Regeneration of Intervertebral Disc Tissue by Resorbable Cell-Free Polyglycolic Acid-Based Implants in a Rabbit Model of Disc Degeneration

Abbushi, Alexander; Endres, Michaela; Čabraja, Mario; Kroppenstedt, Stefan; Thomale, Ulrich W.; Sittinger, Michael; Hegewald, Aldemar Andrés; Morawietz, Lars; Aj, Lemke; Bansemer, Victor-Götz; Kaps, Christian; Woiciechowsky, Christian

doi:10.1097/brs.0b013e3181788760

Cited by 78 publications

(53 citation statements)

References 24 publications

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“…The chemotactic ability of BMP-13 could help in the recruitment of host NP cells into tissue engineered scaffolds for the proper integration in to the implant. 28 However, with the knowledge that stem cells may also exist within the disc, [29][30][31] further analysis to determine whether the migratory cells we observed 8 were actual NP cells or were stem cells residing within the NP tissue needs to be delineated. It is also interesting to note a recent finding that BMP-13 can induce the differentiation of stem cells to a nucleus pulposus phenotype.…”

Section: Bmp-13 In Human Intervertebral Discmentioning

confidence: 99%

Localization of bone morphogenetic protein 13 in human intervertebral disc and its molecular and functional effects in vitro in 3D culture

Gulati

Chung

Wei

et al. 2015

Journal Orthopaedic Research

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Our laboratory has demonstrated that bone morphogenetic protein 13 prevented the effects of annular injury in an ovine model, maintaining intervertebral disc height, cell numbers and increasing extracellular matrix production compared to degenerated controls. The present study sought to examine the molecular effects of bone morphogenetic protein 13 on human degenerated disc cells and localize its expression in both human degenerate and scoliotic disc tissue. Effect of bone morphogenetic protein 13 on human derived nucleus pulposus, annulus fibrosus and endplate cells cultured in alginate beads was evaluated by changes in proteoglycan and collagen content. Migratory potential of disc cells towards bone morphogenetic protein 13 was also examined. Bone morphogenetic protein 13 induced significant proteoglycan accumulation in nucleus (18%), annulus (21%) and endplate (23%) cells cultured in alginate beads (p < 0.05) compared to controls. Further bone morphogenetic protein 13 increased collagen I and II protein expression in nucleus and endplate cells. Nucleus cells displayed a significant chemotactic response towards bone morphogenetic protein 13. The endogenous expression of bone morphogenetic protein 13 in degenerate disc tissue was not different to scoliotic disc. Bone morphogenetic protein 13 has the potential to enhance extracellular matrix accumulation and induce cell migration in certain disc cells. Keywords: bone morphogenetic protein 13; human intervertebral disc; low back pain; cell migration; intervertebral disc degeneration Chronic low back pain is strongly associated with intervertebral disc (IVD) degeneration. IVD consists of a central gelatinous nucleus pulposus (NP), surrounded circumferentially by annulus fibrosus (AF) and separated from the vertebral bodies by cartilaginous endplates (EPs). During IVD degeneration, cellular viability is decreased and the gel-like composition of NP becomes fibrous. Additionally, there is increasing irregularity and bifurcation of the lamellar structure of AF. 1Biological therapies aim to retard IVD degeneration and re-establish its biological function by restoring cellular viability and extracellular matrix (ECM). Growth factors such as bone morphogenetic proteins (BMPs), members of transforming growth factor beta (TGF-b) superfamily, play a critical role in stimulation of ECM formation and maintenance of cell numbers. The effect of BMPs on degenerate IVDs in vitro and in vivo has been extensively studied, 2 however, the role of BMP-13 in disc regeneration has not been explored. BMP-13, the human homologue of murine growth and differentiation factor 6, 3 has been highly associated with the stimulation of ECM production. BMP-13 induced aggrecan gene expression and proteoglycan (PG) synthesis in mouse mesenchymal cell line 4 and human articular chondrocytes.5 BMP-13 also stimulated gene expression of collagen II in mouse mesenchymal cell line 4 and collagen synthesis in juvenile bovine articular cartilage explants. 6 Moreover, Zhang et al.have demonstrated t...

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Section: Bmp-13 In Human Intervertebral Discmentioning

confidence: 99%

Localization of bone morphogenetic protein 13 in human intervertebral disc and its molecular and functional effects in vitro in 3D culture

Gulati

Chung

Wei

et al. 2015

Journal Orthopaedic Research

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“…Such a scaffold, combined with chemotactic agents, should allow the in situ recruitment of progenitor and disc cells. 13 In this concept, discomfort for patient and clinician is minimized, because the harvesting and culturing of cells prior to the surgical procedure are not necessary. Patients suffering from herniated discs could be treated in a one-step surgical procedure, in which a discectomy is combined with a functional replacement.…”

mentioning

confidence: 99%

“…Patients suffering from herniated discs could be treated in a one-step surgical procedure, in which a discectomy is combined with a functional replacement. 13 Acellular collagen constructs require additional sterilization steps prior to this stage. Because gamma sterilization has been described to have serious effects on collagen matrices, 14 its effect on rheology and swelling capacity of the current dense collagen scaffolds is also assessed.…”

mentioning

confidence: 99%

Rheological characterization of the nucleus pulposus and dense collagen scaffolds intended for functional replacement

