Biological Skin Graft With Keratinocyte-stem Cell Co-cultre for Burn Patients

Substitute Graft for Burns Using Biological Graft Seeded With Autologous Keratinocyte Co-cultured With Stem Cells

The goal of this clinical trial is to test whether artificial skin graft can substitute autologous skin graft in current burn treatment. The main question it aims to answer is:

• Can artificial skin graft result in better wound healing compared to the current burn treatment; autologous skin graft?

You will:

• Undergo debridement surgery
• Receive artificial skin graft as an alternative to autologous skin graft
• Undergo biopsy procedure of burn area

If there is a comparison group: Researchers will compare autologous skin graft group to see the wound healing process

Study Overview

• Status: Recruiting
• Conditions: Burn Degree Second; Burn Degree Third
• Intervention / Treatment: Procedure: Split-thickness skin graft; Biological: Artificial skin graft; Biological: Artificial skin graft co-culture

Detailed Description

Burn caused by working accidents occurs mostly in the male population of productive age (68.68%). Up to this date, the only treatment for grade 2B-3 burns patients in Indonesia is skin transplantation taken from their own body (autologous skin graft). This treatment has several drawbacks in which repeated surgery is sometimes necessary, the source of skin in patients with wide area of burn is limited, and patients that are in the elder age and have comorbidities have high mortality risk.

In order to find an alternative for autologous skin graft therapy, a combination of tissue engineering and stem cell therapy is used to invent an artificial skin graft. The present study attempts to evaluate the efficacy of artificial skin graft seeded with autologous keratinocyte and stem cells towards wound healing in burn patients. The artificial graft used in this study is amnion bilayer; a graft that was decellularized to remove donor's cells and then layered to form into 3-D.

To evaluate the efficacy, biopsies are taken from the burn area of patients to evaluate the histoarchitecture of patients' tissue by histological staining (H&E and Movat's pentachrome, IHC collagen I, collagen III, vWF, and alpha-SMA) and measure the relative gene expression by qPCR. For clinical data, burn area calculation using Rule of 9 method and thermography measurement using FLIRONE. Furthermore, systemic evaluation of patients are done by monitoring the procalcitonin, lactate, mean arterial pressure, gradation of wound, and sensory of burn area. The evaluation and measurement mentioned above are then compared to patients treated with the current available therapy; autologous skin graft. The artificial skin graft is hoped to result in equal, if not better, wound healing in burn patients compared to autologous skin graft. The investigators hope that artificial skin graft can be an option, other than autologous skin graft, in treating burn patients in the future.

• Study Type: Interventional
• Enrollment (Anticipated): 20
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Indonesia
  • DKI Jakarta
    • Jakarta Pusat, DKI Jakarta, Indonesia, 10430
      • Recruiting
      • RSUPN Cipto Mangunkusumo
      • Contact: Aditya Wardhana, MD; Phone Number: +6287880021350; Email: aditya_wrdn@yahoo.com
      • Contact: Normalina Sandora, PhD; Phone Number: +6281298963425; Email: normalina.sandora@gmail.com

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aged 18 - 55
• Area of burn <50%
• Acute phase burn (<120 hrs)
• Have not undergo any surgery for burn treatment

Exclusion Criteria:

• Immunocompromised
• Have comorbidities

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Sham Comparator: STSG (Split-Thickness Skin Graft); Patients treated with the standard treatment; autologous skin graft	Procedure: Split-thickness skin graft; Transplantation of autologous skin to burn area
Experimental: Amnion Bilayer Only; Patients treated with artificial graft only	Biological: Artificial skin graft; Decellularized amnion membrane formed into 3-D matrix
Experimental: Amnion Bilayer seeded with co-culture; Patients treated with artificial graft seeded with autologous keratinocyte co-cultured with amnion epithelial stem cells	Biological: Artificial skin graft co-culture; Decellularized amnion membrane formed into 3-D matrix seeded with autologous keratinocyte co-cultured with amnion epithelial stem cells

