* Tissue Engineering Strategies to Improve Osteogenesis in the Juvenile Swine Alveolar Cleft Model.

Montserrat Caballero,John A Van Aalst,Sajjad Soleimani,Zhengyuan Shan,Donna C Jones

doi:10.1089/ten.tec.2017.0148

Montserrat Caballero, John A Van Aalst + Show 3 more

Open Access

https://doi.org/10.1089/ten.tec.2017.0148

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Abstract

Alveolar (gumline) clefts are the most common congenital bone defect in humans, affecting 1 in 700 live births. Treatment to repair these bony defects relies on autologous, cancellous bone transfer from the iliac crest. This harvest requires a second surgical site with increased surgical time associated with potential complications, while providing only limited cancellous bone. Improvements in treatment protocols that avoid these limitations would be beneficial to patients with clefts and other craniofacial bone defects. There have been steady advances in tissue-engineered (TE) solutions for long-bone defects and adult patients, but advances for the pediatric craniofacial skeleton have been slower to emerge. This study utilizes a previously established juvenile swine model with a surgically created, critical size alveolar defect to test the efficacy of umbilical cord (UC) mesenchymal stem cells (MSCs) treatments on nano-microfiber scaffolds. At 1 month after implanting our TE construct, mineralized tissue in the surgical gap was quantified through computed tomography (CT), and histology, and excised tissue was subjected to mechanical testing. Both undifferentiated and predifferentiated (toward an osteogenic lineage) UC MSCs generated bone within the cleft on a scale comparable to iliac crest cancellous bone, as evidenced by histology and CT scans. All of the pigs treated with scaffold/stem cell combinations had mineralized tissue within the defect, although without filling the entire defect. Several of the experimental animals exhibited poor and/or asymmetric maxillary growth 1 month after the initial surgery, especially if the surgical defect was located on the smaller side of an already asymmetric pig. Our results demonstrate that tissue engineering approaches using UC MSCs are a promising alternative for repair of the alveolar cleft. Data in the pig model demonstrate that implanted scaffolds are at least as good as the current gold standard treatment based on harvesting cancellous bone from the iliac crest, regardless of whether the cells seeded on the scaffold are precommitted to an osteogenic fate.

Highlights

For critical size bone defects of the craniofacial skeleton in pediatric patients, tissue-engineered (TE) solutions have been slow to develop for a complex set of reasons, including a higher standard for safety and efficacy in children and the need to accommodate growth
Cleft lip and palate are the most common congenital bone defects in humans (1/700 live births).[1,2]. These defects were corrected surgically at 1 year of age with bone harvested from multiple locations including rib, tibia, and calvarium[3]; as these patients grew, it became increasingly apparent that they developed growth restriction of the treated maxilla, which did not keep pace with growth of the remaining craniofacial skeleton
The current gold standard for treatment of the alveolar cleft associated with cleft lip and palate, involves harvest of cancellous bone from the iliac crest, and is generally performed between 7 and 10 years of age

Summary

Introduction

For critical size bone defects of the craniofacial skeleton in pediatric patients, tissue-engineered (TE) solutions have been slow to develop for a complex set of reasons, including a higher standard for safety and efficacy in children and the need to accommodate growth. Cleft lip (including a defect of the alveolus/gumline) and palate (defect in the midline of the maxilla) are the most common congenital bone defects in humans (1/700 live births).[1,2] These defects were corrected surgically at 1 year of age with bone harvested from multiple locations including rib, tibia, and calvarium[3]; as these patients grew, it became increasingly apparent that they developed growth restriction of the treated maxilla, which did not keep pace with growth of the remaining craniofacial skeleton. This growth restriction resulted in smaller bones, often associated with asymmetric craniofacial shape, resulting in functional impairments, such as breathing, feeding, and malocclusion.[4,5,6,7,8]

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