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- Title
Ex vivo testing of biomaterials for intervertebral disc repair using organ culture bioreactors.
- Authors
Grad, Sibylle
- Abstract
INTRODUCTION: The intervertebral disc (IVD) functions to distribute mechanical loads acting on the spine and to enable flexibility of the spine in multiple degrees of freedom. Degeneration of the IVD is a multifactorial condition that can lead to chronic low back pain and impaired mobility. Degeneration is characterized by a breakdown of the extracellular matrix (ECM) within the nucleus pulposus (NP) and the annulus fibrosus (AF) of the IVD. Natural and synthetic biomaterials hold great promise for IVD repair. Hydrogels are particularly suitable for the NP, which is a highly hydrated tissue, while fibrous scaffolds may be suitable for closure of the AF. Organ culture bioreactors are instrumental for preclinical testing of the biomaterials’ performance, bridging the gap between in vitro and in vivo studies. Here the requirements for NP and AF repair are discussed, and examples of bioreactor-controlled ex vivo studies are demonstrated. EXPERIMENTAL: IVDs used for organ culture are harvested from bovine tails that are obtained from the slaughterhouse. To induce breakdown and loss of the ECM, either enzymatic or mechanical damage is applied. For NP repair, a hydrogel is injected into the center of the IVD. For AF repair, suture, or adhesive material is required to avoid dislocation under mechanical load. The IVDs are then cultured and loaded in the bioreactor under physiological loading conditions (i.e. axial compression, 0.2 MPa, 0.2 Hz) for 2 h /day. Disc height changes, cell viability, ECM content, and gene expression are assessed after 1-4 weeks of culture. RESULTS AND DISCUSSION: For NP repair, the properties of the hydrogel were optimized to meet the mechanical requirements, while preserving the phenotype of embedded cells. We found that a hyaluronic acid-based interpenetrating network hydrogel was suitable as a cell carrier for NP repair. When implanted in an ex vivo IVD organ culture model, the hydrogel supported cell viability, phenotype expression of encapsulated NP cells and IVD matrix production over four weeks under physiological loading. In another, enzymatic IVD degeneration model, a synthetic NP repair hydrogel showed potential to retain the disc height and integrate into the native tissue after two weeks of culture in a bioreactor under physiological loading. For AF repair, a biomaterial strategy comprising of electrospun polycaprolactone scaffold and fibrin-genipin adhesive was optimized and tested in an AF delamination organ culture model. The repair material created a tight seal on the damage and restored the mechanical properties, while showing minimal cytotoxicity. This outcome was achieved after one week of culture under physiological uniaxial loading conditions, while the persistence under multiaxial loading will need to be confirmed. CONCLUSIONS: These examples show the suitability of IVD organ culture bioreactors to test the feasibility of a range of biomaterials for NP and AF repair. Depending on the research question, different models can be created, and different biological and biomechanical parameters can be evaluated. Ex vivo loaded organ culture models are in line with the 3Rs principles of in vivo testing.
- Subjects
ORGAN culture; CHRONIC pain; CELL culture; MECHANICAL loads; BIOMATERIALS; NUCLEUS pulposus; BIOREACTORS; INTERVERTEBRAL disk
- Publication
Chemical Industry / Hemijska Industrija, 2024, Vol 78, p6
- ISSN
0367-598X
- Publication type
Article