Bron

Koenderink

Everts

et al. 2008

Journal Orthopaedic Research

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Lumbar discectomy is an effective therapy for neurological decompression in patients suffering from sciatica due to a herniated nucleus pulposus (NP). However, high numbers of patients suffering from persisting postoperative low back pain have resulted in many strategies targeting the regeneration of the NP. For successful regeneration, the stiffness of scaffolds is increasingly recognized as a potent mechanical cue for the differentiation and biosynthetic response of (stem) cells. The aim of the current study is to characterize the viscoelastic properties of the NP and to develop dense collagen scaffolds with similar properties. The scaffolds consisted of highly dense (0.5%-12%) type I collagen matrices, prepared by plastic compression. The complex modulus of the NP was 22 kPa (at 10 rad s À1 ), which should agree with a scaffold with a collagen concentration of 23%. The loss tangent, indicative of energy dissipation, is higher for the NP (0.28) than for the scaffolds (0.12) and was not dependent of the collagen density. Gamma sterilization of the scaffolds increased the shear moduli but also resulted in more brittle behavior and a reduced swelling capacity. In conclusion, by tuning the collagen density, we can approach the stiffness of the NP. Therefore, dense collagen is a promising candidate for tissue engineering of the NP that deserves further study, such as the addition of other proteins. ß

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“…These mechanisms seem to be more pronounced in heavily loaded discs of large adult animal models offering higher human like body weights. Smaller and younger animals achieve better results in regenerative disc therapies due to biomechanical, anatomical, and cellular differences offering higher regenerative potential [1,10,[12][13][14][15]. However, portability to the human situation seems to be more doubtful in small animal models and therapeutic strategies should finally be evaluated on large models with biomechanical properties similar to humans.…”

Section: Discussionmentioning

confidence: 99%

“…Cell-free implants made of polyglycolic acid (PGA) and HA induced the regeneration of articular cartilage in a sheep model [12]. In a rabbit model of disc degeneration, a cell-free PGA/HA nucleus implant facilitated the formation of nucleus pulposus repair tissue and limited the loss of disc height [13]. In a recent rabbit study of disc degeneration, cell-free PGA hyaluronan implants accelerated the healing process and were able to induce disc regeneration with cell migration into the defect [14].…”

Section: Introductionmentioning

confidence: 99%

Injection of a polymerized hyaluronic acid/collagen hydrogel matrix in an in vivo porcine disc degeneration model

et al. 2012

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Introduction Disc degeneration and re-herniation after nucleotomy procedures are common problems. Simultaneous application of hyaluronic acid (HA)-based matrix has been proposed to limit disc degeneration. This, however, is hampered by loss of the substituted matrix out of the disc. Hence, in situ polymerization of the injected matrix with ultraviolet light (UVL) directly used after injection may be useful. Therefore, this study evaluates a new HA/collagen hydrogel matrix with in situ polymerization after implantation in an established porcine nucleotomy model. Materials and methods 12 mature minipigs were used. A total of 60 lumbar discs were analyzed. 36 discs underwent partial nucleotomy with a 16G biopsy needle. Of those, 24 discs received matrix (porcine nucleus pulposus collagenous scaffold component and chemically modified HA) which was in situ polymerized using UVL immediately after transplantation. 12 nucleotomized discs and 24 non-nucleotomized discs served as controls. After 24 weeks, animals were killed. X-rays, MRIs, histology, and gene expression analysis were done. Results Disc height was reduced equally after sole nucleotomy and nucleotomy with HA treatment and in MRIs signal intensity decreased. For both nucleotomy groups, the nucleus histo-degeneration score showed a significant increase compared to controls. In histology, HA treatment resulted in more scarring and inflammation in the annulus. Gene expression of catabolic MMPs was up-regulated, whereas IFN-gamma, IL-6, and IL-1b were unchanged. Conclusion Although nucleotomy and administration of the implant material did not cause generalized inflammation of the disc, localized annular damage with annulus inflammation and scarring resulted in detrimental degenerative disc changes. As a result, therapeutic strategies should strongly focus on the prevention of annular damage or techniques for annular repair to remain disc integrity.

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Regeneration of Intervertebral Disc Tissue by Resorbable Cell-Free Polyglycolic Acid-Based Implants in a Rabbit Model of Disc Degeneration

Abstract: : The implantation of a cell-free PGA-hyaluronic acid implant immersed in serum after discectomy induces regeneration, resulting in improvement of the disc water content and preservation of the disc height 6 months after surgery.

Cited by 78 publications

References 24 publications

Localization of bone morphogenetic protein 13 in human intervertebral disc and its molecular and functional effects in vitro in 3D culture

Localization of bone morphogenetic protein 13 in human intervertebral disc and its molecular and functional effects in vitro in 3D culture

Rheological characterization of the nucleus pulposus and dense collagen scaffolds intended for functional replacement

Injection of a polymerized hyaluronic acid/collagen hydrogel matrix in an in vivo porcine disc degeneration model

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