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Current treatment modalities, including compression therapy, pharmacological agents, radiation, silicone gel, and laser therapies, have faced limitations primarily due to inadequate drug penetration into the dense fibrotic scar tissue. In this context, microneedle-mediated controlled delivery systems have emerged as a promising pharmaceutical platform to enhance localized and sustained delivery of therapeutic agents, including small-molecule drugs, biologic proteins, small interfering RNA, and living cells, directly into HS. This article critically reviews the biological and formulation-related challenges associated with transdermal delivery in scar tissue and highlights recent innovations in microneedle design, material selection, and drug-loading techniques tailored for controlled release applications. Furthermore, it discusses the integration of proteins and cell-based therapies within microneedle platforms and their potential to modulate scar remodeling and inflammation. By addressing current limitations and exploring cutting-edge technologies, this review article aims to guide the development of effective microneedle-mediated strategies for pharmaceutical intervention in hypertrophic scar management.<\/jats:p>","DOI":"10.1093\/burnst\/tkag025","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T11:05:03Z","timestamp":1773831903000},"source":"Crossref","is-referenced-by-count":0,"title":["Advances in microneedle design for the delivery of drugs, proteins, and cells in the treatment of hypertrophic scars"],"prefix":"10.1093","volume":"14","author":[{"given":"Juntong","family":"Guo","sequence":"first","affiliation":[{"name":"School of Pharmacy, Nanjing University of Chinese Medicine , 138 Xianlin Road, Nanjing 210023 ,","place":["PR China"]},{"name":"Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application, Nanjing University of Chinese Medicine , 138 Xianlin Road, Nanjing 210023 ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qinghan","family":"Tang","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Nanjing Hospital of Chinese Medicine , 157 Daming Road, Nanjing 210022, Jiangsu ,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhengping","family":"Ge","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanjing University of Chinese Medicine , 138 Xianlin Road, Nanjing 210023 ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Xia","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanjing University of Chinese Medicine , 138 Xianlin Road, Nanjing 210023 ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hanmei","family":"Liu","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Nanjing University of Chinese Medicine , 155 Hanzhong Road, Nanjing 210000 ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Huaikai","family":"Shi","sequence":"additional","affiliation":[{"name":"Asbestos and Dust Diseases Research Institute, Concord Hospital , Gate 3 Hospital Road, Sydney, NSW 2138 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinlong","family":"Huang","sequence":"additional","affiliation":[{"name":"Affiliated Hospital of Nanjing University of Chinese Medicine , 155 Hanzhong Road, Nanjing 210000 ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmacy, Nanjing University of Chinese Medicine , 138 Xianlin Road, Nanjing 210023 ,","place":["PR China"]},{"name":"Jiangsu Provincial Engineering Research Center of TCM External Medication Development and Application, Nanjing University of Chinese Medicine , 138 Xianlin Road, Nanjing 210023 ,","place":["PR China"]},{"name":"Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization, 138 Xianlin Road, Nanjing University of Chinese Medicine , Nanjing 210023 ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark S","family":"Cooper","sequence":"additional","affiliation":[{"name":"Adrenal Steroid Group, ANZAC Research Institute, Concord Hospital, The University of Sydney , Gate 3, Hospital Road, Sydney, NSW 2137 ,","place":["Australia"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xin","family":"Yan","sequence":"additional","affiliation":[{"name":"Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University , 321 Zhongshan Road, Nanjing 21000 ,","place":["PR 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210023 ,","place":["PR China"]},{"name":"Department of Burns and Plastic Surgery, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University , 321 Zhongshan Road, Nanjing 21000 ,","place":["PR China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"2026061513251328500_ref1","journal-title":"Laser management of scars."},{"key":"2026061513251328500_ref2","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1186\/s12929-024-01001-0","article-title":"TEM1\/endosialin\/CD248 promotes pathologic scarring and TGF-\u03b2 activity through its receptor stability in dermal fibroblasts","volume":"31","author":"Hong","year":"2024","journal-title":"J Biomed Sci"},{"key":"2026061513251328500_ref3","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1038\/s41572-023-00474-x","article-title":"Scars","volume":"9","author":"Jeschke","year":"2023","journal-title":"Nat Rev Dis 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