Applications of a Mouse Model of Calvarial Healing: Differences in Regenerative Abilities of Juveniles and Adults

Abstract

Young children are capable of healing large calvarial defects, whereas adults lack this endogenous osseous tissue-engineering capacity. Despite the important clinical implications, little is known about the molecular and cell biology underlying this differential ability. Traditionally, guinea pig, rabbit, and rat models have been used to study the orchestration of calvarial healing. To harness the research potential of knockout and transgenic mice, the authors developed a mouse model for calvarial healing. Nonsuture-associated parietal defects 3, 4, and 5 mm in diameter were made in both juvenile (6-day-old, n = 15) and adult (60-day-old, n = 15) mice. Calvariae were harvested after 8 weeks and analyzed radiographically and histologically. Percentage of healing was quantified using Scion Image software analysis of calvarial radiographs. A significant difference in the ability to heal calvarial defects was seen between 6-day-old and 60-day-old mice when 3-, 4-, or 5-mm defects were created. The authors' analysis revealed that juvenile mice healed a significantly greater percentage of their calvarial defects than adult mice (juvenile mean percentage of healing: 3-mm defects, 59 percent; 4-mm defects, 65 percent; 5-mm defects, 44 percent; adult mean percentage of healing: <5 percent in all groups; p < 0.05). All three defect sizes were found to be critical in the adult, whereas significant healing was seen regardless of the size of the defect in juvenile mice. The establishment of this model will facilitate further, detailed evaluation of the molecular biology underlying the different regenerative abilities of juvenile versus adult mice and enhance research into membranous bone induction by making available powerful tools such as knockout and transgenic animals.

Human fetal bone cells associated with ceramic reinforced PLA scaffolds for tissue engineering

“…Thus, the CSD created on the bony vault of the cranium (calvaria) represents a severe test for bone graft substitutes. CSDs in the calvaria have been established for different mammalian species [9][10][11][12][13][14]. Modelling on parietal bone has been applied on rats from different strains and at various ages [10,[15][16][17][18].…”

Repair of critical size defects in the rat cranium using ceramic‐reinforced PLA scaffolds obtained by supercritical gas foaming

“…4 CSDs in the calvaria have been established for different animal species. [4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20] The rat calvarial model offers advantages: the parietal bone is a large plate that facilitates the operation and the analysis (histology, imaging), no implant fixation is required, and the costs are limited in comparison with large animal models. Furthermore, as this experimental approach is widely used, a precise comparison of different grafted materials is possible.…”

Cranial bone defects: current and future strategies

“…Sparing the dura mater is in fact critically important since several studies have shown that the dura is instrumental in bony regeneration of the skull. 1,35,117 As previously noted, humans up to 2 years of age have the capacity to spontaneously heal cranial defects that would be "critical" in an adult human. In 2003, Aalami et al 1 reported similar findings in a mouse model of juvenile and adult cranial defect healing: in the juvenile mice (6 days old) a significantly greater portion of critical-size calvarial defects was healed than in the adults (60 days old).…”

“…Additionally, sophisticated molecular and cellular biology analytical tools are readily available and yield highly reproducible results. 1 In the mouse, a critical-size cranial defect is defined as a bony deficit greater than or equal to 5 mm. 63,67,80 Such a defect, if left untreated, will not heal in the life of an animal.…”