Multiphasic, Multistructured and Hierarchical Strategies for Cartilage Regeneration.

Cartilage tissue is a complex nonlinear, viscoelastic, anisotropic, and multiphasic material with a very low coefficient of friction, which allows to withstand millions of cycles of joint loading over decades of wear. Upon damage, cartilage tissue has a low self-reparative capacity due to the lack of neural connections, vascularization, and a latent pool of stem/chondro-progenitor cells. Therefore, the healing of articular cartilage defects remains a significant clinical challenge, affecting millions of people worldwide. A plethora of biomaterials have been proposed to fabricate devices for cartilage regeneration, assuming a wide range of forms and structures, such as sponges, hydrogels, capsules, fibers, and microparticles. In common, the fabricated devices were designed taking in consideration that to fully achieve the regeneration of functional cartilage it is mandatory a well-orchestrated interplay of biomechanical properties, unique hierarchical structures, extracellular matrix (ECM), and bioactive factors. In fact, the main challenge in cartilage tissue engineering is to design an engineered device able to mimic the highly organized zonal architecture of articular cartilage, specifically its spatiomechanical properties and ECM composition, while inducing chondrogenesis, either by the proliferation of chondrocytes or by stimulating the chondrogenic differentiation of stem/chondro-progenitor cells. In this chapter we present the recent advances in the development of innovative and complex biomaterials that fulfill the required structural key elements for cartilage regeneration. In particular, multiphasic, multiscale, multilayered, and hierarchical strategies composed by single or multiple biomaterials combined in a well-defined structure will be addressed. Those strategies include biomimetic scaffolds mimicking the structure of articular cartilage or engineered scaffolds as models of research to fully understand the biological mechanisms that influence the regeneration of cartilage tissue.

[1]  Y. Kuo,et al.  Heparin-conjugated scaffolds with pore structure of inverted colloidal crystals for cartilage regeneration. , 2011, Colloids and surfaces. B, Biointerfaces.

[2]  N. Kawazoe,et al.  Collagen Scaffolds with Controlled Insulin Release and Controlled Pore Structure for Cartilage Tissue Engineering , 2014, BioMed research international.

[3]  Lorenzo Moroni,et al.  3D Fiber‐Deposited Electrospun Integrated Scaffolds Enhance Cartilage Tissue Formation , 2008 .

[4]  Stephen D. Thorpe,et al.  Modulating Gradients in Regulatory Signals within Mesenchymal Stem Cell Seeded Hydrogels: A Novel Strategy to Engineer Zonal Articular Cartilage , 2013, PloS one.

[5]  C. Wilhelm,et al.  Use of Magnetic Forces to Promote Stem Cell Aggregation During Differentiation, and Cartilage Tissue Modeling , 2013, Advanced materials.

[6]  Jason A Burdick,et al.  Engineering cartilage tissue. , 2008, Advanced drug delivery reviews.

[7]  Jun Zhang,et al.  Manufacture of layered collagen/chitosan-polycaprolactone scaffolds with biomimetic microarchitecture. , 2014, Colloids and surfaces. B, Biointerfaces.

[8]  Krishnendu Roy,et al.  Engineering articular cartilage with spatially-varying matrix composition and mechanical properties from a single stem cell population using a multi-layered hydrogel. , 2011, Biomaterials.

[9]  Antonios G Mikos,et al.  Fabrication and characterization of multiscale electrospun scaffolds for cartilage regeneration , 2013, Biomedical materials.

[10]  Guangdong Zhou,et al.  A novel method for the direct fabrication of growth factor-loaded microspheres within porous nondegradable hydrogels: controlled release for cartilage tissue engineering. , 2012, Journal of controlled release : official journal of the Controlled Release Society.

[11]  Naoki Kawazoe,et al.  Preparation of collagen porous scaffolds with a gradient pore size structure using ice particulates , 2013 .

[12]  M. Becker,et al.  Maximizing phenotype constraint and extracellular matrix production in primary human chondrocytes using arginine-glycine-aspartate concentration gradient hydrogels. , 2013, Acta biomaterialia.

[13]  P. R. Weeren,et al.  Comparative study of depth-dependent characteristics of equine and human osteochondral tissue from the medial and lateral femoral condyles. , 2012, Osteoarthritis and cartilage.

[14]  Aaron M. Scurto,et al.  Microsphere-based scaffolds for cartilage tissue engineering: using subcritical CO(2) as a sintering agent. , 2010, Acta biomaterialia.

[15]  B. Heng,et al.  Functional biomaterials for cartilage regeneration. , 2012, Journal of biomedical materials research. Part A.

[16]  Wim E Hennink,et al.  Covalent attachment of a three-dimensionally printed thermoplast to a gelatin hydrogel for mechanically enhanced cartilage constructs. , 2014, Acta biomaterialia.

