{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,16]],"date-time":"2026-09-16T12:34:30Z","timestamp":1789562070565,"version":"build-2803163510"},"reference-count":52,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T00:00:00Z","timestamp":1741219200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In regard to both natural aging and photoaging caused by UV radiation, a decrease in skin collagen and elastin fibers results in the loss of soft tissue volume. Biodegradable polymer fillers have been used to overcome this problem, but the slow rate of reconstruction and particle agglomeration has limited this approach. The DMSB01 filler, which consists of poly d-l-lactic acid (PDLLA) with a methoxy polyethylene glycol (mPEG) initiator, was created to address this issue. In this study, we assessed the reconstruction and dispersion of the DMSB01 filler in vitro, as well as its effect on collagen expression in rats. DMSB01 showed rapid reconstruction and excellent dispersion stability; gelation occurred within 5 min at 37 \u00b0C and remained stable. In an animal model, DMSB01 induced M2 macrophages, Transforming growth factor beta (TGF-\u03b2) expression, and significantly increased collagens I and III. Collagen recovery and wrinkle improvement were confirmed by the aging and photoaging models, and hematoxylin and eosin (H&amp;E) staining was used to demonstrate the safety and biodegradability of DMSB01. DMSB01 was effective in terms of inducing collagen production and improving skin aging, and shows promise as an innovative ingredient to overcome the limitations of existing fillers.<\/jats:p>","DOI":"10.3390\/ijms26052369","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T09:59:17Z","timestamp":1741255157000},"page":"2369","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Development of a PLA Polymer-Based Liquid Filler for Next-Generation Aesthetics"],"prefix":"10.3390","volume":"26","author":[{"given":"Ji Hyun","family":"Sung","sequence":"first","affiliation":[{"name":"Samyang Holdings Biopharmaceutical Group R&D Center, Seongnam 13488, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na Jeong","family":"Park","sequence":"additional","affiliation":[{"name":"Samyang Holdings Biopharmaceutical Group R&D Center, Seongnam 13488, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeong Eun","family":"Park","sequence":"additional","affiliation":[{"name":"Samyang Holdings Biopharmaceutical Group R&D Center, Seongnam 13488, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hye Sung","family":"Yoon","sequence":"additional","affiliation":[{"name":"Samyang Holdings Biopharmaceutical Group R&D Center, Seongnam 13488, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hyeon","family":"Baek","sequence":"additional","affiliation":[{"name":"Samyang Holdings Biopharmaceutical Group R&D Center, Seongnam 13488, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Helen","family":"Cho","sequence":"additional","affiliation":[{"name":"Samyang Holdings Biopharmaceutical Group R&D Center, Seongnam 13488, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Hoon","family":"Park","sequence":"additional","affiliation":[{"name":"Samyang Holdings Biopharmaceutical Group R&D Center, Seongnam 13488, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,6]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1111\/exd.12852","article-title":"Soft tissue fillers as non-specific modulators of adipogenesis: Change of the paradigm?","volume":"24","author":"Kruglikov","year":"2015","journal-title":"Exp. Dermatol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"140","DOI":"10.1055\/s-2006-947720","article-title":"Injectable treatments for the aging face","volume":"22","author":"Wise","year":"2006","journal-title":"Facial Plast. Surg."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1111\/jocd.12192","article-title":"Women\u2019s attitudes to beauty, aging, and the place of cosmetic procedures: Insights from the QUEST Observatory","volume":"15","author":"Agnes","year":"2016","journal-title":"J. Cosmet. Dermatol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"266","DOI":"10.1007\/s00266-012-0052-6","article-title":"A novel approach to structural facial volume replacement","volume":"37","author":"Sadick","year":"2013","journal-title":"Aesthetic Plast. Surg."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1097\/01.icu.0000243021.20499.4b","article-title":"Dermal filler agents: A practical review","volume":"7","author":"Johl","year":"2006","journal-title":"Curr. Opin. Ophthalmol."