Nanofibrous biologic laminates replicate the form and function of the annulus fibrosus

Abstract

Successful engineering of load-bearing tissues requires recapitulation of their complex mechanical functions. Given the intimate relationship between function and form, biomimetic materials that replicate anatomic form are of great interest for tissue engineering applications. However, for complex tissues such as the annulus fibrosus, scaffolds have failed to capture their multi-scale structural hierarchy. Consequently, engineered tissues have yet to reach functional equivalence with their native counterparts. Here we present a novel strategy for annulus fibrosus tissue engineering that replicates this hierarchy with anisotropic nanofibrous laminates seeded with mesenchymal stem cells. These scaffolds directed the deposition of organized, collagen-rich extracellular matrix that mimicked the angle-ply, multi-lamellar architecture and achieved mechanical parity with native tissue after 10 weeks of in vitro culture. Further, we identified a novel role for inter-lamellar shearing in reinforcing the tensile response of biologic laminates, a mechanism that has not previously been considered for these tissues.

Bioactive electrospun scaffold for annulus fibrosus repair and regeneration

“…Furthermore, Gruber et al [16] showed that culture of human AFCs on electrospun polyamide nanofibers is permissive for secretion and assembly ECM components. Recently, a new study of Nerurkar et al [17] described a nanofibrous laminate that replicated the micro-architecture and tensile properties of AF. Furthermore, those authors showed the role of inter-lamellar ECM in reinforcing the tensile response of biologic laminates.…”

“…AF tissue engineering approaches have evaluated AF cells seeded in several types of 3D hydrogels or scaffolds [7,[14][15][16][17][18]. These studies have demonstrated that AF cells proliferate in 3D culture and synthesize ECM, reconstituting the histological structure of native tissue.…”

Hydrogel-Based Platforms for the Regeneration of Osteochondral Tissue and Intervertebral Disc

“…In particular, annulus and nucleus cells were seeded in scaffolds consisting of a crosslinked type I collagen/hyaluronan and the influence of different combinations of growth factors was studied [124]. Following this approach, nucleus and annulus cells have been cultured on a substrate of natural and synthetic polymers, obtaining interesting results [119,[123][124][125][126][127][128][129][130][131][132].…”

Intervertebral Disc Regeneration

“…The three main components of IVD aimed at tissue regeneration are: 1) AF (Sato et al, 2003;Chang et al, 2007;Helen and Gough, 2007;Nerurkar et al, 2007;Shao and Hunter, 2007;Wan et al, 2007;Nerurkar et al, 2008;Wang et al, 2008;Nerurkar et al, 2009); 2) NP (Baer et al, 2001;Sakai et al, 2003;Seguin et al, 2004;Bertram et al, 2005;Wilke et al, 2006;Roughley et al, 2006;Cloyd et al, 2007;Chou et al, 2008;Halloran et al, 2008;Richardson et al, 2008;Vernengo et al, 2008;Bron et al, 2009;Chou et al, 2009;Sawamura et al, 2009;Calderon et al, 2010;Silva-Correia et al, 2010a;Silva-Correia et al, 2010b;Reza and Nicoll, 2010;); and 3) both NP and AF by means of using biphasic scaffolds (Mizuno et al, 2004;Hamilton et al, 2005;Mizuno et al, 2006;Nerurkar et al, 2008;Nesti et al, 2008). It has been proposed that for producing a tissue resembling natural IVD, total IVD replacement could be required.…”

“…Besides, it should be mentioned that the mechanical properties of such implants should resemble those of the native AF (Setton et al, 2007;Bron et al, 2009). This explains in part why strategies for AF regeneration are mainly focused on synthetic materials and their processing onto porous scaffolds and electrospun nets (Sato et al, 2003;Wan et al, 2007;Helen and Gough, 2007;Nerurkar et al, 2007;Nerurkar et al, 2008aNerurkar et al, , 2008bNerurkar et al, 2009;Chang et al, 2007;Wan et al, 2008).…”