The Potential and Limitations of a Cell-Seeded Collagen/Hyaluronan Scaffold to Engineer an Intervertebral Disc-Like Matrix

Alini, Mauro; Li, Wei; Markovic, Paul; Aebi, Max; Spiro, Robert C.; Roughley, Peter J.

doi:10.1097/01.brs.0000048672.34459.31

Cited by 159 publications

(135 citation statements)

References 43 publications

Supporting

Mentioning

128

Contrasting

Unclassified

Order By: Relevance

“…Exciting advances in the field of tissue engineering have allowed spine researchers to begin developing novel therapeutic approaches in an attempt to intervene in and modulate the course of IVD degeneration by repairing, replacing or regenerating the herniated or degenerated NP [7][8][9][10]. However, these strategies are ineffective without a functional annulus fibrosus (AF) able to withstand the physiological intradiscal pressure.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Bioactive electrospun scaffold for annulus fibrosus repair and regeneration

et al. 2012

View full text Add to dashboard Cite

Purpose Annulus fibrosus (AF) tissue engineering is gathering increasing interest for the development of strategies to reduce recurrent disc herniation (DH) rate and to increase the effectiveness of intervertebral disc regeneration strategies. This study evaluates the use of a bioactive microfibrous poly(L-lactide) scaffold releasing Transforming Growth Factor (TGF)-b1 (PLLA/TGF) for the repair and regeneration of damaged AF. Methods The scaffold was synthesized by electrospinning, with a direct incorporation of TGF-b1 into the polymeric solution, and characterized in terms of morphology and drug release profile. Biological evaluation was performed with bovine AF cells (AFCs) that were cultured on the scaffold up to 3 weeks to quantitatively assess glycosaminoglycans and total collagen production, using bare electrospun PLLA as a control. Histological evaluation was performed to determine the thickness of the deposited neo-ECM. Results Results demonstrated that AFCs cultured on PLLA/TGF deposited a significantly greater amount of glycosaminoglycans and total collagen than the control, with higher neo-ECM thickness. Conclusions PLLA/TGF scaffold induced an anabolic stimulus on AFCs, mimicking the ECM three-dimensional environment of AF tissue. This bioactive scaffold showed encouraging results that allow envisaging an application for AF tissue engineering strategies and AF repair after discectomy for the prevention of recurrent DH.

show abstract

Section: Introductionmentioning

confidence: 99%

“…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.…”

Section: Introductionmentioning

confidence: 99%

Bioactive electrospun scaffold for annulus fibrosus repair and regeneration

et al. 2012

View full text Add to dashboard Cite

show abstract

“…To induce MSC chondrogenesis growth factors such as transforming growth factor (TGF)-b1, 2 or 3 [18], bone morphogenetic protein-2 [19], -4 [20], -7 [21] or -14 (GDF-5) [22], have been described to facilitate MSCs differentiation, however the aim of this project was to focus on the differences caused by variety of matrixes. In particular, many studies already described culture of MSCs embedded in several types of scaffolds, such as agarose gels [23], alginate beads [24][25][26], synthetic polymers [27,28] and other biomaterials [29][30][31][32]. These studies provide clear evidence that there is a need of a cell support for enhancing cell-cell and cell-matrix interactions and creating a 3D environment.…”

Section: Introductionmentioning

confidence: 99%

Influence of different commercial scaffolds on the in vitro differentiation of human mesenchymal stem cells to nucleus pulposus-like cells

