Potential of Secretome Hydrogel for Wound Healing in LPS- and Scratch-Induced BJ Cells as an Inflammation Model
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Keywords:
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Anti-Inflammatory, Fibroblast, Hydrogel, Regeneration, Secretome, Cells Migration
Abstract
Wound healing often requires specialized interventions to accelerate recovery due to prolonged inflammation and limited regenerative factors. Umbilical Cord Mesenchymal Stem Cells secretome (UCMSCs) comprises various cytokines and growth factors that can promote wound healing. This study aims to analyze the potential of a secretome-based hydrogel as a wound-healing agent using BJ fibroblast cells induced by lipopolysaccharide (LPS) and scratch injury as an inflammation model. The secretome hydrogel was formulated using Carbopol, Hydroxypropyl Methylcellulose (HPMC), Hydroxyethyl Cellulose (HEC), and secretome. Cytotoxicity was conducted using the WST-8 assay, while cell migration was evaluated through a scratch assay. Tumor Necrosis Factor-???? (TNF-????), Nuclear Factor kappa-B (NF-????B), and Interleukin-8 (IL-8) gene expression were analyzed via qRT-PCR. Additionally, malondialdehyde (MDA) levels were measured for oxidative stress assessment, whereas Connective Tissue Growth Factor (CTGF) and Transforming Growth Factor-????1 (TGF-????1) levels were quantified using ELISA and colorimetric assays. The secretome hydrogel exhibited no cytotoxic effects on BJ fibroblast cells and significantly enhanced cell migration. Moreover, it reduced the TNF-????, IL-8, and NF-????B expression, indicating anti-inflammatory activity. The hydrogel also decreased MDA levels while increasing TGF-β1 and CTGF expression, suggesting antioxidant properties and enhanced tissue regeneration in the inflammatory model. The secretome-based hydrogel presents a promising therapeutic approach for promoting chronic wound healing by modulating inflammation, reducing oxidative stress, enhancing tissue regeneration, and stimulating fibroblast migration.
References
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Kwon, J. (2023). Mesenchymal Stem Cell-Derived Secretomes Enriched Alginate/Extracellular Matrix Hydrogel Patch Accelerates Skin Wound Healing. Biomaterials Research, 27(1); 107.
Li, Q., D. Wang, Z. Jiang, R. Li, T. Xue, C. Lin, and B. Sun (2022). Advances of Hydrogel Combined with Stem Cells in Promoting Chronic Wound Healing. Frontiers in Chemistry, 10; 1038839.
Ma, H., P. Lam, W. Siu, C. Tong, K. Lo, C. Koon, and P. Leung (2021). Adipose Tissue-Derived Mesenchymal Stem Cells (ADMSCs) and ADMSC-Derived Secretome Expedited Wound Healing in a Rodent Model – A Preliminary Study. Clinical Cosmetic and Investigational Dermatology, 14; 753–764.
Monfared, G. S., P. Ertl, and M. Rothbauer (2020). An On-Chip Wound Healing Assay Fabricated by Xurography for Evaluation of Dermal Fibroblast Cell Migration and Wound Closure. Scientific Reports, 10; 16192.
Monika, P., M. N. Chandraprabha, A. Rangarajan, P. V. Waiker, and M. K. N. Chidambara (2022). Challenges in Healing Wound: Role of Complementary and Alternative Medicine. Frontiers in Nutrition, 20(8); 791899.
Natallya, F., N. Herwanto, C. Prakoeswa, D. Indramaya, and F. Rantam (2019). Effective Healing of Leprosy Chronic Plantar Ulcers by Application of Human Amniotic Membrane Stem Cell Secretome Gel. Indian Journal of Dermatology, 64(3); 250.
Noh, K., X. Liu, Z. Zhong, C. Yang, Y. Kim, G. Lee, and K. Kim (2018). Leukocyte-Poor Platelet-Rich Plasma-Derived Growth Factors Enhance Human Fibroblast Proliferation in Vitro. Clinics in Orthopedic Surgery, 10(2); 240.
Nuraini, S., S. Saadah, and S. Rismawati (2019). The Effect of Breastmilk Topical on Perineal Wound Healing on 1–7 Days Postpartum Mother. Midwifery and Nursing Research, 1(2); 68.
Qu, F., F. Guilak, and R. L. Mauck (2019). Cell Migration: Implications for Repair and Regeneration in Joint Disease. Nature Reviews Rheumatology, 15(3); 167–179.
