The use of human hypertrophic chondrocytes‐derived extracellular matrix for the treatment of critical‐size calvarial defects

Abstract

To evaluate the effect of immortalized hypertrophic chondrocytes extracellular matrix (HCM) with or without the use of guided bone regeneration (GBR) on the healing of critical-size calvarial defects. In 42 rats, 5 mm critical-size calvarial defects were surgically created. The animals were randomly allocated to six groups of seven rats each: Group A1: one defect was left untreated (control), while the contralateral defect was covered by a double non-resorbable membrane (GBR). Group B1: one defect was filled with calcium phosphate cement (CP), while the contralateral defect was treated with GBR and CP. Group C1: one defect was filled with a mixture of CP and HCM, while the contralateral defect was treated with GBR and CP+HCM. The healing period for all three groups was 30 days. The remaining three groups were treated in a similar manner but the healing period was 60 days. Five animals from each group were evaluated by maceration and two animals were analysed histologically. At 30 days, all the control-treated defects did not present complete closure. When GBR was applied alone or combined with CP, 3/5 and 5/5 defects, respectively, presented complete closure. At 60 days, one defect from the control group presented complete closure. All the defects treated with GBR alone presented complete closure, whereas the combined use of GBR with CP or CP+HCM resulted in 4/5 and 3/5 defects with complete closure, respectively. The only treatment modality that did not present any specimen with defect closure at both 30 and 60 days was the combination of CP+HCM. The histological analysis indicated that when GBR was not used alone, the healing consisted of an amorphous acellular structure and loose granulation tissue, which, even though clinically resembled hard tissue, did not demonstrate the histological characteristics of bone. The predictability of bone formation in critical-size defects depends mainly on the presence or absence of barrier membranes. The combined use of GBR with calcium phosphate alone or in combination with immortalized human HCM did not enhance the potential for osseous healing provided by the GBR procedure.