Osteoinductive Ceramics Research Articles

Synergistic effect of Wnt modulatory small molecules and an osteoinductive ceramic on C2C12 cell osteogenic differentiation

Although osteoinductive ceramics can induce osteoblast differentiation in vitro and bone regeneration in vivo, their effects rely solely on the limited number of endogenous stem cells. More recently, ceramic carriers seeded with culture-expanded stem cells have been reported as implants capable of in vivo bone formation. However, effective and safe signaling agents that promote cell differentiation to the osteogenic lineage are still needed. In the present report, two osteogenic small-molecules THQ-1a and PP-9 were identified by testing a series of compounds for Runx2 and BMP2 expression in C2C12 cells. Compounds THQ-1a and PP-9 modulated Wnt signaling and enhanced the expression of molecular markers of osteoblast differentiation. To probe the utility of these compounds for use with ceramic cell implants, the effect of THQ-1a and PP-9 on C2C12 cell osteogenic differentiation was investigated in the presence of a tricalcium phosphate (TCP) ceramic. The effect of THQ-1a and PP-9 on markers such as Osteocalcin and Collagen I was significantly increased in the presence of TCP ceramic. Additionally, THQ-1a or PP-9 in the presence of TCP ceramic gave a synergistic increase in alkaline phosphatase activity in the differentiation of C2C12 cells. Taken together, the results suggest an approach to directing cell lineage commitment for bone regeneration by the application of small-molecule osteogenic agents to cells in the presence of osteoinductive ceramics.

Osteoinductive ceramics as a synthetic alternative to autologous bone grafting

Biomaterials can be endowed with biologically instructive properties by changing basic parameters such as elasticity and surface texture. However, translation from in vitro proof of concept to clinical application is largely missing. Porous calcium phosphate ceramics are used to treat small bone defects but in general do not induce stem cell differentiation, which is essential for regenerating large bone defects. Here, we prepared calcium phosphate ceramics with varying physicochemical and structural characteristics. Microporosity correlated to their propensity to stimulate osteogenic differentiation of stem cells in vitro and bone induction in vivo. Implantation in a large bone defect in sheep unequivocally demonstrated that osteoinductive ceramics are equally efficient in bone repair as autologous bone grafts. Our results provide proof of concept for the clinical application of "smart" biomaterials.

Comparative in vivo study of six hydroxyapatite‐based bone graft substitutes

Improvement of synthetic bone graft substitutes as suitable alternatives to a patient's own bone graft remains a challenge in biomaterials research. Our goal was to answer the question of whether improved osteoinductivity of a material would also translate to better bone-healing orthotopically. Three porous biphasic calcium phosphate (BCP) ceramics (BCPA, BCPB, and BCPC), consisting of hydroxyapatite and beta-tricalcium phosphate, a porous biphasic calcium phosphate ceramic reinforced with a bioresorbable polylactic acid to improve its mechanical properties (BCPC+), a pure hydroxyapatite ceramic (HA), and a carbonated apatite ceramic (CA) were implanted intramuscularly and orthotopically by using a transverse process model in 11 goats for 12 weeks. BCPA and BCPB had similar chemical composition but differed in their microstructure. BCPB was not osteoinductive at all, but BCPA induced ectopic bone formation in 9 of 11 animals. Orthotopically, BCPA performed better than BCPB in both the amount and rate of bone formation. BCPC, similar to BCPA structurally and physicochemically, showed comparable results ectopically and orthotopically. Addition of resorbable polymer to BCPC made the material less osteoinductive (4 of 11 animals) and delayed bone formation orthotopically. Neither HA nor CA were osteoinductive, and their orthotopic performance was inferior to the osteoinductive ceramics. The results of the present study showed that material-derived osteoinduction significantly enhanced bone healing orthotopically, and that this material property appeared more sensitive for predicting orthotopic performance than physicochemical and structural characteristics.

Knochentransplantation — Indikation und Technik

Autogenous spongiosa or, in osteoplastic surgery, autogenous corticospongious bones are considered as substance of choice for the surgical transposition of missing bones, to strengthen bones with insufficient loading capacity, and for a biological activation of atrophic bones. Even deep-freeze allogenous spongiosa can be inserted into a sterile, stable implantation site able to absorb the spongiosa to a large extent. The success will be delayed, but in the end a good functional result will be achieved with this method. In case of such an optimum implantation site, a comparable therapeutic effect can also be obtained with osteoinductive ceramics which can be modified with respect to their osteoinduction and loading capacity, both values showing a reciprocal ratio. Xenogenous bone grafts are no longer applied. A clinical example is presented in order to describe some criteria for the choice of a suitable transplant and to give some practical indications for its therapeutic application.