Bioengineering • Approval

Revolution in Living Skin Materials by Japan (JACE)

Published • Nov 2007 • 6 min read

JACE marked Japan's first approval of a regenerative medical product. This article looks at why it mattered — not as a headline, but as a regulatory and quality inflection point.

JACE was the inflection point for regulatory approval for medical devices in Japan. Japan approved Japan Tissue Engineering Co., Ltd. (J-TEC) for JACE, an autologous cultured epidermis for severe burns in October 2007. This was Japan's first regenerative medical product, turning laboratory cultured skin into an actual product. This was the starting point of how a living tissue was registered as medical device in the healthcare system.

Based on the documentation, PMDA (Pharmaceuticals and Medical Devices Agency) classified JACE as other surgical/orthopedic materials (autologous cultured epidermis) with product name JACE. Technically speaking, JACE is a thin, multi-layered sheet of the patient's own keratinocytes, cultivated using Green's technique: Keratinocytes isolated from a small skin biopsy are expanded on a feeder layer of irradiated 3T3-J2 mouse cells.

The sequence in clinical application is:
  • Extensive deep burns to the patient.
  • Allografts or artifical dermal substitutes are used to reconstruct dermis by surgeons.
  • JACE sheets are applied to close the wound by engraftment and epithelialization as soon as sermal layer is available.


JACE was approved strictly as indicated for use in patients with serious, extensive burns when sufficient donor sites for autologous skin grafts are not available and the total area of deep dermal and full-thickness burns is 30% or more of the total body surface area.

JACE is not a cosmetic patch for small wounds, but a last line option in patients who would otherwise have no viable skin to graft and have a very high risk of death. However, the sad fact is that the pivotal trail that underpinned approval enrolled only two-patient in an open-label, multi-center study. This was even considered as a weak evidence, but it did force the real question: how much evidence is required when the alternative is no skin, no survival?

JACE matters because it proves that living tissues can be industrialized without killing the medical logic behind them.

Due to the tiny clinical trials of two cases, heavy conditions were imposed:
  • post-marketing clinical studies
  • exhaustive use-result surveys in all patients
  • strick restrictions on where and by whom JACE could be used.
  • Approval was granted as a very special case as the unmet need was extreme and the value was required to be proved in the real world consistently.

Key milestones for JACE:
  • 2004 - Application for JACE submitted to PMDA.
  • Aug 2007 - PMDA review completed (special case, two patients).
  • Oct 2007 - Goverment approval was provided to J-TEC to culture and sell autologous cultured epidermis JACE for serious burns.
  • Closer observation shall be observed for future upgrades.


If biology is striped away, JACE is essentially a bio-engineered material that plugs into an existing surgical workflow. JACE can be understood as a four-layer system:

  1. Biological layer: Patient-derived keratinocytes arranged in multiple layers, capable of engraftment and barrier formation.
  2. Device layer: The sheet is mounted on a carrier, packaged, and shipped like a specialized dressing. It has a brand name and a generic category (“other surgical/orthopedic materials”).
  3. Clinical protocol layer: It can only be used in severe burns >30% TBSA when there is insufficient donor skin; it must be applied in centers with the right surgical and ICU capacity.
  4. Finance/regulation layer: It is reimbursed under NHI only when used in certified facilities, with detailed case documentation and participation in post-marketing surveillance.

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