{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:55:27Z","timestamp":1790618127664,"version":"4.1.0"},"reference-count":55,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:00:00Z","timestamp":1790380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Beijing Natural Science Foundation","doi-asserted-by":"publisher","award":["L234021"],"award-info":[{"award-number":["L234021"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Placental extracts are rich in bioactive molecules and exhibit broad reparative properties, yet the molecular constituents responsible for their effects on skin tissue repair remain insufficiently characterized. In this study, we employed a cell-surface affinity-based screening approach using dermal fibroblasts (BJ) and microvascular endothelial (HMEC-1) cells as dual biological baits to capture bioactive peptides directly from placental extracts. Through liquid chromatography\u2013tandem mass spectrometry (LC-MS\/MS) analysis and background subtraction, a peptide with dual-cell targeting potential, GPPVSE, was identified. In vitro, GPPVSE significantly promoted the viability, proliferation and migration of both BJ and HMEC-1 cells and enhanced endothelial tube formation. In vivo, topical 20 \u03bcM GPPVSE in a mouse full-thickness skin defect model achieved an 84.7% wound closure rate by day 8, outperforming both phosphate-buffered saline (PBS) and epidermal growth factor (EGF) groups. Histological analysis revealed that GPPVSE promoted granulation tissue maturation, strengthened epidermal\u2013dermal junction integrity, and enhanced regeneration of skin appendages, including hair follicles and sebaceous glands, during the remodeling phase. Collectively, GPPVSE provides valuable molecular insights into the reparative activity of placental extracts and establishes a potentially adaptable cell-based paradigm for mining functional peptides from complex natural sources.<\/jats:p>","DOI":"10.3390\/ijms27198617","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:50:54Z","timestamp":1790614254000},"page":"8617","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Identification of a Novel Placental Peptide with Skin Reparative Properties by Cell-Surface Affinity Screening"],"prefix":"10.3390","volume":"27","author":[{"given":"Fangyu","family":"Xing","sequence":"first","affiliation":[{"name":"State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China"},{"name":"School of Chemical Engineering, University of Chinese Academy of Sciences, Beijing 100049, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2470-3160","authenticated-orcid":false,"given":"Jianping","family":"Gao","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Zhenhu","family":"Guo","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Yingjun","family":"Kong","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"investigation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Guifeng","family":"Zhang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Biopharmaceutical Preparation and Delivery, Institute of Process Engineering, Chinese Academy of Sciences, Beijing 100190, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4837930","DOI":"10.1155\/2018\/4837930","article-title":"Placenta and Placental Derivatives in Regenerative Therapies: Experimental Studies, History, and Prospects","volume":"2018","author":"Pogozhykh","year":"2018","journal-title":"Stem Cells Int."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Protzman, N.M., Mao, Y., Long, D.S.R., Sivalenka, R., Gosiewska, A., Hariri, R.J., and Brigido, S.A. (2023). Placental-Derived Biomaterials and Their Application to Wound Healing: A Review. Bioengineering, 10.","DOI":"10.20944\/preprints202306.0211.v1"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1016\/j.actbio.2025.07.028","article-title":"Unlocking the regenerative properties of extraembryonic membrane-derived biomaterials in tissue engineering","volume":"203","author":"Almeida","year":"2025","journal-title":"Acta Biomater."},{"key":"ref_4","first-page":"434","article-title":"Human placenta hydrolysates: From V.P. Filatov to the present day: Review","volume":"94","author":"Gromova","year":"2022","journal-title":"Ter. Arkh."