Special Collection: Tissue Engineering for Pediatric Applications
Severe birth defects occur in approximately 2-3% of live-born infants and are a leading cause of death in the young. Structural malformations can occur in just about any major organ system and often their causes are unknown. The pediatric population presents a unique set of opportunities to the field of tissue engineering and regenerative medicine (TERM). Infants and young children have significantly greater regenerative capacity than adults which could be leveraged in TERM strategies. Children also arguably stand to benefit the most from TERM. While the lack of growth potential and relatively short life span of synthetic materials may be suitable for adults, it is unacceptable for children. Furthermore, given that there is a particular scarcity of pediatric donor organs, the need for living, functional tissue replacements that can grow with the child is quite evident. There is enormous potential for the TERM community to address the needs of the pediatric population.
This special collection gives a glimpse of the vast array of challenges and opportunities in pediatric TERM. The methods paper by Jiang et al. presents an interesting concept of “perinatal tissue engineering” by deriving induced pluripotent stem cells from the placental chorion, a tissue which is genetically identical to the baby and usually discarded at birth. Benavides et al. show that amniotic fluid derived stem cells, which can be harvested before birth, are capable of generating blood vessel-like networks. In addition, Duan et al. emphasizes the need to consider appropriate cell sources either for implantation or comparison, as pediatric and adult cells can behave quite differently. The papers by Caballero et al., Gutierrez et al., Shakir et al., Santa Maria et al., and Ott et al. highlight the importance of using young animal models to test pediatric TERM strategies. In order for TERM to see widespread clinical translation, it must be cost effective. To this end, work from the labs of Toshiharu Shinoka and Christopher Breuer, who have made some of the most significant advances in pediatric TERM, present a “closed system” approach for engineered vascular grafts as an alternative to the “open” clean room (Kurobe et al.).
Target applications represented in this collection are equally varied, although far from exhaustive. Craniofacial defects present at birth or due to trauma result in significant morbidity in children and are addressed by the work of Caballero et al. and Shakir et al. Heart valves are one of the most desperately needed engineered tissues for children born with congenital heart defects; some interesting findings in cell-based and decellularized scaffold-based approaches are presented by Duan et al. and Gutierrez et al., respectively. Santa Maria et al. show promising results from a growth factor-loaded hydrogel for non-surgical repair of chronic perforation of the tympanic membrane, a major cause of hearing loss in children in developing countries. Finally, Ott et al. demonstrate a functional tissue engineered solution for tracheal stenosis, a life-threatening condition that can be congenital or acquired in children. Many of these challenges, opportunities, and applications could also be extended more broadly to adult disease.
The recent advances in pediatric TERM that have been collected in this special issue are exciting. Nevertheless, there are several major hurdles to success which need to be addressed in future work. Some birth defects are due to genetic mutations that result in impaired cell and tissue function. Gene editing or other creative approaches to overcome inherent defects will likely need to be combined with TERM for autologous cell-based repair and regeneration for these patients. Children with severe structural defects require surgical reconstruction of large portions of tissue or even whole organ transplant. The generation of thick, vascularized grafts that recapitulate the complex structure and function of native tissue remains a major challenge to the field of tissue engineering. Finally, it must be noted that the physiology and pathology of diseases in children is often much different than adults. Therapies that have been developed for adults often fail or cannot be readily adapted to children. Therefore, demonstration of safety is also paramount for pediatric TERM applications, as it is often unknown how children will respond to certain therapies or what the appropriate dose should be. The development of appropriate animal models for pediatric defects and diseases will be necessary for the pre-clinical testing and eventual clinical translation of promising TERM strategies that will improve the survival and quality of life of many children.