Cell biology

Epidermal growth factor

Biology

Biomedical engineering

Growth factor

Materials science

Wound dressing

Receptor

Regeneration (biology)

Biochemistry

Biomaterial

Immunology

Basic fibroblast growth factor

Fibroblast growth factor

In vitro

Internal medicine

Skin repair

Composite material

Medicine

Chemistry

Keratinocyte growth factor

Fibroblast

Wound healing

Journal of Tissue Engineering and Regenerative Medicine

Journal of Tissue Engineering and Regenerative MedicineVolume 12, Issue 6 p. 1508-1518 RESEARCH ARTICLE The dual delivery of KGF and bFGF by collagen membrane to promote skin wound healing Yili Qu, Yili Qu State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, P. R. China Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, P. R. ChinaYili Qu and Cong Cao contribute equally to this workSearch for more papers by this authorCong Cao, Cong Cao orcid.org/0000-0002-5500-061X Center of Stomatology, China-Japan Friendship Hospital, Beijing, P. R. ChinaYili Qu and Cong Cao contribute equally to this workSearch for more papers by this authorQingqing Wu, Qingqing Wu Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University, Chongqing, P. R. ChinaSearch for more papers by this authorAi Huang, Ai Huang State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, P. R. ChinaSearch for more papers by this authorYing Song, Ying Song State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, P. R. ChinaSearch for more papers by this authorHongling Li, Hongling Li State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, P. R. ChinaSearch for more papers by this authorYi Zuo, Yi Zuo Research Center for Nano-Biomaterials, and Analytical and Testing Center, Sichuan University, Chengdu, P. R. ChinaSearch for more papers by this authorChenyu Chu, Chenyu Chu State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, P. R. ChinaSearch for more papers by this authorJidong Li, Jidong Li Research Center for Nano-Biomaterials, and Analytical and Testing Center, Sichuan University, Chengdu, P. R. ChinaSearch for more papers by this authorYi Man, Corresponding Author Yi Man manyi780203@126.com State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, P. R. China Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China Correspondence Yi Man, State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, P. R. China. Email: manyi780203@126.comSearch for more papers by this author Yili Qu, Yili Qu State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, P. R. China Department of Prosthodontics, West China Hospital of Stomatology, Sichuan University, Chengdu, P. R. ChinaYili Qu and Cong Cao contribute equally to this workSearch for more papers by this authorCong Cao, Cong Cao orcid.org/0000-0002-5500-061X Center of Stomatology, China-Japan Friendship Hospital, Beijing, P. R. ChinaYili Qu and Cong Cao contribute equally to this workSearch for more papers by this authorQingqing Wu, Qingqing Wu Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Stomatological Hospital of Chongqing Medical University, Chongqing, P. R. ChinaSearch for more papers by this authorAi Huang, Ai Huang State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, P. R. ChinaSearch for more papers by this authorYing Song, Ying Song State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, P. R. ChinaSearch for more papers by this authorHongling Li, Hongling Li State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, P. R. ChinaSearch for more papers by this authorYi Zuo, Yi Zuo Research Center for Nano-Biomaterials, and Analytical and Testing Center, Sichuan University, Chengdu, P. R. ChinaSearch for more papers by this authorChenyu Chu, Chenyu Chu State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, P. R. ChinaSearch for more papers by this authorJidong Li, Jidong Li Research Center for Nano-Biomaterials, and Analytical and Testing Center, Sichuan University, Chengdu, P. R. ChinaSearch for more papers by this authorYi Man, Corresponding Author Yi Man manyi780203@126.com State Key Laboratory of Oral Diseases, Sichuan University, Chengdu, P. R. China Department of Oral Implantology, West China Hospital of Stomatology, Sichuan University, Chengdu, P.R. China Correspondence Yi Man, State Key Laboratory of Oral Diseases, Sichuan University, Chengdu 610041, P. R. China. Email: manyi780203@126.comSearch for more papers by this author First published: 29 April 2018 https://doi.org/10.1002/term.2691Citations: 34 Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat Abstract The major challenges associated with skin regeneration can include hindered vascularization and an insufficient degree of epithelization. In view of the complexity of these processes and the control signals on which they depend, one possible solution to these limitations could be simulating normal skin development and wound repair via the exogenous delivery of multiple cytokines. Here, we report the use of keratinocyte growth factor (KGF or FGF-7) and basic fibroblast growth factor (bFGF or FGF-2) released chemically modified collagen membranes to facilitate skin wound healing. The results from in vitro studies confirmed that this system resulted in higher cellular proliferation and faster cell migration. After transplanting the biomaterial onto an excisional wound healing model, the dual growth factor group, compared with the single growth factor groups and empty control group, showed more highly developed vascular networks and organized epidermal regeneration in the wounds. As a consequence, this experimental group showed mature epidermal coverage. Overall, this novel approach of releasing growth factors from a collagen membrane opens new avenues for fulfilling unmet clinical needs for wound care. CONFLICT OF INTEREST The authors have declared that there is no conflict of interest. Citing Literature Supporting Information Filename Description term2691-sup-0001-supplementary_materials_revised.docxWord 2007 document , 4.3 MB Table S1: Physiological effects of bFGFs and KGFs during wound healing Figure S1. SEM analyses. (a) Surface morphology of collagen membrane. (b) Cross section view of collagen membrane. Highly disordered fibers and porous structure could be seen both from surface and cross section. Scale bar A = 20 μm, scale bar B = 10 μm. Figure S2. Cell proliferation of each group was examined at day 1, 3 and 5 using CCK-8 assay. (A) The presence of KGF showed an improvement on HaCaT cell proliferation and 10 ng/cm2 KGF revealed a further improvement. (B) bFGF could stimulate HSFs proliferation in a concentration-dependent manner. *Significant difference compared to control group (without growth factors), p < 0.05. **significant difference between any groups, p < 0.05. (C) Morphology observation of HaCaT cells and HSFs on surface of collagen membrane cultured for up to 24 h. After 8 hours both cells started to spread on membranes. HaCaT cells grew flattened covering the membrane homogeneously while HSF formed overlapping cell clusters despite of complete covering after 24 hours seeded on membranes. Scale bar =50 μm. (D) The viability of HaCaT cells and HSFs on collagen membranes using live/dead (green/red) assay on day 3. Without red positive cells detected both cells showed high viability on collagen membranes. (Magnification: 100 times). (E) Genes expression (K1, K10 and loricrin) of HaCaT cells in direct or indirect culture system on KGF/COL-E/N. After KGF conjugate gene related to keratinization down regulated to different extends no matter cells were seeded directly on membranes or using transwell system. *Significant difference, p < 0.05 Figure S3. FT-IR spectra of native and EDC/NHS cross linked reconstituted collagen membrane. The broadening of amide A band is noticed in EDC/NHS collagen membrane group compared with collagen. In addition, the wavenumber shifted in the amide I, II and III bands from 1645 to 1638, 1552 to 1553 and 1242 to 1219 cm−1 for native and EDC/NHS cross linked collage. Figure S4. Standard curves for both bFGF and KGF were created during our initial tests. Both curves show a linear relationship between the OD value and concentrations of the corresponding biomolecules Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article. Volume12, Issue6June 2018Pages 1508-1518 RelatedInformation

The dual delivery of KGF and bFGF by collagen membrane to promote skin wound healing