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Burn thickness	Thickness of burn evaluation using Rule of 9	Day of surgery
Burn thickness	Thickness of burn evaluation using Rule of 9	Day 7 after surgery
Burn thickness	Thickness of burn evaluation using Rule of 9	Day 14 after surgery
Burn thermography	Thermography evaluation using FLIRONE	Day of surgery
Burn thermography	Thermography evaluation using FLIRONE	Day 7 after surgery
Burn thermography	Thermography evaluation using FLIRONE	Day 14 after surgery
Systemic clinical evaluation	Mean arterial pressure measurement	Day of surgery
Systemic clinical evaluation	Mean arterial pressure measurement	Day 7 after surgery
Systemic clinical evaluation	Mean arterial pressure measurement	Day 14 after surgery
Systemic clinical evaluation	lactate measurement	Day of surgery
Systemic clinical evaluation	lactate measurement	Day 7 after surgery
Systemic clinical evaluation	lactate measurement	Day 14 after surgery
Systemic clinical evaluation	procalcitonin measurement	Day of surgery
Systemic clinical evaluation	procalcitonin measurement	Day 7 after surgery
Systemic clinical evaluation	procalcitonin measurement	Day 14 after surgery
Systemic clinical evaluation	urine excretion rate measurement	Day of surgery
Systemic clinical evaluation	urine excretion rate measurement	Day 7 after surgery
Systemic clinical evaluation	urine excretion rate measurement	Day 14 after surgery
Histoarchitecture evaluation	Haematoxylin & Eosin staining	Day of surgery
Histoarchitecture evaluation	Haematoxylin & Eosin staining	Day 14 after surgery
Histoarchitecture evaluation	Movat's Pentachrome staining	Day of surgery
Histoarchitecture evaluation	Movat's Pentachrome staining	Day 14 after surgery
Immunohistochemistry	collagen-1 labelling	Day of surgery
Immunohistochemistry	collagen-1 labelling	Day 14 after surgery
Immunohistochemistry	collagen-3 labelling	Day of surgery
Immunohistochemistry	collagen-3 labelling	Day 14 after surgery
Immunohistochemistry	von Willebrand labelling	Day of surgery
Immunohistochemistry	von Willebrand labelling	Day 14 after surgery
Immunohistochemistry	alpha-Smooth Muscle Actin labelling	Day of surgery
Immunohistochemistry	alpha-Smooth Muscle Actin labelling	Day 14 after surgery
Wound healing relative gene expression	TGFB1	Day of surgery
Wound healing relative gene expression	TGFB1	Day 14 after surgery
Wound healing relative gene expression	TGFB3	Day of surgery
Wound healing relative gene expression	TGFB3	Day 14 after surgery
Wound healing relative gene expression	Wnt4	Day of surgery
Wound healing relative gene expression	Wnt4	Day 14 after surgery
Wound healing relative gene expression	CTNNB1	Day of surgery
Wound healing relative gene expression	CTNNB1	Day 14 after surgery
Wound healing relative gene expression	MMP2	Day of surgery
Wound healing relative gene expression	MMP2	Day 14 after surgery
Wound healing relative gene expression	MMP9	Day of surgery
Wound healing relative gene expression	MMP9	Day 14 after surgery

Collaborators and Investigators

• Sponsor: Indonesia University

Study record dates

Study Major Dates

• Study Start (Actual): September 6, 2022
• Primary Completion (Anticipated): December 31, 2023
• Study Completion (Anticipated): December 31, 2024

Study Registration Dates

• First Submitted: November 29, 2022
• First Submitted That Met QC Criteria: December 8, 2022
• First Posted (Actual): December 15, 2022

Study Record Updates

• Last Update Posted (Actual): December 15, 2022
• Last Update Submitted That Met QC Criteria: December 8, 2022
• Last Verified: December 1, 2022

More Information

Terms related to this study

• Keywords: burn; artificial skin graft; keratinocyte; amnion epithelial stem cells
• Additional Relevant MeSH Terms: Wounds and Injuries; Burns
• Other Study ID Numbers: KET-866/ETIK/2021

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No