},{"key":"ref_6","first-page":"381","article-title":"Dermal fillers: Types, indications, and complications","volume":"101","author":"Candelas","year":"2010","journal-title":"Actas Dermosifiliogr."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"497","DOI":"10.1016\/j.cps.2016.03.002","article-title":"Synthetic fillers for facial rejuvenation","volume":"43","author":"Lee","year":"2016","journal-title":"Clin. Plast. Surg."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"82","DOI":"10.1111\/j.1468-1293.2004.00190.x","article-title":"A randomized open-label study of immediate versus delayed polylactic acid injections for the cosmetic management of facial lipoatrophy in persons with HIV infection","volume":"5","author":"Moyle","year":"2004","journal-title":"HIV Med."},{"key":"ref_9","first-page":"s32","article-title":"The history behind the use of injectable poly-L-lactic acid for facial and nonfacial volumization: The positive impact of evolving methodology","volume":"13","author":"Vleggaar","year":"2014","journal-title":"J. Drugs Dermatol."},{"key":"ref_10","first-page":"759","article-title":"Injectable poly-L-Lactic acid: Understanding its use in the current era","volume":"15","author":"Lorenc","year":"2016","journal-title":"J. Drugs Dermatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1074e","DOI":"10.1097\/PRS.0000000000001247","article-title":"Long-term (24-Month) safety evaluation of poly-DL-lactic acid filler injection for the nasolabial fold: A multicenter, open, randomized, evaluator-blind, active-controlled design","volume":"135","author":"No","year":"2015","journal-title":"Plast. Reconstr. Surg."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Xie, C., Liu, G., Wang, L., Yang, Q., Liao, F., Yang, X., Xiao, B., and Duan, L. (2024). Synthesis and Properties of Injectable Hydrogel for Tissue Filling. Pharmaceutics, 21.","DOI":"10.3390\/pharmaceutics16030430"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1007\/s11095-005-8417-z","article-title":"Thermoresponsive gelatin\/monomethoxy poly(ethylene glycol)-poly(D,L-lactide) hydrogels: Formulation, characterization, and antibacterial drug delivery","volume":"23","author":"Yang","year":"2006","journal-title":"Pharm. Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.jconrel.2010.06.002","article-title":"Thermosensitive hydrogel-containing polymersomes for controlled drug delivery","volume":"15","author":"Lee","year":"2010","journal-title":"J. Control. Release"},{"key":"ref_15","first-page":"16","article-title":"Efficacy and safety of poly-D, L-lactic acid micro-spheres as subdermal fillers in animals","volume":"6","author":"Lin","year":"2019","journal-title":"Plast. Aesthet. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"15317","DOI":"10.1021\/acsami.7b03604","article-title":"Novel Approach of Using Near-Infrared Responsive PEGylated Gold Nanorod Coated Poly(l-Lactide) Microneedles to Enhance the Antitumor Efficiency of Docetaxel-Loaded MPEG-PDLLA Micelles for Treating an A431 Tumor","volume":"9","author":"Hao","year":"2017","journal-title":"ACS Appl. Mater. Interfaces"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1016\/j.jconrel.2020.09.024","article-title":"The Biological Fate of Orally Administered mPEG-PDLLA Polymeric Micelles","volume":"327","author":"He","year":"2020","journal-title":"J. Control. Release"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"2486","DOI":"10.1016\/j.cclet.2021.12.093","article-title":"An injectable mPEG-PDLLA microsphere\/PDLLA-PEG-PDLLA hydrogel composite for soft tissue augmentation","volume":"33","author":"Pan","year":"2022","journal-title":"Chin. Chem. Lett."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Shi, K., Wang, Y.L., Qu, Y., Liao, J.F., Chu, B.Y., Zhang, H.P., Luo, F., and Qian, Z.Y. (2016). Synthesis, characterization, and application of reversible PDLLA-PEG-PDLLA copolymer thermogels in vitro and in vivo. Sci. Rep., 11.","DOI":"10.1038\/srep19077"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1016\/j.addr.2006.09.017","article-title":"Freeze-drying of nanoparticles: Formulation, process and storage considerations","volume":"58","author":"Abdelwashed","year":"2006","journal-title":"Adv. Drug Deliv. Rev."