Rozirwan, A., Siswanto, N. N. Khotimah, R. Y. Nugroho, W. A. E. Putri, and R. Apri (2024). Anti-Inflammatory Activity and Phytochemical Profile from the Leaves of the Mangrove Sonneratia Caseolaris (L.) Engl. for Future Drug Discovery. Science and Technology Indonesia, 9(2); 502–516.
Saheli, M., M. Bayat, R. Ganji, F. Hendudari, R. Kheirjou, M. Pakzad, B. Najar, and A. Piryaei (2020). Human Mesenchymal Stem Cells-Conditioned Medium Improves Diabetic Wound Healing Mainly Through Modulating Fibroblast Behaviors. Archives of Dermatological Research, 312(5); 325–336.
Sarfraz, M., R. Iqbal, K. U. Khan, and M. U. Minhas (2022). Carbopol Based Hydrogels for Itopride Hydrochloride Delivery; Synthesis, Characterization and Comparative Assessment with Various Monomers. Journal of Functional Biomaterials, 13(4); 295.
Simader, E., D. Traxler, M. Kasiri, H. Hofbauer, M. Wolzt, C. Glogner, and H. Ankersmit (2017). Safety and Tolerability of Topically Administered Autologous, Apoptotic PBMC Secretome (Aposec) in Dermal Wounds: A Randomized Phase 1 Trial (MARSYAS I). Scientific Reports, 7(1).
Suhail, M., J. Y. Liu, M. C. Hung, I. H. Chiu, M. U. Minhas, and P. C. Wu (2022). Preparation, In Vitro Characterization, and Cytotoxicity Evaluation of Polymeric pH-Responsive Hydrogels for Controlled Drug Release. Pharmaceutics, 14(9); 1864.
Sutjiatmo, A. B., W. Widowati, I. Sumiati, T. Priestu, S. Arumwardana, H. S. W. Kusuma, and A. M. Azizah (2021). Antioxidant and Anticancer Potential of Raja Bulu Banana Peel and Heart (Musa Acuminata Colla (AAB Group)) Ethanol Extracts in MCF-7 Cell Lines. Majalah Obat Tradisional, 26(1); 49–58.
Tan, S., P. Aisyah, Y. Firmansyah, N. Nathasia, E. Budi, and S. Hendrawan (2023). Effectiveness of Secretome from Human Umbilical Cord Mesenchymal Stem Cells in Gel (10% SM-hUCMSC Gel) for Chronic Wounds (Diabetic and Trophic Ulcer) – Phase 2 Clinical Trial. Journal of Multidisciplinary Healthcare, 16; 1763–1777.
Wei, Y., J. Li, Y. Huang, X. Lei, L. Zhang, M. Yin, and J. Wu (2022). The Clinical Effectiveness and Safety of Using Epidermal Growth Factor, Fibroblast Growth Factor and Granulocyte-Macrophage Colony Stimulating Factor as Therapeutics in Acute Skin Wound Healing: A Systematic Review and Meta-Analysis. Burns & Trauma, 10; tkac002.
Widowati, W., A. Faried, R. F. Guannegara, F. Raharrdja, F. H. Zahirof, F. A. Sutendi, F. S. Nindya, K. Azis, and R. K. Ekajaya (2024). The Potential of Human Wharton’s Jelly Mesenchymal Stem Cells Secretome-Based Topical Gel for Therapeutic Application. Avicenna Journal of Medical Biotechnology, 16(4); 233–243.
Yamakawa, S. and K. Hayashida (2019). Advances in Surgical Applications of Growth Factors for Wound Healing. Burns & Trauma, 7; s41038–019–0148–1.
Yu, J., S. Choi, J. Um, and K. Park (2017). Reduced Expression of YAP in Dermal Fibroblasts Is Associated with Impaired Wound Healing in Type 2 Diabetic Mice. Tissue Engineering and Regenerative Medicine, 14(1); 49–55.
Zhang, H., W. Li, S. Tang, Y. Chen, L. Lan, S. Li, and G. Jiang (2023). A Boron-Based Probe Driven Theranostic Hydrogel Dressing for Visual Monitoring and Matching Chronic Wound Healing. Advanced Functional Materials, 33(51); 2305580.
Zulharini, M., I. R. Sutejo, H. Fadliyah, and R. I. Jenie (2018). Methanolic Extract of Red Betel Leaves (Piper crocatum Ruiz & Pav) Perform Cytotoxic Effect and Antimigration Activity Toward Metastatic Breast Cancer. Indonesian Journal of Cancer Chemoprevention, 8(3); 94–100.
