Regeneration Intervertebral Disc Tissue: Resorbable Cell-Free Polyglycolic Acid

[Slackwater]

The below is an "orthobiologic solution" for lack of a better term. The good news is MRI signal intensity increased, disk heigh, regeneration.

The below is short of a (adipose) stem cell solution, however, positive results.


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PMID: 18520635

Spine. 2008 May 23. [Epub ahead of print]

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

Abbushi A, Endres M, Cabraja M, Kroppenstedt SN, Thomale UW, Sittinger M, Hegewald AA, Morawietz L, Lemke AJ, Bansemer VG, Kaps C, Woiciechowsky C.

From the
*Department of Neurosurgery, Charité, Campus Virchow-Klinikum, University Medicine of Berlin Germany;
†Department of Rheumatology, Tissue Engineering Laboratory, Charité, Campus Mitte, University Medicine of Berlin, Germany;
‡Department of Neurosurgery, Ruprecht-Karls-University Heidelberg, Germany;
§Institute for Pathology, Charité, Campus Mitte; and
¶Department of Radiology, Charité, Campus Virchow-Klinikum, University Medicine of Berlin, Germany.

STUDY DESIGN:
Different biologic strategies exist to treat degenerative disc disease. Tissue engineering approaches favor autologous chondrocyte transplantation. In our one-step-approach, a resorbable cell-free polyglycolic acid (PGA)-based implant is immersed in serum from whole blood and implanted into the disc defect directly after discectomy.

OBJECTIVES:
The aim of our study was to investigate the capacity of a cell-free implant composed of a PGA felt, hyaluronic acid, and serum to recruit disc cells and stimulate repair tissue formation in vivo after microdiscectomy in a rabbit model.

SUMMARY OF THE BACKGROUND DATA:
Disc tissue has a limited ability to regenerate after the degeneration process was once initiated. Therefore, we developed a cell-free resorbable implant that is able to attract local cells into the defect and induce proper repair tissue formation.

METHODS:
The cell-free implant consisting of PGA and hyaluronic acid was immersed in allogenic serum and implanted into the disc defect after discectomy in New Zealand white rabbits. One week and 6 months after the operation, the disc height index and the T2-weighted signal intensity index were determined using plane radiographs and magnetic resonance imaging. Finally, discs were explanted and investigated histologically. Animals with discectomy only served as controls.

RESULTS:
In our animal studies, we could demonstrate that the T2-weighted signal intensity of the operated discs decreased in both groups 1 week after surgery. However, after 6 months, the T2-weighted signal intensity index increased by 45% in the implanted group whereas the index decreased further by 11% in the sham group.

This corresponded to changes in the disc height index. Furthermore, the histologic examinations indicated cell migration into the defect and showed tissue regeneration.


CONCLUSION:
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.

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Slackwater
mva: 2-level lumbar surgical candidate

[Harrison]

Interesting on so many levels (pun not intended; admittedly overused). The disc height mention is fascinating -- but will it translate to bipedals?!

Thanks for posting this. Maybe progress is being made after all!

[Slackwater]

Originally posted by Harrison:
Interesting on so many levels (pun not intended; admittedly overused). The disc height mention is fascinating -- but will it translate to bipedals?!

Thanks for posting this. Maybe progress is being made after all!

The progress is iterative in a positive direction. The above is a ways from human use (bipedal); it is not an alternative in the next two (2) to x years in the U.S, therefore ADR TDR, Fusion, microdiscectomy, microsequestrectomy, ...

Resorbable Cell-Free Polyglycolic Acid-Based Implants could act as a carrier, rather than using and adeno-associated virus for growth factors (OP-1 / rhBMP-7, TGF-B1, blah blah), or it might be in conjunction w/adipose stem cells, or ADCT, or ... I believe in general the rabbit tests with biologics translate to humans.

Hyaluronic acid is mentioned in the medical literature (and other research material) as a carrier for cartilage repair in the knee and spine. Can't remember by report by collagen type I or type II w/o lookup, ...


Slackwater
mva: 2-level lumbar surgical candidate

[Justin]

Hyaluronic acid is mentioned in the medical literature (and other research material) as a carrier for cartilage repair in the knee and spine. Can't remember by report by collagen type I or type II w/o lookup,

It's collagen type II.

Great work Slack!
Justin

[Slackwater]

PMID: 18520635

Spine. 2008 May 23. [Epub ahead of print]

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

Abbushi A, Endres M, Cabraja M, Kroppenstedt SN, Thomale UW, Sittinger M, Hegewald AA, Morawietz L, Lemke AJ, Bansemer VG, Kaps C, Woiciechowsky C.

From the
*Department of Neurosurgery, Charité, Campus Virchow-Klinikum, University Medicine of Berlin Germany;
†Department of Rheumatology, Tissue Engineering Laboratory, Charité, Campus Mitte, University Medicine of Berlin, Germany;
‡Department of Neurosurgery, Ruprecht-Karls-University Heidelberg, Germany;
§Institute for Pathology, Charité, Campus Mitte; and
¶Department of Radiology, Charité, Campus Virchow-Klinikum, University Medicine of Berlin, Germany.

Key Points

◙ Polyglycolic acid based implants regenerate intervertebral discs.

◙ Using a rabbit disc degeneration model, we show that cell-free polyglycolic acid based implants form disc repair tissue after nucleotomy.

◙ The proof of principle in vivo shows maintenance of disc height after implanting the polyglycolicacid based construct.


References my look up items

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5. Ganey T, Libera J, Moos V, et al. Disc chondrocyte transplantation in a canine model: a treatment for degenerated or damaged intervertebral disc. Spine 2003;28:2609–20.

6. Sakai D, Mochida J, Yamamoto Y, et al. Transplantation of mesenchymal stem cells embedded in Atelocollagen gel to the intervertebral disc: a potential therapeutic model for disc degeneration. Biomaterials 2003;24:3531–41.

8. Meisel HJ, Ganey T, Hutton WC, et al. Clinical experience in cell-based therapeutics: intervention and outcome. Eur Spine J 2006;15 (Suppl 15): 397–405.

10. Behrens P, Bitter T, Kurz B, et al. Matrix-associated autologous chondrocyte transplantation/implantation (MACT/MACI)–5-year follow-up. Knee 2006; 13:194–202.

11. Hollander AP, Dickinson SC, Sims TJ, et al. Maturation of tissue engineered cartilage implanted in injured and osteoarthritic human knees. Tissue Eng 2006;12:1787–98.

12. Ossendorf C, Kaps C, Kreuz PC, et al. Treatment of posttraumatic and focal osteoarthritic cartilage defects of the knee with autologous polymer-based three-dimensional chondrocyte grafts: 2-year clinical results. Arthritis Res Ther 2007;9:R41.

14. Wilke HJ, Heuer F, Neidlinger-Wilke C, et al. Is a collagen scaffold for a tissue engineered nucleus replacement capable of restoring disc height and stability in an animal model? Eur Spine J 2006;15 (Suppl 3):S433–S438.

19. Nagae M, Ikeda T, Mikami Y, et al. Intervertebral disc regeneration using platelet-rich plasma and biodegradable gelatin hydrogel microspheres. Tissue Eng 2007;13:147–58.

20. Pfirrmann CW, Metzdorf A, Zanetti M, et al. Magnetic resonance classification of lumbar intervertebral disc degeneration. Spine 2001;26:1873–8.

21. Sakai D, Mochida J, Iwashina T, et al. Regenerative effects of transplanting mesenchymal stem cells embedded in atelocollagen to the degenerated intervertebral disc. Biomaterials 2006;27:335–45.