Collagen-low molecular weight hyaluronic acid semi-interpenetrating network loaded with gelatin microspheres for cell and growth factor delivery for nucleus pulposus regeneration

Roman Tsaryk, Antonio Gloria, Teresa Russo, Laura Anspach, Roberto De Santis, Shahram Ghanaati, Ronald E. Unger, Luigi Ambrosio, C. James Kirkpatrick

Research output: Contribution to journalArticlepeer-review

Abstract

Intervertebral disc (IVD) degeneration is one of the main causes of low back pain. Current surgical treatments are complex and generally do not fully restore spine mobility. Development of injectable extracellular matrix-based hydrogels offers an opportunity for minimally invasive treatment of IVD degeneration. Here we analyze a specific formulation of collagen-low molecular weight hyaluronic acid (LMW HA) semi-interpenetrating network (semi-IPN) loaded with gelatin microspheres as a potential material for tissue engineering of the inner part of the IVD, the nucleus pulposus (NP). The material displayed a gel-like behavior, it was easily injectable as demonstrated by suitable tests and did not induce cytotoxicity or inflammation. Importantly, it supported the growth and chondrogenic differentiation potential of mesenchymal stem cells (MSC) and nasal chondrocytes (NC) in vitro and in vivo. These properties of the hydrogel were successfully combined with TGF-β3 delivery by gelatin microspheres, which promoted the chondrogenic phenotype. Altogether, collagen-LMW HA loaded with gelatin microspheres represents a good candidate material for NP tissue engineering as it combines important rheological, functional and biological features.

Original languageEnglish
Pages (from-to)10-21
Number of pages12
JournalActa Biomaterialia
Volume20
DOIs
StatePublished - 1 Jul 2015
Externally publishedYes

Bibliographical note

Funding Information:
The funding was provided by EU FP7 project Disc Regeneration (Grant No. NMP3-LA-2008-213904 ). The funding source had no role in the study design, collection, analysis and interpretation of data, writing of the report and in the decision to submit the article for publication. The authors would like to thank Susanne Barth, Ulrike Hilbig, Anne Sartoris, Mykhaylo Reshetnykov and Mike Barbeck for their excellent technical assistance. We are also grateful to Prof. Constantin Landes and Dr. Larissa Seidmann for tissue collection.

Publisher Copyright:
© 2015 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

Keywords

  • Chondrocyte
  • Collagen
  • Hydrogel
  • Intervertebral disc
  • Mesenchymal stem cell

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