Adipose Tissue and Bone Marrow: Induction by Growth Factors and Cartilage-Derived Matrix

  2009cited by this paper
• Novel 3D biomaterials for tissue engineering based on collagen and macroporous ceramics

  2009cited by this paper
• The Basic Science of Articular Cartilage

  2009cited by this paper
• Generating Ears from Cultured Autologous Auricular Chondrocytes by Using Two-Stage Implantation in Treatment of Microtia

  2009cited by this paper
• Chondrogenic Differentiation of Adipose-Derived Adult Stem Cells by a Porous Scaffold Derived from Native Articular Cartilage Extracellular Matrix

  2008cited by this paper
• Chemotaxis of human articular chondrocytes and mesenchymal stem cells

  2008cited by this paper
• Cartilaginous ECM component-modification of the micro-bead culture system for chondrogenic differentiation of mesenchymal stem cells.

  2007cited by this paper
• The In Vitro Migration Capacity of Human Bone Marrow Mesenchymal Stem Cells: Comparison of Chemokine and Growth Factor Chemotactic Activities

  2007cited by this paper
• A low temperature method of isolating normal human articular chondrocytes.

  2006cited by this paper
• Mechanobiological conditioning of stem cells for cartilage tissue engineering

  2006cited by this paper
• Possibility of selection of chondrogenic progenitor cells by telomere length in FGF‐2‐expanded mesenchymal stromal cells

  2006cited by this paper
• Synthetic biomaterials as instructive extracellular microenvironments for morphogenesis in tissue engineering

  2005cited by this paper
• The chondrocyte.

  2003cited by this paper
• Wnt proteins are lipid-modified and can act as stem cell growth factors

  2003cited by this paper
• A compositional analysis of human nasal septal cartilage.

  2003cited by this paper
• BMP‐2 and BMP‐9 promotes chondrogenic differentiation of human multipotential mesenchymal cells and overcomes the inhibitory effect of IL‐1

  2001cited by this paper
• Articular Cartilage Chondrocytes in Type I and Type II Collagen-GAG Matrices Exhibit Contractile Behavior in Vitro

  2000cited by this paper
• Thickness of human articular cartilage in joints of the lower limb

  1999cited by this paper
• Chondrogenic Differentiation of Cultured Human Mesenchymal Stem Cells from Marrow

  1998cited by this paper
• In vitro chondrogenesis of bone marrow-derived mesenchymal progenitor cells.

  1998cited by this paper
• Effect of transforming growth factor-β on proteoglycan synthesis by chondrocytes in relation to differentiation stage and the presence of pericellular matrix

  1998cited by this paper
• Effect of transforming growth factor-beta on proteoglycan synthesis by chondrocytes in relation to differentiation stage and the presence of pericellular matrix.

  1998cited by this paper
• Porcine and bovine cartilage transplants in cynomolgus monkey: II. Changes in anti-Gal response during chronic rejection.

  1997cited by this paper
• Porcine and bovine cartilage transplants in cynomolgus monkey: I. A model for chronic xenograft rejection.

  1997cited by this paper
• The chondrocyte, architect of cartilage. Biomechanics, structure, function and molecular biology of cartilage matrix macromolecules

  1995cited by this paper
• The cell density of human articular and costal cartilage.

  1967cited by this paper

• Decellularized Meniscus (MEND) as a biomaterial that supports stem cell invasion and chondrogenesis

  2025cites this paper
• Innovative tissue engineering strategies for auricular regeneration in microtia: Current advances and future perspectives

  2025cites this paper
• From Cartilage to Matrix: Protocols for the Decellularization of Porcine Auricular Cartilage

  2025cites this paper
• Comparative Analysis and Regeneration Strategies for Three Types of Cartilage

  2024cites this paper
• Identification of a Regenerative Protocol for Recellularizing Human Auricular Cartilage Scaffolds

  2024cites this paper
• A Pilot Study of Decellularized Cartilage for Laryngotracheal Reconstruction in a Neonatal Pig Model

  2023cites this paper
• Application of decellularization-recellularization technique in plastic and reconstructive surgery

  2023cites this paper
• Biomaterial-based scaffolds in promotion of cartilage regeneration: Recent advances and emerging applications

  2023cites this paper
• A Translational Tissue Engineering Approach to Airway Reconstruction Leveraging Decellularized Meniscus and Cartilage Progenitor Cells

  2022cites this paper
• Applications of Decellularized Materials for Tissue Repair

  2021cites this paper
• Advanced Multi-Dimensional Cellular Models as Emerging Reality to Reproduce In Vitro the Human Body Complexity

  2021cites this paper
• Nanofibrillar Decellularized Wharton's Jelly Matrix for Segmental Tracheal Repair

  2020cites this paper
• Reconstruction of Distal Nasal Defects Using Free Cartilage Batten Grafting With Secondary Intention Healing: A Retrospective Case Series of 129 Patients.

  2020cites this paper