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ORIGINAL RESEARCH
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Three-dimensional cellularized matrix supplemented with secretome enhances tissue regeneration in an incisional hernia repair model

Siufui Hendrawan1,2* ,  Olivia Marcelina1 ,  Astheria Eryani3 ,  Erwin Siahaan4 ,  Hans U. Baer1,5,6
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1 Tarumanagara Human Cell Technology Laboratory, Faculty of Medicine, Tarumanagara University, Jakarta, Indonesia
2 Department of Biochemistry and Molecular Biology, Faculty of Medicine, Tarumanagara University, Jakarta, Indonesia
3 Department of Histology, Faculty of Military Medicine Defense University, Bogor, West Java, Indonesia
4 Department of Mechanical Engineering, Faculty of Engineering, Tarumanagara University, Jakarta, Indonesia
5 Baermed Tissue Engineering Limited, Freienbach, Switzerland
6 Department of Visceral and Transplantation Surgery, Faculty of Medicine, University of Bern, Bern, Switzerland
BMT, 00041 https://doi.org/10.12336/bmt.25.00041
Submitted: 21 May 2025 | Revised: 5 August 2025 | Accepted: 6 August 2025 | Published: 4 September 2025
Copyright © 2025 by the Author(s). This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution–NonCommercial–ShareAlike 4.0 License.
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Abstract

Present standard treatment for incisional hernia (IH) focuses on wound closure by providing mechanical reinforcement to the affected tissue, generally through the implantation of synthetic polypropylene (PP) mesh. However, PP mesh primarily functions to hold organs in place and does not actively stimulate intrinsic tissue regeneration. Meanwhile, in the aging population and in individuals with pre-existing complications, impaired wound healing and reduced elasticity increase the risk of hernia recurrence. In this study, we developed a three-dimensional cellularized implant with secretome (Sec) supplementation, aiming to promote tissue regeneration and the formation of a more mechanically robust scar in IH repair. The cellularized matrix (Cell/Matrix) was produced by seeding fibroblasts onto a three-dimensional collagen-coated poly-L-lactic acid matrix. Supplementation with Sec derived from human umbilical cord mesenchymal stem cells was performed to produce the Cell/Matrix+Sec implant. Implantation was performed in the sublay position (between muscle and peritoneal membrane), beneath an incisional cut at the midline abdomen of Wistar rats to mimic IH repair. Rats with no implant (Sham) served as the control group, while others received PP mesh (Mesh), an acellularized matrix (Matrix), Cell/Matrix, and Cell/Matrix+Sec implants. At 2 months post-implantation, abdominal tissue samples extracted from the Cell/Matrix+Sec implant group exhibited the greatest biomechanical strength, accompanied by a higher collagen type I/III ratio, neovascularization count, α-smooth muscle actin-positive vessels, and formation of neuron bundles. Meanwhile, Sham and Mesh groups displayed the lowest values in all parameters, respectively. Despite having lower mechanical strength compared with PP mesh, implantation of the cellularized matrix resulted in better muscle tissue integrity and maturation. Hence, these findings highlight the potential of Cell/Matrix+Sec as a novel adjuvant implant to complement the present standard approach to hernia repair, which lacks regenerative capacities.

Keywords
Abdominal tensile strength
Collagen ratio
Incisional hernia
Poly-L-lactic acid cellularized matrix
Secretome
Human umbilical cord-derived mesenchymal stem cells
Funding
This study was funded by the Institute of Research and Community Service of Tarumanagara University (grant numbers: 0437-Int-KLPPM/ UNTAR/V/2024; 070-SPK-PENREG-KLPPM/UNTAR/IV/2024) and supported by Baermed Tissue Engineering Ltd., Freienbach, Switzerland.
Conflict of interest
HUB has an interest in acquiring intellectual properties in tissue engineering. Other authors declare no potential conflict of interest.
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