Project Details
Description
PROJECT SUMMARY/ABSTRACT
Current approaches in repairing craniomaxillofacial (CMF) defects possess several limitations and the
reconstruction of CMF defects seamlessly is highly challenging, as precise layer-by-layer stacking of multiple
tissue compartments is not trivial. Such compartmentalization necessitates the precision and effective use of
stem cells and differentiation factors, and differentiating stem cells into multiple lineages is crucial in order to
recapitulate the native tissue anatomy. With the advances in three-dimensional (3D) bioprinting, reconstruction
of composite tissues in situ for CMF repair has recently become feasible as 3D bioprinting enables complex
tissue heterogeneity in an anatomically accurate and cosmetically appealing manner. Intraoperative
bioprinting, which can be defined as bioprinting directly into the defect area for repairing injuries in a surgery
setting, is a highly effective process for CMF reconstruction, where the defect information can be rapidly
acquired with minimum manual interventions, enabling accurate personalized reconstructions immediately after
characterization of the defect. In this project, we hypothesize that intraoperatively bioprinted multi-layer
composite tissues loaded with differentiation factors including microRNA(miRNA)-transfected human
progenitor cells and adipose-derived extracellular matrix components (adECM) induce compartmentalization of
soft and hard tissues that recapitulates CMF tissue anatomy on an athymic rat model. In order to test our
hypothesis, Specific Aim I will use intraoperative bone tissue bioprinting to reveal the impact of miR-148b-
transfected human adipose-derived stem cells (ADSCs) at respective dosages on bone tissue regeneration. In
Specific Aim II, we will intraoperatively bioprint multi-layer skin tissues, including adipose and dermis layers, in
order to explore the impact of localized delivery of human ADSCs and adECM components at different
dosages and concentrations on skin tissue regeneration, respectively. Particularly, we will observe if ADSCs
differentiate into adipocytes and also understand the impact of the presence of adipose layer on dermis
regeneration. In Specific Aim III, we will intraoperatively bioprint three-layer composite tissues, including
cranium, adipose and dermis layers, in order to understand the role of a vascularization on soft and hard tissue
regeneration. In addition, we will explore the role of miR-210 in vascularization. In this regard, we have formed
a complementary collaboration that merges essential domain knowledge in bioprinting, regenerative medicine,
CMF surgery, plastic surgery, gene therapy, gene delivery, bone mechanics, and bone and skin biology with
the depth necessary to propel the proposed work towards meaningful advances that would otherwise not be
possible. Successful completion of the proposed work is anticipated to give rise to an advanced bioprinting
technology revealing the complex interactions between stratified layers of engineered tissues in an
immunodeficient rodent model and thereby provide a novel understanding of how localized delivery of
differentiation factors impacts craniomaxillofacial reconstruction.
Status | Active |
---|---|
Effective start/end date | 1/1/20 → 12/31/24 |
Funding
- National Institute of Dental and Craniofacial Research: $498,967.00
- National Institute of Dental and Craniofacial Research: $493,512.00
- National Institute of Dental and Craniofacial Research: $565,387.00
- National Institute of Dental and Craniofacial Research: $558,727.00
- National Institute of Dental and Craniofacial Research: $518,588.00
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