Regenerative Medicine Approaches for the Treatment of Pediatric Physeal Injuries

Abstract

The physis, or growth plate, is a cartilaginous region at the end of children's long bones that serves as the primary center for longitudinal growth and characterizes the immature skeleton. Musculoskeletal injury, including fracture, infection, malignancy, or iatrogenic damage, has risk of physeal damage. Physeal injuries account for 30% of pediatric fractures and may result in impaired bone growth. Once damaged, cartilage tissue within the physis is often replaced by unwanted bony tissue, forming a "bony bar" that can lead to complications such as complete growth arrest, angular or rotational deformities, and altered joint mechanics. Children with a bony bar occupying <50% of the physis usually undergo bony bar resection and insertion of an interpositional material, such as a fat graft, to prevent recurrence and allow the surrounding uninjured physeal tissue to restore longitudinal bone growth. Clinical success for this procedure is <35% and often the bony bar and associated growth impairments return. Children who are not candidates for bony bar resection due to a physeal bar occupying >50% of their physis undergo corrective osteotomy or bone lengthening procedures. These approaches are complex and have variable success rates. As such, there is a critical need for regenerative approaches to not only prevent initial bony bar formation but also regenerate healthy physeal cartilage following injury. This review describes physeal anatomy, mechanisms of physeal injury, and current treatment options with associated limitations. Furthermore, we provide an overview of the current research using cell-based therapies, growth factors, and biomaterials in the different animal models of injury along with strategic directions for modulating intrinsic injury pathways to inhibit bony bar formation and/or promote physeal tissue formation. Pediatric physeal injuries constitute a unique niche within regenerative medicine for which there is a critical need for research to decrease child morbidity related to this injurious process.

Enlightenment of Growth Plate Regeneration Based on Cartilage Repair Theory: A Review

“…Similarly, outcomes are unsatisfactory ( Ladenhauf et al, 2020 ). Unfortunately, clinical efforts will lead to secondary damage or result in the recurrence of bone bridge formation ( Shaw et al, 2018 ). It is critical to identify new approaches to prevent bone bridge formation and to promote tissue regeneration.…”

The Role of Collagen Scaffold and Stromal Vascular Fraction on Healing Process in Growth Plate Injury (SOX9 and Histological Examination)

“…As such, there is a dire need to develop new treatment strategies for growth plate injury that not only prevents bony bridge formation but also leads to regeneration of healthy growth plate cartilage, thus restoring normal bone elongation. Methods under investigation include modulating intrinsic injury pathways to prevent osteogenesis as well as recruiting or adding stem cells for regenerating damaged growth plate [1].…”

Frequency of limb shortening in femoral shaft fractures treated by hip spica casting in children in Tertiary Care Hospital.

“…Due to growing age, there is robust potential in children under five years to remodel the involved bony structures, and fractures closer to the physis may have greater tendency of remodeling than others. 2 In children, fracture potentially stimulate the bone growth and hence, there is risk of limb-length overgrowth. 3 Different options of treatment of pediatric femoral shaft fractures comprised of non surgical like pavlik harness, hip spica casting and surgical including plating, flexible nailing and external fixation etc.…”