The influence of biomaterial properties on the phenotypic behavior of intervertebral disc cells in vitro and in vivo
Bibliographic record
Abstract
The intervertebral disc (IVD) is a fibro-cartilaginous tissue that functions to support and distribute loads and permit motion of the spine. The disc is a composite structure consisting of the lamellar annulus fibrosus comprised of organized collagen fibers arranged concentrically around the gelatinous, semi-fluid nucleus pulposus (NP). Intervertebral disc degeneration has become a significant health concern in the United States. A tissue-engineered intradiscal replacement of the NP represents a potential strategy for treatment of disc degeneration. However, engineering approaches to treat disc degeneration require an understanding of disc cell biology and knowledge of biomaterial properties that modulate IVD cell function. This thesis project explored the effects of two- and three-dimensional culture conditions on the phenotypic behavior of IVD cells in vitro and in vivo. It was determined through gene expression and immunohistochemical analyses that primary IVD cells from 5-8 population doublings expanded on two-dimensional, tissue culture polystyrene were not significantly different from freshly isolated cells, such that they could be used to study the phenotypic behavior of these cells in vitro. It was also shown that the three-dimensional culture environment, whether in a fibrous or hydrated gel format, has a greater effect on the cellular phenotype than the distinct origin of the cells within the tissue. Building on these basic science investigations, additional work focused on developing a biomaterial scaffold that recapitulated the native environment of the disc and allowed for functional tissue growth. A photo-crosslinkable alginate hydrogel was successfully synthesized and characterized for NP cell encapsulation. Nucleus pulposus cells encapsulated in photo-crosslinked alginate hydrogels not only exhibited characteristic type II collagen and proteoglycan gene expression and accumulation, but were able to assemble a mechanically functional matrix. Unconfined compression testing of cell-seeded photo-crosslinked hydrogels after 8 weeks in vivo revealed that constructs had reached an equilibrium Young's modulus of 4.31±1.39 kPa, which is comparable that of native NP tissue. Taken together, the outcomes of this project have provided a cell culture paradigm for investigating IVD tissue formation as well as a new biomaterial scaffold for functional IVD repair. Moving forward, we hope to continue evaluating photo-crosslinked alginate hydrogels to determine optimal culture parameters for development of a biological NP replacement.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.001 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".