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Strategies and challenges in developing pre-vascularized three-dimensional skin substitutes using layer-by-layer cell
Yasuyuki Tsunoi1, Hiromi Miyazaki2
1Division of Bioinformation and Therapeutic Systems, National Defense Medical College Research Institute, 3-2 Namiki, Tokorozawa, Saitama, 359-8513, Japan.
Regenerative Therapy
|May 1, 2026
Summary
This study explores advanced tissue engineering for vascularized 3D skin substitutes. A novel layer-by-layer (LbL) method combined with photobiomodulation (PBM) shows promise for treating extensive skin injuries.
Area of Science:
- Tissue Engineering
- Regenerative Medicine
- Biomaterials Science
Background:
- Autologous skin grafts are limited for extensive injuries.
- Conventional artificial skin lacks vascularization, leading to complications.
- Developing vascularized 3D skin substitutes is crucial for wound healing.
Purpose of the Study:
- To review progress in tissue-engineered 3D skin models.
- To highlight the layer-by-layer (LbL) method for fabricating 3D skin.
- To introduce photobiomodulation (PBM) for enhancing LbL-3D skin cultivation.
Main Methods:
- Review of tissue engineering techniques for 3D skin.
- Detailed explanation of the layer-by-layer (LbL) method for extracellular matrix film formation.
- Application of photobiomodulation (PBM) to LbL-3D skin constructs during cultivation.
Main Results:
- The LbL method promotes cell self-assembly and ultrathin film formation.
- Photobiomodulation (PBM) was successfully applied to LbL-3D skin.
- Transplantation of LbL-3D skin onto a mouse wound model was performed.
Conclusions:
- Advanced tissue engineering offers solutions for vascularized skin substitutes.
- The LbL method combined with PBM presents a novel approach for skin regeneration.
- Further research is needed to optimize this technique for clinical application in intractable wounds.