Boido, M., M. Ghibaudi, P. Gentile, E. Favaro, R. Fusaro, and C. Tonda-Turo (2019). Chitosan-Based Hydrogel to Support the Paracrine Activity of Mesenchymal Stem Cells in Spinal Cord Injury Treatment. Scientific Reports, 9; 6402.
Chen, H., R. Shi, B. Luo, X. Yang, L. Qiu, J. Xiong, and Y. Wu (2015). Macrophage Peroxisome Proliferator-Activated Receptor ???? Deficiency Delays Skin Wound Healing Through Impairing Apoptotic Cell Clearance in Mice. Cell Death and Disease, 6(1); e1597.
Dedier, M., B. Magne, M. Nivet, S. Banzet, and M. Trouillas (2023). Anti-Inflammatory Effect of Interleukin-6 Highly Enriched in Secretome of Two Clinically Relevant Sources of Mesenchymal Stromal Cells. Frontiers in Cell and Developmental Biology, 11; 1244120.
Deshpande, R., M. Kanitkar, S. Kadam, K. Dixit, H. Chhabra, J. Bellare, and V. Kale (2018). Matrix-Entrapped Cellular Secretome Rescues Diabetes-Induced EPC Dysfunction and Accelerates Wound Healing in Diabetic Mice. PLOS One, 13(8); e0202510.
Doshi, R. B., D. Vakil, T. G. Molley, M. S. Islam, K. A. Kilian, C. Cunningham, and K. S. Sidhu (2024). Mesenchymal Stem Cell-Secretome Laden Photopolymerizable Hydrogels for Wound Healing. Journal of Biomedical Materials Research Part A, 112(9); 1484–1493.
El-Sawah, S. G., F. Althobaiti, A. Aldhahrani, E. Fayad, M. A. Abdel-Dayem, R. M. Amen, E. S. Shabana, E. I. El-Hallous, and H. M. Rashwan (2021). Investigation of the Antioxidant Defensive Role of Both AD-MSCs and BM-MSCs in Modulating the Alteration in the Oxidative Stress Status in Various STZ-Diabetic Rats’ Tissues. Biocell, 45(6); 1561–1568.
Fadini, G., M. Albiero, R. Millioni, N. Poncina, M. Rigato, R. Scotton, and A. Avogaro (2014). The Molecular Signature of Impaired Diabetic Wound Healing Identifies SERPINB3 as a Healing Biomarker. Diabetologia, 57(9); 1947–1956.
Frykberg, R. G. and J. Banks (2015). Challenges in the Treatment of Chronic Wounds. Advances in Wound Care (New Rochelle), 4(9); 560–582.
Hassan, W., U. Greiser, and W. Wang (2014). Role of Adipose-Derived Stem Cells in Wound Healing. Wound Repair and Regeneration, 22(3); 313–325.
Hong, J. and S. Park (2012). The Combined Effect of Recombinant Human Epidermal Growth Factor and Erythropoietin on Full-Thickness Wound Healing in Diabetic Rat Model. International Wound Journal, 11(4); 373–378.
Keshava, R. and R. Gope (2015). Sodium Butyrate Plus EGF and PDGF-BB Aids Cutaneous Wound Healing in Diabetic Mice. Advances in Biology; 1–10.
Kim, J., K. Lee, S. Han, E. Ko, D. Yoon, I. Park, and J. Lee (2021). Development of Stabilized Dual Growth Factor-Loaded Hyaluronate Collagen Dressing Matrix. Journal of Tissue Engineering, 12; 2041731421999750.
Koh, K., J. Wang, J. Yuan, S. Hiew, H. Cheng, B. Gabryelczyk, and A. Miserez (2022). Squid Suckerin–Spider Silk Fusion Protein Hydrogel for Delivery of Mesenchymal Stem Cell Secretome to Chronic Wounds. Advanced Healthcare Materials, 12(1); 220190.
Koob, T., R. Rennert, N. Zabek, M. Massee, J. Lim, J. Temenoff, and G. Gurtner (2013). Biological Properties of Dehydrated Human Amnion/Chorion Composite Graft: Implications for Chronic Wound Healing. International Wound Journal, 10(5); 493–500.