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Huang, L., Chin, L.C., Kimura, K., and Nakahata, Y. (2022). Human Placental Extract Delays In Vitro Cellular Senescence through the Activation of NRF2-Mediated Antioxidant Pathway. Antioxidants, 11.","DOI":"10.3390\/antiox11081545"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"e00416","DOI":"10.1016\/j.heliyon.2017.e00416","article-title":"Placental extract ameliorates non-alcoholic steatohepatitis (NASH) by exerting protective effects on endothelial cells","volume":"3","author":"Yamauchi","year":"2017","journal-title":"Heliyon"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"126929","DOI":"10.1016\/j.ijbiomac.2023.126929","article-title":"A novel multifunctional chitosan-gelatin\/carboxymethyl cellulose-alginate bilayer hydrogel containing human placenta extract for accelerating full-thickness wound healing","volume":"253","author":"Seifi","year":"2023","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"98","DOI":"10.1186\/s13223-023-00850-y","article-title":"Human placental extract suppresses mast cell activation and induces mast cell apoptosis","volume":"19","author":"Wu","year":"2023","journal-title":"Allergy Asthma Clin. Immunol."},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Alimu, Y., Yamamoto, T., and Nakahata, Y. (2025). Biological effects of human placental extracts-variations in manufacturing methods and compositions. Front. Pharmacol., 16.","DOI":"10.3389\/fphar.2025.1707890"},{"key":"ref_10","first-page":"456","article-title":"The revolutionary role of placental derivatives in biomedical research","volume":"49","author":"Moghassemi","year":"2025","journal-title":"Bioact. Mater."},{"key":"ref_11","first-page":"1","article-title":"Placental therapy: An insight to their biological and therapeutic properties","volume":"1","author":"Pan","year":"2017","journal-title":"J. Med. Ther."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Shen, L.H., Fan, L., Zhang, Y., Zhu, Y.K., Zong, X.L., Peng, G.N., and Cao, S.Z. (2022). Protective Effect and Mechanism of Placenta Extract on Liver. Nutrients, 14.","DOI":"10.3390\/nu14235071"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"322","DOI":"10.21037\/atm.2019.10.20","article-title":"Human placental extract: A potential therapeutic in treating osteoarthritis","volume":"11","author":"Gwam","year":"2023","journal-title":"Ann. Transl. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"11031","DOI":"10.1038\/s41598-022-15270-y","article-title":"Human placental extract activates a wide array of gene expressions related to skin functions","volume":"12","author":"Chang","year":"2022","journal-title":"Sci. Rep."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1046\/j.1365-2133.2003.05164.x","article-title":"Wound healing effects of porcine placental extracts on rats with thermal injury","volume":"148","author":"Wu","year":"2003","journal-title":"Br. J. Dermatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2062","DOI":"10.1039\/D1BM01891D","article-title":"Fabrication and characterization of a pro-angiogenic hydrogel derived from the human placenta","volume":"10","author":"Chao","year":"2022","journal-title":"Biomater. Sci."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Nensat, C., Songjang, W., Tohtong, R., Suthiphongchai, T., Phimsen, S., Rattanasinganchan, P., Metheenukul, P., Kumphune, S., and Jiraviriyakul, A. (2021). Porcine placenta extract improves high-glucose-induced angiogenesis impairment. BMC Complement. Med. Ther., 21.","DOI":"10.1186\/s12906-021-03243-z"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Xiao, H., Jiang, H., Tu, H., Jia, Y., Wang, H., Lu, X., Fang, R., and Xiao, G. (2022). Extraction, Isolation and Identification of Low Molecular Weight Peptides in Human Milk. Foods, 11.","DOI":"10.3390\/foods11131836"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"148592","DOI":"10.1016\/j.foodchem.2026.148592","article-title":"Decoding salty peptides from pea protein: Isolation, characterization, and structure-activity relationship","volume":"510","author":"Fu","year":"2026","journal-title":"Food Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"19844","DOI":"10.1039\/D0RA02644A","article-title":"Isolation of antioxidant peptides from yak casein hydrolysate","volume":"10","author":"Liu","year":"2020","journal-title":"RSC Adv."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"2315","DOI":"10.1021\/jacs.2c10903","article-title":"Chemically Synthetic Membrane Receptors Establish Cells with Artificial Sense-and-Respond Signaling Pathways","volume":"145","author":"Wu","year":"2023","journal-title":"J. Am. Chem. Soc."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8301","DOI":"10.1038\/s41467-023-43931-7","article-title":"Proximity extracellular protein-protein interaction analysis of EGFR using AirID-conjugated fragment of antigen binding","volume":"14","author":"Yamada","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Ito, T., Kasai, Y., Kumagai, Y., Suzuki, D., Ochiai-Noguchi, M., Irikura, D., Miyake, S., and Murakami, Y. (2018). Quantitative Analysis of Interaction Between CADM1 and Its Binding Cell-Surface Proteins Using Surface Plasmon Resonance Imaging. Front. Cell Dev. Biol., 6.","DOI":"10.3389\/fcell.2018.00086"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"94","DOI":"10.1007\/s10735-025-10368-9","article-title":"Molecular roles in membrane receptor signaling pathways and cascade reactions in chondrocytes: A review","volume":"56","author":"Zhu","year":"2025","journal-title":"J. Mol. Histol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1153","DOI":"10.1042\/BCJ20160095","article-title":"The leucine-rich repeat protein PRELP binds fibroblast cell-surface proteoglycans and enhances focal adhesion formation","volume":"473","author":"Bengtsson","year":"2016","journal-title":"Biochem. J."