},{"key":"ref_21","first-page":"503","article-title":"Effects of drying methods on physical properties and morphology oftrehalose\/mannitol mixtures","volume":"41","author":"Fransson","year":"2003","journal-title":"Dry. Technol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3670","DOI":"10.1121\/1.5017607","article-title":"Role of freeze-drying in the presence of mannitol on the echogenicity of echogenic liposomes","volume":"142","author":"Kumar","year":"2017","journal-title":"J. Acoust. Soc. Am."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1111\/dth.12299","article-title":"Long-chain polynucleotide filler for skin rejuvenation: Efficacy and complications in five patients","volume":"29","author":"Park","year":"2016","journal-title":"Dermatol. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"333","DOI":"10.1358\/mf.2002.24.6.693065","article-title":"Transforming growth factor-beta 1-induced collagen production in cultures of cardiac fibroblasts is the result of the appearance of myofibroblasts","volume":"24","author":"Lijnen","year":"2002","journal-title":"Comp. Study Methods Find. Exp. Clin. Pharmacol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.xjidi.2023.100222","article-title":"M1\/M2 Macrophage Skewing is Related to Reduction in Types I, V, and VI Collagens with Aging in Sun-Exposed Human Skin","volume":"3","author":"Horiba","year":"2023","journal-title":"JID Innov."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"2382","DOI":"10.1172\/JCI33349","article-title":"Deepening our understanding of immune sentinels in the skin","volume":"117","author":"Nestle","year":"2007","journal-title":"J. Clin. Investig."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"375","DOI":"10.1016\/0531-5565(91)90049-R","article-title":"Age-dependent variations of the biosyntheses of fibronectin and fibrous collagens in mouse skin","volume":"26","author":"Boyer","year":"1991","journal-title":"Exp. Gerontol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1042\/bj2760307","article-title":"Age-related changes in collagen synthesis and degradation in rat tissues","volume":"276","author":"Mays","year":"1991","journal-title":"Biochem. J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"842","DOI":"10.1046\/j.1523-1747.2003.12148.x","article-title":"Collagen Degradation in Aged\/Photodamaged Skin In Vivo and After Exposure to Matrix Metalloproteinase-1 In Vitro","volume":"120","author":"Fligiel","year":"2003","journal-title":"J. Investig. Dermatol."},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Kwon, K.R., Alam, M.B., Park, J.H., Kim, T.H., and Lee, S.H. (2019). Attenuation of UVB-induced photo-aging by polyphenolic-rich spatholobus suberectus stem extract via modulation of MAPK\/AP-1\/MMPs signaling in human keratinocytes. Nutrients, 11.","DOI":"10.3390\/nu11061341"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1874","DOI":"10.1002\/ptr.4943","article-title":"A Comparative Study of Baby Immature and Adult Shoots of Aloe Vera on UVB-Induced Skin Photoaging in vitro","volume":"27","author":"Hwang","year":"2013","journal-title":"Phytother. Res."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"88","DOI":"10.5455\/medarh.2024.78.88-91","article-title":"Comparison of UVA vs UVB Photoaging Rat Models in Short-term Exposure","volume":"78","author":"Mayangsari","year":"2024","journal-title":"Med. Arch."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Kim, H.N., Gil, C.H., Kim, Y.R., Shin, H.K., and Choi, B.T. (2016). Anti-photoaging properties of the phosphodiesterase 3 inhibitor cilostazol in ultraviolet B-irradiated hairless mice. Sci. Rep., 6.","DOI":"10.1038\/srep31169"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1016\/j.bbrc.2019.03.076","article-title":"The effects of HSP27 against UVB-induced photoaging in rat skin","volume":"512","author":"Liu","year":"2019","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/j.maturitas.2011.04.011","article-title":"Molecular aspects of skin ageing","volume":"69","author":"Naylor","year":"2011","journal-title":"Maturitas"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1016\/S0040-8166(02)00101-5","article-title":"Cell-matrix interactions of in vitro human skin fibroblasts upon addition of hyaluronan","volume":"35","author":"Boraldi","year":"2003","journal-title":"Tissue Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1459","DOI":"10.1007\/s00417-012-2087-4","article-title":"Cytoprotectiveeffect of hyaluronic acid and hydroxypropyl methylcellulose against DNA damage induced by thimerosal in Chang conjunctival cells","volume":"250","author":"Ye","year":"2012","journal-title":"Graefes Arch. Clin. Exp. Ophthalmol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"2670","DOI":"10.1016\/j.fct.2011.07.020","article-title":"Antioxidant