Kraskiewicz, H., P. Hinc, A. Krawczenko, A. Bielawska-Pohl, M. Paprocka, D. Witkowska, I. L. Mohd Isa, A. Pandit, and A. Klimczak (2021). HATMSC Secreted Factors in the Hydrogel as a Potential Treatment for Chronic Wounds In Vitro Study. International Journal of Molecular Sciences, 22(22); 12241.
Krisnayanti, N. P. E., S. Mariya, I. Indriawati, H. Dayana, B. F. D. Zaelani, R. R. Tjandrawinata, and H. S. Darusman (2024). Myristicin Inhibit Invasion and Migration of Melanoma Cells through Suppression of MMP2 and MMP9 Gene Expression. Science and Technology Indonesia, 9(4); 884–892.
Kuncorojakti, S., A. Z. A. Pratama, C. A. Antujala, C. T. B. Harijanto, R. K. Arsy, P. A. Kurniawan, Y. Tjahjono, L. Hendriati, T. Widodo, A. Aswin, D. Diyantoro, A. Y. Wijaya, W. Rodprasert, and H. Susilowati (2024). Acceleration of Wound Healing Using Adipose Mesenchymal Stem Cell Secretome Hydrogel on Partial-Thickness Cutaneous Thermal Burn Wounds: An In Vivo Study in Rats. Veterinary World, 17(7); 1545–1554.
Kwon, J. (2023). Mesenchymal Stem Cell-Derived Secretomes Enriched Alginate/Extracellular Matrix Hydrogel Patch Accelerates Skin Wound Healing. Biomaterials Research, 27(1); 107.
Li, Q., D. Wang, Z. Jiang, R. Li, T. Xue, C. Lin, and B. Sun (2022). Advances of Hydrogel Combined with Stem Cells in Promoting Chronic Wound Healing. Frontiers in Chemistry, 10; 1038839.
Ma, H., P. Lam, W. Siu, C. Tong, K. Lo, C. Koon, and P. Leung (2021). Adipose Tissue-Derived Mesenchymal Stem Cells (ADMSCs) and ADMSC-Derived Secretome Expedited Wound Healing in a Rodent Model – A Preliminary Study. Clinical Cosmetic and Investigational Dermatology, 14; 753–764.
Monfared, G. S., P. Ertl, and M. Rothbauer (2020). An On-Chip Wound Healing Assay Fabricated by Xurography for Evaluation of Dermal Fibroblast Cell Migration and Wound Closure. Scientific Reports, 10; 16192.
Monika, P., M. N. Chandraprabha, A. Rangarajan, P. V. Waiker, and M. K. N. Chidambara (2022). Challenges in Healing Wound: Role of Complementary and Alternative Medicine. Frontiers in Nutrition, 20(8); 791899.
Natallya, F., N. Herwanto, C. Prakoeswa, D. Indramaya, and F. Rantam (2019). Effective Healing of Leprosy Chronic Plantar Ulcers by Application of Human Amniotic Membrane Stem Cell Secretome Gel. Indian Journal of Dermatology, 64(3); 250.
Noh, K., X. Liu, Z. Zhong, C. Yang, Y. Kim, G. Lee, and K. Kim (2018). Leukocyte-Poor Platelet-Rich Plasma-Derived Growth Factors Enhance Human Fibroblast Proliferation in Vitro. Clinics in Orthopedic Surgery, 10(2); 240.
Nuraini, S., S. Saadah, and S. Rismawati (2019). The Effect of Breastmilk Topical on Perineal Wound Healing on 1–7 Days Postpartum Mother. Midwifery and Nursing Research, 1(2); 68.
Qu, F., F. Guilak, and R. L. Mauck (2019). Cell Migration: Implications for Repair and Regeneration in Joint Disease. Nature Reviews Rheumatology, 15(3); 167–179.
Rozirwan, A., Siswanto, N. N. Khotimah, R. Y. Nugroho, W. A. E. Putri, and R. Apri (2024). Anti-Inflammatory Activity and Phytochemical Profile from the Leaves of the Mangrove Sonneratia Caseolaris (L.) Engl. for Future Drug Discovery. Science and Technology Indonesia, 9(2); 502–516.
Saheli, M., M. Bayat, R. Ganji, F. Hendudari, R. Kheirjou, M. Pakzad, B. Najar, and A. Piryaei (2020). Human Mesenchymal Stem Cells-Conditioned Medium Improves Diabetic Wound Healing Mainly Through Modulating Fibroblast Behaviors. Archives of Dermatological Research, 312(5); 325–336.
