Biomimetic Fibrin–Hyaluronan Hydrogels for Nucleus Pulposus Regeneration

Abstract

Aim: To develop a biomimetic polymeric injectable hydrogel that can support nucleus pulposus (NP) regeneration. Materials & methods: Natural polymer-based hydrogels were synthesized using fibrinogen (FBG) and hyaluronic acid (HA), conjugated by a novel two-step procedure. Bovine NP cells were cultured in FBG–HA conjugate-based 3D beads in vitro and in a nucleotomized organ culture model. Results: FBG–HA conjugate-based hydrogels prepared with 235 KDa HA at a FBG/HA w/w ratio of 17:1 showed superior gel stability and mechanical properties and markedly increased glycosaminoglycan synthesis compared with a FBG/HA mixture-based hydrogels or fibrin gels. Gene-expression levels of NP markers were maintained in vitro. In organ culture, NP cells seeded in FBG–HA conjugate-based hydrogels showed better integration with native NP tissue compared with fibrin gels. Moreover, FBG–HA conjugate-based hydrogels restored compressive stiffness and disc height after nucleotomy under dynamic load. Conclusion: Specific FBG–HA conjugate-based hydrogels may be suitable as injectable materials for minimally invasive, biological NP regeneration.

Keywords::

• fibrinogen–hyaluronan conjugate
• hydrogel
• intervertebral disc
• nucleus pulposus
• regeneration

Acknowledgements

The authors thank N Goudsouzian and M Bluvol (AO Research Institute Davos) for support with histology, and thank D Eglin, M Glarner and M D’Este for support with rheology measurements.

Financial & competing interests disclosure

KM Kaplan, A Wertzel, B Amit and A Yayon are employees of Procore Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

KM Kaplan, A Wertzel, B Amit and A Yayon are employees of Procore Ltd. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.