Fibrin matrix provides a suitable scaffold for bone marrow stromal cells transplanted into injured spinal cord: A novel material for CNS tissue engineering

Abstract

Recent basic experiments have strongly suggested that cell transplantation therapy may promote functional recovery in patients with spinal cord injury (SCI). However, a safe and efficient transplantation technique still remains undetermined. This study, therefore, was aimed to clarify whether fibrin matrix could be a useful scaffold in bone marrow stromal cell (BMSC) transplantation for the injured spinal cord. To clarify the issue, three-dimensional structure of fibrin matrix was assessed and the green fluorescent protein (GFP)-expressing BMSC were cultured in fibrin matrix. The rats were subjected to spinal cord hemisection at T8 level, and the vehicle, BMSC or BMSC-fibrin matrix construct was implanted into the cavity. Neurologic function was serially evaluated. Using immunohistochemistry, we evaluated the survival, migration and differentiation of the transplanted cells at 4 weeks after transplantation. In the initial in vitro study, the BMSC could survive in fibrin matrix for 2 weeks. The animals treated with the BMSC-fibrin matrix construct showed significantly more pronounced recovery of neurologic function than vehicle- or BMSC-treated animals. Fibrin scaffold markedly improved the survival and migration of the transplanted cells. There was no significant difference in the percentage of cells doubly positive for GFP and microtubule-associated protein 2 between the animals treated with BMSC-fibrin matrix construct and those treated with BMSC, but a certain subpopulation of GFP-positive cells morphologically simulated the neurons in the animals treated with BMSC-fibrin matrix construct. These findings strongly suggest that fibrin matrix may be one of the promising candidates for a potential, minimally invasive scaffold for injured spinal cord, and that such strategy of tissue engineering could be a hopeful option in regeneration therapy for patients with SCI.

Osteogenic efficiency of in situ gelling poloxamine systems with and without bone morphogenetic protein-2

“…Alternative materials such as gelatin/-tricalcium phosphate (Yang et al, 2005), poly(L-lactic acid) (PLA) , poly(L-lactic-co-glycolic acid) (PLGA) (Jeon et al, 2007;Shen et al, 2009), hyaluronic acid (Kim and Valentini, 2002), fi brin gel (Itosaka et al, 2009) or porous hydroxyapatite composites (Sopyana et al, 2007) are under study. The recent developments in the research of BMP delivery carriers have been comprehensively revised by Bessa et al (2008a,b).…”

The Use of Chitosan-Based Scaffolds to Enhance Regeneration in the Nervous System

“…Interestingly, a couple of studies showed that chitooligosaccharides (COSs), the biodegradation products of chitosan, promote peripheral nerve regeneration and functional recovery in the rat sciatic nerve crush injury model and rabbit common peroneal nerve crush injury model, suggesting their potential application in peripheral nerve repair as neuroprotective agents (Gong et al, 2009;Jiang et al, 2009). Moreover, immunophilin FK506 combined with biodegradable chitosan guide provides neurotrophic and neuroprotective actions, promoting nerve regeneration in a rat sciatic nerve defect model .…”

“…A photocrosslinkable hydrogel based on chitosan has been in vitro successfully characterized and proposed as a new adhesive for peripheral nerve anastomosis (Rickett et al, 2011). Chitosan has further been used in combination with other biomaterials for bridging peripheral nerve gaps (Fan et al, 2008;Jiao et al, 2009;Lin et al, 2008;Simoes et al, 2010;Xie et al, 2005;Xie et al, 2008;Xu et al, 2009). Chitosan-polylactid acid (PLA) composite nerve conduits showed good biocompatibility and permeability, good mechanical strength, intensity, and elasticity, facilitating microsuture manipulation, and they provide enough mechanical strength to support nerve regeneration.…”

“…Yet, tubular grafts made out of chitosan membranes have been successfully used to improve peripheral nerve functional recovery after neurotmesis of the rat sciatic nerve, and they induced better nerve regeneration and functional recovery when compared with poly-lactic-polyglycolic acid (PLGA) control tubes (Simoes et al, 2010). A dual component artificial nerve conduit consisting of an outer chitosan microporous conduit and an internal oriented PGA filament matrix has been used to bridge a 10-mm defect in rats after long-term delay (3 or 6 months), resulting in reinnervation of the atrophic denervated muscle by regenerating neurites through new muscle-nerve connections (Jiao et al, 2009). The same conduit has been used to regenerate 30-mm beagle dog sciatic nerve defects, resulting in reconstruction and restoration of nerve continuity and functional recovery as indicated by improved locomotion activities of the operated limb after target muscle reinnervation .…”

“…Thus, the use of chitosan as a "fusogen" might be more advantageous as a potential clinical tool relative to nonionic polymers (e.g., PEG or P188). Due to its high biodegradability and biocompatibility,togetherwithitsspecific interactions with components of the extracellular matrix (ECM) and growth factors, chitosan employment is growing in a variety of applications, including implantable and injectable orthopedic and periodontal lsystems,drug delivery systems, woundhealing agents, lung surfactant additives, and tissue engineering scaffolds for tissue regeneration of skin, bone, and cartilage (Drury & Mooney, 2003;Gan & Wang, 2007;Janes, Fresneau, Marazuela, Fabra, & Alonso, 2001;Madihally & Matthew, 1999;Roy, Mao, Huang, & Leong, 1999;Suh & Matthew, 2000;Ueno et al, 1999;Yuan, Zhang, Yang,Wang,&Gu,2004;Zuoetal.,2006). Yet,chitosanisaversatilematerial currentlyusedinclinicalwounddressings,primarilyforitshemostaticproperty (Gustafson, Fulkerson, Bildfell, Aguilera, & Hazzard, 2007).…”