activity of low molecular weight hyaluronic acid","volume":"49","author":"Ke","year":"2011","journal-title":"Food Chem. Toxicol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1001\/archderm.143.2.155","article-title":"In vivo stimulation of de novo collagen production caused by cross-linked hyaluronic acid dermal filler injections in photodamaged human skin","volume":"143","author":"Wang","year":"2007","journal-title":"Arch. Dermatol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"579","DOI":"10.1111\/wrr.12214","article-title":"Hyaluronan in wound healing: Rediscovering a major player","volume":"22","author":"Aya","year":"2014","journal-title":"Wound Repair. Regen."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Li, H., Xu, X., Wu, L., Chen, X., Akhter, H., Wang, Y., Song, P., Liao, X., Zhang, Z., and Li, Z. (2023). Recent progress and clinical applications of advanced biomaterials in cosmetic surgery. Regen. Biomater., 10.","DOI":"10.1093\/rb\/rbad005"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1055\/s-0029-1220648","article-title":"Sculptra: A stimulatory filler","volume":"25","author":"Lacombe","year":"2009","journal-title":"Facial Plast. Surg."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"S13","DOI":"10.1093\/asj\/sjy012","article-title":"Physiochemical characteristics of poly-L-lactic acid (PLLA)","volume":"38","author":"Fitzgerald","year":"2018","journal-title":"Aesthet. Surg. J."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2453","DOI":"10.1016\/j.biomaterials.2009.11.115","article-title":"A biodegradable, injectable, gel system based on MPEG-b-(PCL-ran-PLLA) diblock copolymers with an adjustable therapeutic window","volume":"31","author":"Kang","year":"2010","journal-title":"Biomaterials"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2748","DOI":"10.1016\/j.biomaterials.2013.01.006","article-title":"Injectable intratumoral hydrogel as 5-fluorouracil drug depot","volume":"34","author":"Seo","year":"2013","journal-title":"Biomaterials"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Oh, S., Seo, S.B., Kim, G., Batsukh, S., Park, C.H., Son, K.H., and Byun, K. (2023). Poly-D,L-Lactic Acid Filler Increases Extracellular Matrix by Modulating Macrophages and Adipose-Derived Stem Cells in Aged Animal Skin. Antioxidants, 1.","DOI":"10.3390\/antiox12061204"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Kim, J.H., Kwon, T.R., Lee, S.E., Jang, Y.N., Han, H.S., Mun, S.K., and Kim, B.J. (2020). Comparative evaluation of the effectiveness of novel hyaluronic acid-polynucleotide complex dermal filler. Sci. Rep., 10.","DOI":"10.1038\/s41598-020-61952-w"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"187","DOI":"10.1016\/j.cjprs.2022.09.015","article-title":"Polydeoxyribonucleotide: A promising skin anti-aging agent","volume":"4","author":"Khan","year":"2022","journal-title":"Chin. J. Plast. Reconstr. Surg."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/0378-5173(95)04258-X","article-title":"In vitro degradation of nanospheres from poly(D,L-lactides) of different molecular weights and polydispersities","volume":"129","author":"Belbella","year":"1996","journal-title":"Int. J. Pharm."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1016\/0168-3659(94)00100-9","article-title":"Chain-end scission in acid catalyzed hydrolysis of poly (D,L-lactide) in solution","volume":"34","author":"Shih","year":"1995","journal-title":"J. Control. Release"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1016\/j.foodcont.2014.06.024","article-title":"Surface physiological changes induced by lactic acid on pathogens in consideration of pKa and pH","volume":"46","author":"Wang","year":"2014","journal-title":"Food Control"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"71","DOI":"10.1016\/j.cacc.2006.05.006","article-title":"Lactate\u2014The bad boy of metabolism, or simply misunderstood","volume":"17","author":"Handy","year":"2006","journal-title":"Curr. Anaesth. Crit. Care"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/2369\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:48:27Z","timestamp":1760028507000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/26\/5\/2369"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,6]]},"references-count":52,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["ijms26052369"],"URL":"https:\/\/doi.org\/10.3390\/ijms26052369","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,6]]}}}