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Preclinical Development of Bioengineered Allografts Derived from Decellularized Human Diaphragm
Silvia Barbon1,2,3, Elena Stocco1,2,3, Martina Contran1
1Section of Human Anatomy, Department of Neuroscience, University of Padova, 35121 Padova, Italy.
Biomedicines
|April 23, 2022
Summary
This study explores decellularized human diaphragm scaffolds for volumetric muscle loss (VML) repair. These biocompatible grafts show promise for regenerative medicine, minimizing immune response and promoting tissue integration.
Area of Science:
- Biomaterials Science
- Regenerative Medicine
- Tissue Engineering
Background:
- Volumetric muscle loss (VML) presents significant reconstructive challenges due to functional and aesthetic deficits.
- Current surgical treatments for VML are suboptimal, necessitating advanced regenerative therapies.
- Bioengineered scaffolds from decellularized muscle offer a promising avenue for VML repair.
Purpose of the Study:
- To evaluate the efficacy of decellularized human diaphragm as a scaffold for VML treatment.
- To assess the impact of various detergent-enzymatic protocols on scaffold properties and immunogenicity.
- To determine the biosafety and host tissue integration of these acellular grafts.
Main Methods:
- Human diaphragm tissue underwent decellularization using four distinct detergent-enzymatic protocols (SDS, SDS + Tergitol™, sodium deoxycholate, Tergitol™).
- Scaffold integrity was assessed by quantifying DNA, collagen, elastin, and glycosaminoglycan content.
- Extracellular matrix marker expression (Collagen I, IV, Laminin, HLA-DR) and scaffold biosafety via co-culture with adipose-derived stem cells were evaluated.
- Subcutaneous implantation in Balb/c mice assessed host tissue integration and immune response.
Main Results:
- Decellularization effectively removed cells and DNA while preserving key extracellular matrix components like collagen and glycosaminoglycans.
- Protocols maintained essential matrix markers and eliminated immunogenic HLA-DR expression.
- Decellularized scaffolds demonstrated biosafety, supporting adipose-derived stem cell viability.
- SDS + Tergitol™ treatment showed superior collagen preservation.
- In vivo implantation revealed minimal immune reaction and successful host tissue integration.
Conclusions:
- Decellularized human diaphragm scaffolds are viable for VML regenerative strategies.
- Optimized decellularization protocols yield safe, non-immunogenic scaffolds with preserved structural integrity.
- These scaffolds demonstrate potential for promoting functional muscle tissue regeneration.
