^{Tissue Engineering Strategies to Improve Osteogenesis in the Juvenile Swine Alveolar Cleft Model}

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.

Dipyridamole-loaded 3D-printed bioceramic scaffolds stimulate pediatric bone regeneration in vivo without disruption of craniofacial growth through facial maturity

“…An ideal pediatric bone replacement or regenerative therapeutic agent would be biocompatible, patient specific, bioresorbable, lead to the regeneration of mature, vascularized bone and ultimately restore form and function of the skeleton without impeding facial development 16,18 . Due to these unique considerations, efficacious translation of bone tissue engineering strategies in a pediatric context have been limited and investigation into pediatric skeletal tissue engineering strategies remains in its infancy 20,21 . We seek to evaluate a novel tissue regeneration strategy that may begin to fulfill these criteria for successful translation to a pediatric craniofacial context by investigating both a cleft and calvarial surgical defect model.…”

Use of Human Dental Pulp and Endothelial Cell Seeded Tyrosine-Derived Polycarbonate Scaffolds for Robust in vivo Alveolar Jaw Bone Regeneration

“…Craniomaxillofacial injuries represent up to 26% of all battlefield injuries, as occurred in Operation Iraqi Freedom/Operation Enduring Freedom (Afghanistan) 1 ( Lew et al, 2010 ; U.S. Army Medical Research and Development Command, 2019 ). Craniofacial defects are also a common birth defect (1:700), which poses significant challenges for the health and development of, and reparative therapies for, affected children whose facial bones are actively growing ( Caballero et al, 2017 ). Large CMF boney defects caused by tumor resection, trauma, and birth defects commonly require highly specialized surgical interventions due to the limited regenerative potential of craniofacial bones.…”

Personalized Bone Reconstruction and Regeneration in the Treatment of Craniosynostosis

“…The use of additive manufacturing techniques for a customized replication of the architecture of the skull and bony defects, based on tomographic data, would facilitate the achievement of this ambitious purpose, promoting surgical placement and retention of the engineered scaffold. Therefore, based on such considerations, the application of bone tissue engineering strategies in this specific pediatric context is limited and at an infancy state [202]. Nevertheless, the everlasting efforts of the scientific community have achieved some specific advancements in the field of novel biomaterials and drug delivery systems.…”