Following a decompressive craniectomy, the autologous bone flap is generally considered the reconstructive material of choice in pediatric patients. Replacement of the original bone flap takes advantage of its natural biocompatibility and the associated low risk of rejection, as well as the potential to reintegrate with the adjacent bone and subsequently grow with the patient. However, despite these advantages and unlike adult patients, the replaced calvarial bone is more likely to undergo delayed bone resorption in pediatric patients, ultimately requiring revision surgery. In this review, we describe the materials that are currently available for pediatric cranioplasty, the advantages and disadvantages of autologous calvarial replacement, the incidence and classification of bone resorption, and the clinical risk factors for bone flap resorption that have been identified to date.

Cell therapy is emerging as an effective treatment strategy for many diseases. Here we describe a novel approach to bone tissue repair that combines hydrogel‐based cell therapy with low intensity pulsed ultrasound (LIPUS), an FDA approved treatment for fracture repair. Bone marrow‐derived stromal cells (BMSCs) have been encapsulated in type I collagen hydrogels and mechanically stimulated using LIPUS‐derived acoustic radiation force (ARF). We observed the expression and upward trend of load‐sensitive, osteoblast‐specific markers and determined that the extent of cell response is dependent on an optimal combination of both hydrogel stiffness and ARF intensity. Specifically, cells encapsulated in hydrogels of optimal stiffness respond at the onset of ultrasound by upregulating early bone‐sensitive markers such as calcium, cyclooxygenase‐2, and prostaglandin E2, and later by supporting mineralized tissue formation after 21 days of culture. In vivo evaluation of a critical size calvarial defect in NOD scid gamma (NSG) mice indicated that the implantation of BMSC‐laden hydrogels of optimal stiffness improved healing of calvarial defects after daily administration of ARF over 4 weeks. Collectively, these findings validate the efficacy of our system of localized cell delivery for treating bone defects where undifferentiated BMSCs are induced to the osteoblastic lineage. Further, in vivo healing may be enhanced via non‐invasive transdermal mechanical stimulation of implanted cells using ARF.

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