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"198","DOI":"10.1161\/01.ATV.0000053846.71621.93","article-title":"Molecular basis of cell membrane estrogen receptor interaction with phosphatidylinositol 3-kinase in endothelial cells","volume":"23","author":"Simoncini","year":"2003","journal-title":"Arterioscler. Thromb. Vasc. Biol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"1647","DOI":"10.1007\/s00216-024-05166-3","article-title":"Development of target-based cell membrane affinity ultrafiltration technology for a simplified approach to discovering potential bioactive compounds in natural products","volume":"416","author":"Chen","year":"2024","journal-title":"Anal. Bioanal. Chem."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"104002","DOI":"10.1016\/j.jprot.2020.104002","article-title":"A novel platform for peptide-mediated affinity capture and LC-MS\/MS identification of host receptors involved in Plasmodium invasion","volume":"231","author":"Plaza","year":"2021","journal-title":"J. Proteom."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"2201010","DOI":"10.1002\/jssc.202201010","article-title":"System to screen and purify active ingredients from herbal medicines using hydrogel-modified human umbilical vein endothelial cell membrane chromatography coupled with semi-preparative high-performance liquid chromatography-offline-high-performance liquid chromatography-mass spectrometry","volume":"46","author":"Huang","year":"2023","journal-title":"J. Sep. Sci."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"11838","DOI":"10.1073\/pnas.0602615103","article-title":"Aptamers evolved from live cells as effective molecular probes for cancer study","volume":"103","author":"Shangguan","year":"2006","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.1021\/acs.biochem.2c00105","article-title":"An In Vitro Selection Platform to Identify Multiple Aptamers against Multiple Cell-Surface Markers Using Ligand-Guided Selection","volume":"61","author":"Williams","year":"2022","journal-title":"Biochemistry"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"e81398","DOI":"10.7554\/eLife.81398","article-title":"Identification of orphan ligand-receptor relationships using a cell-based CRISPRa enrichment screening platform","volume":"11","author":"Siepe","year":"2022","journal-title":"eLife"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"119667","DOI":"10.1016\/j.biomaterials.2019.119667","article-title":"Chemical functionality of multidomain peptide hydrogels governs early host immune response","volume":"231","author":"Leach","year":"2020","journal-title":"Biomaterials"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"e202400554","DOI":"10.1002\/jssc.202400554","article-title":"Greening Separation and Purification of Proteins and Peptides","volume":"47","author":"Marakova","year":"2024","journal-title":"J. Sep. Sci."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1007\/s10989-020-10119-2","article-title":"Optimization of Ultrafiltration Membrane Separation Technology and Characterization of Peptides from Bovine Bone Marrow","volume":"27","author":"Rozi","year":"2021","journal-title":"Int. J. Pept. Res. Ther."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Sadiq, A., Khumalo, N.P., and Bayat, A. (2024). Development and validation of novel keloid-derived immortalized fibroblast cell lines. Front. Immunol., 15.","DOI":"10.3389\/fimmu.2024.1326728"},{"key":"ref_37","first-page":"1000","article-title":"Immortalization of Cultured Cells in Regenerative Biomedicine: Approaches, Opportunities, and Limitations","volume":"90","author":"Primak","year":"2025","journal-title":"Biochemistry"},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Suali, L., Chia, Y., Rustin, C., Lem, F.F., Ching, X.J., Mansur, M.A.B., Henry, Z.A., Chan, M.K.S., Wong, M.B.F., and Pan, S.Y. (2026). Primary cell cultures versus immortalized cell lines: Critical comparative insights into biological fidelity and translational applications. Biotech. Histochem., early access.","DOI":"10.1080\/10520295.2026.2714776"},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Glazieva, V.S., Alexandrushkina, N.A., Nimiritsky, P.P., Kulebyakina, M.A., Eremichev, R.Y., and Makarevich, P.I. (2023). Extracellular Matrix Deposition Defines the Duration of Cell Sheet Assembly from Human Adipose-Derived MSC. