Engineering Pulmonary Valve Tissue Sheets from Human Umbilical Cord Perivascular Cells and Electrospun Polyurethane
Bibliographic record
Abstract
Objective: Bioengineered pulmonary valve (PV) tissue synthesized from mesenchymal stromal cells (MSCs) on a degradable biomaterial can overcome the limitations of non-viable structures through living valves with the potential to grow and remodel. An underused autologous cell source for heart valve tissue engineering (HVTE) are human umbilical cord perivascular cells (hUCPVCs), which are readily isolated at birth and have excellent regenerative capacity. Degradable, non-cytotoxic electrospun polyurethane (PU) scaffolds are a favourable biomaterial as fibre alignment can be varied to confer the mechanical anisotropy seen in the native leaflet. Furthermore, these scaffolds support fibroblast attachment and biodegrade without producing any cytotoxic by-products. Methods: To assess the in vitro performance of hUCPVCs, we examined their growth kinetics, differentiation, and ECM producing capacity under clinically advantageous xeno-free and chemically-defined (XF-CD) conditions. hUCPVC-PU compatibility was evaluated by assessing cell attachment, morphology and viability under XF-CD conditions. Results: hUCPVCs proliferated more rapidly (p<0.05) and retained a larger population of self-renewing colony forming unit-fibroblasts (p<0.05) than conventionally used bone marrow-derived MSCs (bm-MSCs) in XF-CD conditions. Further, hUCPVCs synthesized more collagen (p<0.05) and sulphated glycoasminoglycans (p<0.05) than bm-MSCs. Supplementation with 50 μM ascorbic acid increased collagen (p<0.05) while depressing elastin (p<0.05) synthesis by bm-MSCs, but did not affect ECM deposition by hUCPVCs. After induction with osteogenic or adipogenic media, bm-MSCs differentiated accordingly, while hUCPVCs retained their initial phenotype. hUCPVCs demonstrated excellent attachment (97 ± 11%) to PU scaffolds. Further, pre-coating scaffolds with fibronectin promoted spreading and alignment of hUCPVCs. After 1 week in culture, calcein AM/ethidium homodimer staining revealed complete coverage of the scaffolds by viable hUCPVCs. Conclusions: hUCPVCs cultured on electrospun PU offer a promising platform for in vitro engineering of PV leaflet tissue. On-going studies are assessing tissue synthesis and functionality to further evaluate the potential of this novel combination of hUCPVCs and anisotropic PU scaffolds. KEYWORD: ICTEHV-O-19 The authors do not declare any conflict of interest.
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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 | 0.000 |
| 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 | 0.000 | 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".