Membrane Culture of Bone Marrow Stromal Cells Yields Better Tissue Than Pellet Culture for Engineering Cartilage-Bone Substitute Biphasic Constructs in a Two-Step Process
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Bibliographic record
Abstract
Our long-term goal is to treat osteochondral lesions with bioengineered biphasic constructs. We have previously demonstrated that biphasic constructs, created in vitro with primary chondrocytes harvested from healthy joints and a porous calcium polyphosphate (CPP) substrate bone substitute, could successfully repair a focal defect in sheep joints. However, primary chondrocytes are limited in supply and cannot be used in engineering constructs large enough for clinical use. Thus, we developed a robust protocol to predifferentiate sheep bone marrow-derived stromal cells to chondrocytes on collagen-coated polytetrafluoroethane membrane inserts, and harvest the chondrocytes that develop and subsequently culturing these predifferentiated cells scaffold-free on the intended articulation surface of the CPP. Chondrocytes predifferentiated on membrane culture accumulated similar matrix as those in conventional pellet culture, but expressed less Col1a1 RNA. Membrane culture predifferentiated cells gave rise to a functionally superior hyaline cartilage tissue compared to pellet culture predifferentiated cells. Studies demonstrated that 2 weeks of membrane predifferentiation culture followed by 8 weeks of biphasic construct culture was the optimal culture period at which the compressive mechanical strength and the accumulation of extracellular matrix were maximized while avoiding tissue mineralization. This protocol will be used to generate implants for preclinical study to determine their ability to repair osteochondral lesions.
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Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.000 | 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 it