Topical and local controlled release of stratifin for the improvement of hypertrophic scarring in open and surgically closed wounds
Bibliographic record
Abstract
Hypertrophic scar (HS), which results from the uncontrolled synthesis and excessive deposition of extracellular matrix (ECM) at sites of dermal injury, represents an undesirable endpoint of wound healing. Stratifin (SFN) was recently identified as a potent matrix methaloproteinase-1 (MMP-1) stimulatory factor in dermal fibroblasts. In this research project, it is hypothesized that stratifin can modulate the deposition of ECM components and prevent HS formation when it is applied topically to open wounds or locally delivered to surgically closed wounds. Four specific objectives were accomplished in this project. Under objective 1, a hydrogel /microsphere dermal implant was fabricated, specifically to be placed in surgical wounds before closure and locally deliver stratifin in a controlled manner to reduce HS formation. Microencapsulating stratifin complexed chitosan particles into PLGA microspheres allowed bioactive stratifin to be controllably released over 30 days with a reduced burst release. Under objective 2, use of a rat surgical wound model showed that the local controlled delivery of stratifin markedly reduced fibrosis and inflammation induced by drug-free implants, confirmed by a reduced collagen deposition, total tissue cellularity, and infiltrated CDHypertrophic scar (HS), which results from the uncontrolled synthesis and excessive deposition of extracellular matrix (ECM) at sites of dermal injury, represents an undesirable endpoint of wound healing. Stratifin (SFN) was recently identified as a potent matrix methaloproteinase-1 (MMP-1) stimulatory factor in dermal fibroblasts. In this research project, it is hypothesized that stratifin can modulate the deposition of ECM components and prevent HS formation when it is applied topically to open wounds or locally delivered to surgically closed wounds. Four specific objectives were accomplished in this project. Under objective 1, a hydrogel /microsphere dermal implant was fabricated, specifically to be placed in surgical wounds before closure and locally deliver stratifin in a controlled manner to reduce HS formation. Microencapsulating stratifin complexed chitosan particles into PLGA microspheres allowed bioactive stratifin to be controllably released over 30 days with a reduced burst release. Under objective 2, use of a rat surgical wound model showed that the local controlled delivery of stratifin markedly reduced fibrosis and inflammation induced by drug-free implants, confirmed by a reduced collagen deposition, total tissue cellularity, and infiltrated CD³⁺ immune cells. Under objective 3, the anti-fibrogenic effect of topically applied stratifin was investigated on open wounds created in a rabbit ear fibrotic model. Qualitative wound assessment showed a reduced HS in wounds treated with stratifin-impregnated CMC gel (0.002%, w/w) applied twice a day, confirmed with reduced scar volume including deposited collagen and total tissue cellularity. Under objective 4, CMC gel was modified into a thermoreversible emulgel, which demonstrated a significant effect on scar reduction through its occlusive effect. Using this emulgel and combining stratifin with acetylsalicylic acid significantly reduced HS, even with once a day application. In conclusion, the findings presented in this thesis provide further support for the importance and feasibility of using stratifin as an MMP-1 stimulatory factor for the improvement/prevention of dermal fibrosis in open and surgically closed wounds. These findings also provide additional information regarding controlled delivery of proteins to any kind of wounds, such as those resulting from surgical or burns. immune cells. Under objective 3, the anti-fibrogenic effect of topically applied stratifin was investigated on open wounds created in a rabbit ear fibrotic model. Qualitative wound assessment showed a reduced HS in wounds treated with stratifin-impregnated CMC gel (0.002%, w/w) applied twice a day, confirmed with reduced scar volume including deposited collagen and total tissue cellularity. Under objective 4, CMC gel was modified into a thermoreversible emulgel, which demonstrated a significant effect on scar reduction through its occlusive effect. Using this emulgel and combining stratifin with acetylsalicylic acid significantly reduced HS, even with once a day application. In conclusion, the findings presented in this thesis provide further support for the importance and feasibility of using stratifin as an MMP-1 stimulatory factor for the improvement/prevention of dermal fibrosis in open and surgically closed wounds. These findings also provide additional information regarding controlled delivery of proteins to any kind of wounds, such as those resulting from surgical or burns.
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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".