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Fibrin Sealant Combined with Fibroblasts and PDGF Enhance wound Healing in Excisional Wounds
Author(s) -
Mogford J. E.,
Tawil B.,
Mustoe T. A.
Publication year - 2004
Publication title -
wound repair and regeneration
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.847
H-Index - 109
eISSN - 1524-475X
pISSN - 1067-1927
DOI - 10.1111/j.1067-1927.2004.0abstractaa.x
Subject(s) - granulation tissue , fibrin , wound healing , thrombin , fibrinogen , chemistry , fibroblast , medicine , pathology , surgery , immunology , platelet , in vitro , biochemistry
A number of strategies have been explored for the treatment of cutaneous defects such as protein growth factor or gene therapy approaches. Alternative approaches include dermal or dermal‐epidermal skin substitutes or clot substitutes such as fibrin sealants (FS’s). Here we test the fibrinogen‐thrombin formulation of fibrin sealant combined with fibroblasts and PDGF in wound healing models. Four formulations varying in fibrinogen and thrombin concentration were applied to full‐thickness biopsy wounds in the rabbit ear cutaneous wound‐healing model with or without cultured rabbit dermal fibroblasts (RDFs; 3 × 10 5 cells/wound) embedded in the fibrinogen component. At post‐wounding day 7, there was no difference in the diluted vs. non‐diluted formulations for either the promotion of granulation tissue coverage of the open wounds or total granulation tissue area when tested without embedded cells. Including the RDFs, the highest degree of wound coverage by granulation tissue was observed in the combined dilution formulation (17.3 mg/ml fibrinogen, 167 U/ml thrombin; n = 10) that was 167%(p < 0.05) of the non‐diluted FS containing cells (50 mg/ml fibrinogen, 250 U/ml thrombin; n = 10). Inclusion of fibroblasts increased granulation tissue area within the wounds vs. FS alone (p < 0.05) for each diluted formulation although no differences in this parameter was observed within each group (FS alone or with embedded cells). However, addition of the vulnerary growth factor PDGF‐B (3 μg; n = 4) with the embedded RDFs in the combined dilution formulation increased granulation tissue area over 2‐fold (p < 0.01). Additionally, the presence of the RDFs promoted incorporation of the granulation tissue with and epithelial migration over the FS suggesting an active interaction between cells delivered to the wound by FS and the host repair cells. The findings suggest the progress of cutaneous defect repair can be enhanced by ex vivo cell delivery in Fibrin Sealant that is adjusted to balance hemostasis with promotion of wound healing processes.