et al. 2011

View full text Add to dashboard Cite

Introduction Cell-based therapies for regeneration of the degenerated intervertebral disc (IVD) are an alternative to current surgical intervention. Mesenchymal stem cells (MSCs), in combination with a scaffold, might be ideal candidates for regenerating nucleus pulposus (NP), the pressure-distributing part of the IVD. While the use of growth factors for MSCs differentiation currently receives major attention, in this study we compare the performance of sponge-like matrixes in supporting cell differentiation into NP-like cells. Materials and methods Four types matrixes approved as medical devices for other applications were tested as scaffolds for MSCs: two made of equine or porcine collagen, one of gelatin and one of chitosan. Bone marrowderived human MSCs were seeded in these scaffolds or embedded in alginate, as a three-dimensional control. After five weeks in culture, NP-like differentiation of the cellscaffold constructs was analyzed by qRT-PCR, histology, total DNA quantification, proteoglycan accumulation and immunohistochemistry. Results MSCs in collagen matrixes and gelatin produced more mRNA and proteins of the chondrogenic markers collagen type I, collagen type II (COL2) and aggrecan (ACAN), when compared with cells embedded in alginate or chitosan. Proteoglycan accumulation and cell survival were also higher in collagen and gelatin matrixes. Gene expression results were also confirmed by histological and immunohistochemical staining. In contrast to alginate control, the gene expression of the undesired bone marker osteopontin was lower in all tested groups. In porcine collagen supports, MSC expression ratio between COL2/ ACAN closely resembled the expression of nucleus pulposus cells, but gene expression of recently described NP markers keratin19, PAX1 and FOXF1 was lower. Conclusions Collagen supports provide a readily available, medically approved and effective scaffold for chondrogenic differentiation in vitro, but the phenotype of differentiated MSCs is not yet completely equivalent to that of NP cells.

show abstract

“…He could show that cells were viable and that they were able to proliferate after implantation. Alini et al [1], used Collagen-I/Hyaluronan scaffolds to culture nucleus/annulus cells. He showed that the cells proliferate but more proteoglycan was released into the culture medium and did not stay in the implant.…”

Section: Introductionmentioning

confidence: 99%

Is a collagen scaffold for a tissue engineered nucleus replacement capable of restoring disc height and stability in an animal model?

et al. 2006

View full text Add to dashboard Cite

The idea of a tissue engineered nucleus implant is to seed cells in a three-dimensional collagen matrix. This matrix may serve as a scaffold for a tissue engineered nucleus implant. The aim of this study was to investigate whether implantation of the collagen matrix into a spinal segment after nucleotomy is able to restore disc height and flexibility. The implant basically consists of condensed collagen type-I matrix. For clinical use, this matrix will be used for reinforcing and supporting the culturing of nucleus cells. In experiments, matrixes were concentrated with barium sulfate for X-ray purposes and cell seeding was disclaimed in order to evaluate the biomechanical performance of the collagen material. Six bovine lumbar functional spinal units, aging between 5 and 6 months, were used for the biomechanical in-vitro test. In each specimen, an oblique incision was performed, the nucleus was removed and replaced by a collagen-type-I matrix. Specimens were mounted in a custom-built spine tester, and subsequently exposed to pure moments of 7.5 Nm to move within the three anatomical planes. Each tested stage (intact, nucleotomy and implanted) was evaluated for range of motion, neutral zone and change in disc height. Removal of the nucleus significantly reduced disc height by 0.84 mm in respect to the intact stage and caused an instability in the segment. Through the implantation of the tissue engineered nucleus it was possible to restore this height and stability loss, and even to increase slightly the disc height of 0.07 mm compared with the intact stage. There was no statistical difference between the stability provided by the implant and intact stage. Results of movements in lateral bending and axial rotation showed the same trend compared to flexion/extension. However, implant extrusions have been observed in three of six cases during the flexibility assessment. The results of this study directly reflect the efficacy of vital nucleus replacement to restore disc height and to provide stability to intervertebral discs. However, from a biomechanical point of view, the challenge is to employ an appropriate annulus fibrosus sealing method, which is capable to keep the nucleus implant in place over a long-time period. Securing the nucleus implant inside the disc is one of the most important biomechanical prerequisites if such a tissue engineered implant shall have a chance for clinical application.

show abstract

The Potential and Limitations of a Cell-Seeded Collagen/Hyaluronan Scaffold to Engineer an Intervertebral Disc-Like Matrix

Cited by 159 publications

References 43 publications

Bioactive electrospun scaffold for annulus fibrosus repair and regeneration

Bioactive electrospun scaffold for annulus fibrosus repair and regeneration

Influence of different commercial scaffolds on the in vitro differentiation of human mesenchymal stem cells to nucleus pulposus-like cells

Is a collagen scaffold for a tissue engineered nucleus replacement capable of restoring disc height and stability in an animal model?

Contact Info

Product

Resources

About