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms242317050"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2438","DOI":"10.1021\/acsbiomaterials.2c01566","article-title":"In Vitro Profiling of the Extracellular Matrix and Integrins Expressed by Human Corneal Endothelial Cells Cultured on Silk Fibroin-Based Matrices","volume":"9","author":"Hazra","year":"2023","journal-title":"ACS Biomater. Sci. Eng."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"eaec9801","DOI":"10.1126\/sciadv.aec9801","article-title":"Linker histone H1 functions as a liquid-like glue to organize chromatin in living human cells","volume":"12","author":"Shimazoe","year":"2026","journal-title":"Sci. Adv."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Lokeswara, A.W., Hiksas, R., Irwinda, R., and Wibowo, N. (2021). Preeclampsia: From Cellular Wellness to Inappropriate Cell Death, and the Roles of Nutrition. Front. Cell Dev. Biol., 9.","DOI":"10.3389\/fcell.2021.726513"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1055\/s-0040-1722225","article-title":"NETosis Markers in Pregnancy: Effects Differ According to Histone Subtypes","volume":"121","author":"Bouvier","year":"2021","journal-title":"Thromb. Haemost."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"3557","DOI":"10.1016\/j.jtha.2023.08.023","article-title":"Design and characterization of novel activated protein C variants for the proteolysis of cytotoxic extracellular histone H3","volume":"21","author":"Huckriede","year":"2023","journal-title":"J. Thromb. Haemost."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"92","DOI":"10.1186\/s12958-023-01138-x","article-title":"Expression and significance of cathepsin C and cathepsin D during pregnancy and Preeclampsia","volume":"21","author":"Song","year":"2023","journal-title":"Reprod. Biol. Endocrinol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1080\/713611042","article-title":"Peptides and hormesis","volume":"33","author":"Calabrese","year":"2003","journal-title":"Crit. Rev. Toxicol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1080\/17460441.2021.1838483","article-title":"Bi-phasic dose response in the preclinical and clinical developments of sigma-1 receptor ligands for the treatment of neurodegenerative disorders","volume":"16","author":"Maurice","year":"2021","journal-title":"Expert Opin. Drug Discov."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"3390","DOI":"10.2174\/138161210793563491","article-title":"Concepts for Biologically Active Peptides","volume":"16","author":"Abba","year":"2010","journal-title":"Curr. Pharm. Des."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"4497","DOI":"10.1016\/j.csbj.2023.09.022","article-title":"Family-wide analysis of integrin structures predicted by AlphaFold2","volume":"21","author":"Zhang","year":"2023","journal-title":"Comput. Struct. Biotechnol. J."},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Park, E., Kim, H.G., Un, Y., and Oh, E.S. (2025). Spatial and Functional Roles of Syndecans in Skin Wound Healing. Int. J. Mol. Sci., 26.","DOI":"10.3390\/ijms262110571"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1186\/s40001-017-0299-0","article-title":"Chemokine ligand-receptor interactions critically regulate cutaneous wound healing","volume":"23","author":"Hoff","year":"2018","journal-title":"Eur. J. Med. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1111\/j.1600-0625.2010.01184.x","article-title":"Role of protease-activated receptors in human skin fibrosis and scleroderma","volume":"20","author":"Cevikbas","year":"2010","journal-title":"Exp. Dermatol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1038\/s41580-024-00715-1","article-title":"Cellular and molecular mechanisms of skin wound healing","volume":"25","author":"Martin","year":"2024","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"589","DOI":"10.1016\/j.jaad.2015.08.068","article-title":"Wound healing and treating wounds: Differential diagnosis and evaluation of chronic wounds","volume":"74","author":"Morton","year":"2016","journal-title":"J. Am. Acad. Dermatol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4052","DOI":"10.1039\/D0BM00266F","article-title":"Vascularization strategies for skin tissue engineering","volume":"8","author":"Amirsadeghi","year":"2020","journal-title":"Biomater. Sci."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8617\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T16:56:47Z","timestamp":1790614607000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/19\/8617"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,26]]},"references-count":55,"journal-issue":{"issue":"19","published-online":{"date-parts":[[2026,10]]}},"alternative-id":["ijms27198617"],"URL":"https:\/\/doi.org\/10.3390\/ijms27198617","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,26]]}}}