Sarfraz, M., R. Iqbal, K. U. Khan, and M. U. Minhas (2022). Carbopol Based Hydrogels for Itopride Hydrochloride Delivery; Synthesis, Characterization and Comparative Assessment with Various Monomers. Journal of Functional Biomaterials, 13(4); 295.
Simader, E., D. Traxler, M. Kasiri, H. Hofbauer, M. Wolzt, C. Glogner, and H. Ankersmit (2017). Safety and Tolerability of Topically Administered Autologous, Apoptotic PBMC Secretome (Aposec) in Dermal Wounds: A Randomized Phase 1 Trial (MARSYAS I). Scientific Reports, 7(1).
Suhail, M., J. Y. Liu, M. C. Hung, I. H. Chiu, M. U. Minhas, and P. C. Wu (2022). Preparation, In Vitro Characterization, and Cytotoxicity Evaluation of Polymeric pH-Responsive Hydrogels for Controlled Drug Release. Pharmaceutics, 14(9); 1864.
Sutjiatmo, A. B., W. Widowati, I. Sumiati, T. Priestu, S. Arumwardana, H. S. W. Kusuma, and A. M. Azizah (2021). Antioxidant and Anticancer Potential of Raja Bulu Banana Peel and Heart (Musa Acuminata Colla (AAB Group)) Ethanol Extracts in MCF-7 Cell Lines. Majalah Obat Tradisional, 26(1); 49–58.
Tan, S., P. Aisyah, Y. Firmansyah, N. Nathasia, E. Budi, and S. Hendrawan (2023). Effectiveness of Secretome from Human Umbilical Cord Mesenchymal Stem Cells in Gel (10% SM-hUCMSC Gel) for Chronic Wounds (Diabetic and Trophic Ulcer) – Phase 2 Clinical Trial. Journal of Multidisciplinary Healthcare, 16; 1763–1777.
Wei, Y., J. Li, Y. Huang, X. Lei, L. Zhang, M. Yin, and J. Wu (2022). The Clinical Effectiveness and Safety of Using Epidermal Growth Factor, Fibroblast Growth Factor and Granulocyte-Macrophage Colony Stimulating Factor as Therapeutics in Acute Skin Wound Healing: A Systematic Review and Meta-Analysis. Burns & Trauma, 10; tkac002.
Widowati, W., A. Faried, R. F. Guannegara, F. Raharrdja, F. H. Zahirof, F. A. Sutendi, F. S. Nindya, K. Azis, and R. K. Ekajaya (2024). The Potential of Human Wharton’s Jelly Mesenchymal Stem Cells Secretome-Based Topical Gel for Therapeutic Application. Avicenna Journal of Medical Biotechnology, 16(4); 233–243.
Yamakawa, S. and K. Hayashida (2019). Advances in Surgical Applications of Growth Factors for Wound Healing. Burns & Trauma, 7; s41038–019–0148–1.
Yu, J., S. Choi, J. Um, and K. Park (2017). Reduced Expression of YAP in Dermal Fibroblasts Is Associated with Impaired Wound Healing in Type 2 Diabetic Mice. Tissue Engineering and Regenerative Medicine, 14(1); 49–55.
Zhang, H., W. Li, S. Tang, Y. Chen, L. Lan, S. Li, and G. Jiang (2023). A Boron-Based Probe Driven Theranostic Hydrogel Dressing for Visual Monitoring and Matching Chronic Wound Healing. Advanced Functional Materials, 33(51); 2305580.
Zulharini, M., I. R. Sutejo, H. Fadliyah, and R. I. Jenie (2018). Methanolic Extract of Red Betel Leaves (Piper crocatum Ruiz & Pav) Perform Cytotoxic Effect and Antimigration Activity Toward Metastatic Breast Cancer. Indonesian Journal of Cancer Chemoprevention, 8(3); 94–100.
Authors
Widowati, W., Rahmat, D., Faried, A., Nainggolan, I. M. ., Priyandoko, D., Wargasetia, T. L. ., Sugiaman, V. K. ., Triharsiwi, D. N., Qlintang, S. ., Murti, H., Azis, R., & Jeffrey, J. (2025). Potential of Secretome Hydrogel for Wound Healing in LPS- and Scratch-Induced BJ Cells as an Inflammation Model. Science and Technology Indonesia, 10(4), 1242–1254. https://doi.org/10.26554/sti.2025.10.4.1242-1254
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