Cell-seeded polyurethane-fibrin structures – A possible system for intervertebral disc regeneration.docx

C Mauth et al.Intevertebral disc regenerationCEuropeanMauth etCcisal. and Materials Vol. 18 2009 (pages27-39)CELL-SEEDED POLYURETHANE-FIBRIN STRUCTURES - A POSSIBLE SYSTEMFOR INTERVERTEBRAL DISC REGENERATIONC. Mauth , E. Bono , S. Haas , G. Paesold , H. Wiese , G. Maier , N. Boos and U. Graf-Hausner *1§1§12332I1 School of Life Sciences and Facility Management, Institute of Chemistry and Biological Chemistry, CampusRcidbach, Einsicdlcrstrassc 31, CH-8820 Wacdcnswil/Zurich, Switzerland2 University Hospital Balgrist, Department of Orthopedics, Forchstrasse 340, CH-8008 Zurich, Switzerland3 polyMaterials AG, Innovapark 20, D-87600 Kaufbeuren, Germany§ Both authors contributed equallyAbstractIntroduction29Nowadays, intervertebral disc (IVD) degeneration is oneof the principal causes of low back pain involving highexpense within the health care system. The long-term goalis the development of a medical treatment modality focusedon a more biological regeneration of the inner nucleuspulposus (NP). Hence, interest in the endoscopicimplantation of an injectable material took center stage inthe recent past. We report on the development of a novelpolyurethane (PU) scaffold as a mechanically stable carriersystem fbr the reimplantation of expanded autologous IVD-derived cells (disc cells) to stimulate regenerative processesand restore the chondrocyte-like tissue within the NP.Intcrrcrtcbral disc (IVD) degeneration is an agc-rclatcdprocess affecting the biomechanical properties of the spineand is assumed to be one of the principal causes of lowerback pain. During disc degeneration, dehydration of thenucleus pulposus (NP), due to loss of proteoglycans anddisorganization of the extracellular matrix causes aninefficient transfer of load between the vertebral bodiesleading to further degeneration or even to damage of theannulus fibross (AF) (disc herniation) (Urban andRoberts, 2003).Current treatments arc highly invasive surgicalprocedures such as spinal fusion and discectomy. ThePrimary human disc cells were seeded into newly developed clinical solution is either complete disc removal inPU spheroids which were subsequently encapsulated infibrin hydrogel. The study aims to analyze adhesionproperties, proliferation capacity and phenotypiccharacterization of these cells. Polymerase chain reactionconjunction with spinal interbody fusion or total discarthroplasty (Mayer, 2005). Both approaches are notbiological nor do they preserve the natural disc function,and revision surgery is frequently necessary. In contrast,was carried out to detect the expression of genes specifically biological approaches aim at the stimulation of discfibrin.expressed by native IVD cells. Biochemical analysesshowed an increased DNA content, and a progressiveenhancement of total collagen and glycosaminoglycans(GG) was observed during cell culturc.Thc results suggestthe synthesis of an appropriate extracellular matrix as wellas a stable mRNA expression of chondrogenic and/or NPspecific markers. In conclusion, the data presented indicatean alternative medical approach to current treatment optionsof degenerated IVD tissue.Keywords: intervertebral disc, polyurethane,scaffold, nucleus pulposus, cell encapsulation.* Address fbr conrspondcncc:Ursula Grai-HausnerCampus Reidbacl Einsiedlerstrasse 31CH-8820 Waedenswil/SwitzerlandTelephone Number: +41 58 934 55 18FAX Number: +41 58 934 5659E-mail: ursula.grafzhaw.chregeneration (Paesold et al. 2007) to avoid or at leastdelay surgical procedures.A potential alternative could be a tissue engineeringapproach to regenerate the inner NP tissue at an carly-stage of the degeneration process. The fbcus should beon biocompatible materials that allow three-dimensional(3D) cell culture and provide initial mechanical stabilityafter implantation. Thus, cells are given time to synthesizethe extracellular matrix required to resist the compressiveloads caused by daily movements. Moreover, the cellularscaffold has to promote cell adhesion and integration, andneeds to allow appropriate transport of nutrients and wasteproducts through the structure. For clinical application itis crucial that the material can be implanted by minimallyinvasive surgery, while cells maintain their viability andare homogenously distributed.Different synthetic biomaterials have been studied togenerate in vitro tissue constructs fbr subsequent discaugmentation, and are at different levels of preclinicaland clinical investigations (Di Martino et al., 2005).Studies have been performed using macroporous scaffoldssuch as collagen, hyaluronan, calcium phosphates,polylactide (Yang et al., 2005; Revell et al. 2007; Seguinet al.y 2004; Brown et al； 2005) as well as hydrogels likefibrin, gelatin, or chitosan (Yang et al. 2005; Bertram etal., 2005; Roughley