[17]  Richard Tuli,et al.  Multilineage differentiation of human mesenchymal stem cells in a three-dimensional nanofibrous scaffold. , 2005, Biomaterials.

[18]  Koichi Masuda,et al.  Tensile mechanical properties of bovine articular cartilage: Variations with growth and relationships to collagen network components , 2003, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[19]  A. Bhosale,et al.  Articular cartilage: structure, injuries and review of management. , 2008, British medical bulletin.

[20]  Miya Ishihara,et al.  The properties of bioengineered chondrocyte sheets for cartilage regeneration , 2009, BMC biotechnology.

[21]  A. Gomoll,et al.  The quality of healing: Articular cartilage , 2014, Wound repair and regeneration : official publication of the Wound Healing Society [and] the European Tissue Repair Society.

[22]  Ching-Chuan Jiang,et al.  Repair of articular cartilage defects: review and perspectives. , 2009, Journal of the Formosan Medical Association = Taiwan yi zhi.

[23]  A. Mikos,et al.  Electrospun poly(epsilon-caprolactone) microfiber and multilayer nanofiber/microfiber scaffolds: characterization of scaffolds and measurement of cellular infiltration. , 2006, Biomacromolecules.

[24]  J. Burdick,et al.  The influence of degradation characteristics of hyaluronic acid hydrogels on in vitro neocartilage formation by mesenchymal stem cells. , 2009, Biomaterials.

[25]  Liming Bian,et al.  Enhanced MSC chondrogenesis following delivery of TGF-β3 from alginate microspheres within hyaluronic acid hydrogels in vitro and in vivo. , 2011, Biomaterials.

[26]  L. Chow,et al.  Peptide‐Directed Spatial Organization of Biomolecules in Dynamic Gradient Scaffolds , 2014, Advanced healthcare materials.

[27]  Xiabin Jing,et al.  Biodegradable synthetic polymers: Preparation, functionalization and biomedical application , 2012 .

[28]  Farshid Guilak,et al.  Composite Three‐Dimensional Woven Scaffolds with Interpenetrating Network Hydrogels to Create Functional Synthetic Articular Cartilage , 2013, Advanced functional materials.

[29]  T. Okano,et al.  A novel recovery system for cultured cells using plasma-treated polystyrene dishes grafted with poly(N-isopropylacrylamide). , 1993, Journal of biomedical materials research.

[30]  Silvia Panzavolta,et al.  Co-electrospun gelatin-poly(L-lactic acid) scaffolds: modulation of mechanical properties and chondrocyte response as a function of composition. , 2014, Materials science & engineering. C, Materials for biological applications.

[31]  A. Poole,et al.  Composition and structure of articular cartilage: a template for tissue repair. , 2001, Clinical orthopaedics and related research.

[32]  A Ratcliffe,et al.  Cartilage and diarthrodial joints as paradigms for hierarchical materials and structures. , 1992, Biomaterials.

[33]  A. Mikos,et al.  Review: tissue engineering for regeneration of articular cartilage. , 2000, Biomaterials.

[34]  Rui L. Reis,et al.  Nanostructured 3D Constructs Based on Chitosan and Chondroitin Sulphate Multilayers for Cartilage Tissue Engineering , 2013, PloS one.

[35]  R. Bank,et al.  Ageing and zonal variation in post-translational modification of collagen in normal human articular cartilage. The age-related increase in non-enzymatic glycation affects biomechanical properties of cartilage. , 1998, The Biochemical journal.

[36]  Robert L Sah,et al.  Tissue engineering of articular cartilage with biomimetic zones. , 2009, Tissue engineering. Part B, Reviews.

[37]  Gerard A Ateshian,et al.  Zonal chondrocytes seeded in a layered agarose hydrogel create engineered cartilage with depth-dependent cellular and mechanical inhomogeneity. , 2009, Tissue engineering. Part A.

[38]  Farshid Guilak,et al.  Chondrogenic differentiation of adipose-derived adult stem cells in agarose, alginate, and gelatin scaffolds. , 2004, Biomaterials.

[39]  M. Stevens,et al.  Combinatorial scaffold morphologies for zonal articular cartilage engineering , 2014, Acta biomaterialia.

[40]  Nathan J. Castro,et al.  Enhanced human bone marrow mesenchymal stem cell functions in novel 3D cartilage scaffolds with hydrogen treated multi-walled carbon nanotubes , 2013, Nanotechnology.

[41]  T. Okano,et al.  Temperature-responsive culture dishes allow nonenzymatic harvest of differentiated Madin-Darby canine kidney (MDCK) cell sheets. , 2000, Journal of biomedical materials research.

[42]  Masayuki Yamato,et al.  Articular Cartilage Regeneration Using Cell Sheet Technology , 2014, Anatomical record.