A 1-Year Study of Osteoinduction in Hydroxyapatite-Derived Biomaterials in an Adult Sheep Model: Part I

Abstract

The study presented here investigated hydroxyapatite biomaterials implanted in soft-tissue sites in adult sheep to determine whether these materials are osteoinductive and whether the rate of osteoinduction can be increased by manipulating the composition and porosity of the implants. For the study, 16.8-mm x 5-mm discs were prepared from mixtures of hydroxyapatite and beta-tricalcium phosphate. Five mixtures of hydroxyapatite-ceramic and hydroxyapatite-cement paste forms were studied: 100 percent hydroxyapatite-ceramic (Interpore), 60 percent hydroxyapatite-ceramic, 100 percent hydroxyapatite-cement paste, 60 percent hydroxyapatite-cement paste, and 20 percent hydroxyapatite-cement paste. Biomaterials were implanted in subcutaneous and intramuscular soft-tissue pockets in 10 adult sheep. Cranial bone grafts of equal dimension were implanted as controls. One year after implantation, the volume of all biomaterials and bone grafts was determined from a computed tomographic scan, and porosity and bone formation were determined using backscatter electron microscopy. Cranial bone and the 20 percent hydroxyapatite-cement paste implants demonstrated significant volume reduction in all sites after 1 year (p < 0.001). No significant difference in volume of the remaining four biomaterials was found. There was no significant change in pore size in the ceramic implants (range, 200 to 300 micro) and in the cement-paste implants containing 60 percent hydroxyapatite or more (range, 3 to 5 nm). Pore size in the cement-paste implants containing 20 percent hydroxyapatite increased significantly with resorption of the tricalcium-phosphate component, reaching a maximum of 200 to 300 micro in the periphery, where the greatest tricalcium-phosphate resorption had occurred. Both ceramic biomaterials demonstrated lamellar bone deposition within well-formed haversian systems through the entire depth of the implants, ranging from a mean of 6.6 percent to 11.7 percent. There was minimal bone formation in the cement-paste implants containing 60 percent hydroxyapatite or more. In contrast, cement-paste implants containing 20 percent hydroxyapatite demonstrated up to 10 percent bone replacement, which was greatest in the periphery of the implants where the greatest tricalcium-phosphate resorption had occurred. This study confirms the occurrence of true osteoinduction within hydroxyapatite-derived biomaterials, when examined using backscatter techniques. In this study, the rate of osteoinduction was greatest when a porous architecture was maintained, which was best achieved in ceramic rather than cement-paste forms of hydroxyapatite. Porosity and resultant bone formation in cement-paste implants can be improved by combining hydroxyapatite with a rapidly resorbing component, such as tricalcium phosphate.

Relevance of Osteoinductive Biomaterials in Critical‐Sized Orthotopic Defect

“…This finding matches observations from previous studies in which it was suggested that the microstructure was responsible for the osteoinductive potential of biomaterials. 2,11,23,24 Although the exact mechanism of this process is still unknown, the fact remains that in this model BCP1150 somehow stimulated undifferentiated cells to generate bone at its surface. BCP1300 completely lacked this ability.…”

“…Osteoinduction has been shown in soft tissues of various animal models by a number of calcium-phosphate (CaP) containing bulk ceramics such as hydroxyapatite (HA), 2-9 a-tricalcium phosphate (a-TCP), b-TCP-, BCP, a-pyrophosphate, and b-pyrophosphate. 2,3,6,10 -18 Furthermore, ectopic bone formation has been observed by octacalcium phosphate (OCP)-coated porous biomaterials, 12,13,19 CaP cements, 11,20 and glass ceramics. 21 Osteoinduction has also been reported by porous alumina ceramic 22 and titanium.…”

“…25 In addition, a certain, not yet well-defined microstructure seems essential in osteoinduction. 2,11,15,17,22,23 Despite extensive research into osteoinductive properties of various biomaterials, the mechanism of osteoinduction remains largely unknown. Whether osteoinductive biomaterials first collect endogenous factors such as BMPs, which in turn trigger mesenchymal stem cells to start differentiation into the osteogenic lineage, or whether biomaterials directly trigger the differentiation due to their physicochemical properties and structure, needs further investigation.…”

The rational use of animal models in the evaluation of novel bone regenerative therapies

“…Biomaterials have a range of properties, from osteoinductive and osteoconductive to immunomodulatory. Hydroxyapatite and calcium phosphate as well as their composites such as HA/poly(DL-lactic-co-glycolic acid) (PLGA), in the form of ceramics, cements and coatings have shown osteoinduction in animal models [60][61][62][63][64][65][66]. Various hybrid materials combined as co-polymers, polymer blends and polymer-ceramic blends have also shown efficacy [67][68][69][70][71][72][73].…”

Alveolar bone regeneration in rats after grafting of anorganic bovine bone and thick synthetic bioceramic

“…14 The biological response of the host tissue to this type of material may vary according to its porosity, shape and size of particles, as well as their compositional characteristics, such as the amount of HA and βT C P. [15][16][17][18] HA-βTCP ceramics have been reported as biocompatible, osteoconductive and osteoinductive. The latter is due to being capable of differentiating mesenchymal stem cells into osteoblasts and chondroblasts.…”