Nonwoven-based gelatin/polycaprolactone membrane proves suitability in a preclinical assessment for treatment of soft tissue defects.
Standard preclinical assessments in vitro often have limitations regarding their transferability to human beings, mainly evoked by their nonhuman and tissue-different/nontissue-specific source. Here, we aimed at employing tissue-authentic simple and complex interactive fibroblast-epithelial cell systems and their in vivo-relevant biomarkers for preclinical in vitro assessment of nonwoven-based gelatin/polycaprolactone membranes (NBMs) for treatment of soft tissue defects. NBMs were composed of electrospun gelatin and polycaprolactone nanofiber nonwovens. Scanning electron microscopy in conjunction with actin/focal contact integrin fluorescence revealed successful adhesion and proper morphogenesis of keratinocytes and fibroblasts, along with cells' derived extracellular matrix deposits. The "feel-good factor" of cells under study on the NBM was substantiated by forming a confluent connective tissue entity, which was concomitant with a stratified epithelial equivalent. Immunohistochemistry proved tissue authenticity over time by abundance of the biomarker vimentin in the connective tissue entity, and chronological increase of keratins KRT1/10 and involucrin expression in epithelial equivalents. Suitability of the novel NBM as wound dressing was evidenced by an almost completion of epithelial wound closure in a pilot mini-pig study, after a surgical intervention-caused gingival dehiscence. In summary, preclinical assessment by tissue-authentic cell systems and the animal pilot study revealed the NBM as an encouraging therapeutic medical device for prospective clinical applications.
1 Department of Oral Biotechnology, University Medical Center Freiburg , Freiburg, Germany .
Simon
S
Schulz
Marco
M
Angarano
Martin
M
Fabritius
Rolf
R
Mülhaupt
Michel
M
Dard
Marcel
M
Obrecht
Pascal
P
Tomakidi
Thorsten
T
Steinberg
D000818:Animals; D001458:Bandages; D002478:Cells, Cultured; D018920:Coculture Techniques; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D005780:Gelatin / Q000494:pharmacology*; D005881:Gingiva / Q000166:cytology; D006801:Humans; D007150:Immunohistochemistry; D015603:Keratinocytes / Q000166:cytology / Q000187:drug effects / Q000648:ultrastructure; D008567:Membranes, Artificial; D008856:Microscopy, Fluorescence; D010519:Periodontium / Q000166:cytology; D011091:Polyesters / Q000494:pharmacology*; D015203:Reproducibility of Results; D017695:Soft Tissue Injuries / Q000473:pathology* / Q000628:therapy*; D013552:Swine; D013556:Swine, Miniature; D014746:Vimentin / Q000378:metabolism; D014945:Wound Healing / Q000187:drug effects
D008567:Membranes, Artificial; D011091:Polyesters; D014746:Vimentin; C016240:polycaprolactone; D005780:Gelatin