Co-delivery of rhBMP-2 and zoledronic acid using calcium sulfate/hydroxyapatite carrier as a bioactive bone substitute to enhance and accelerate spinal fusion.

Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been FDA-approved for lumbar fusion, but supraphysiologic initial burst release due to suboptimal carrier and late excess bone resorption caused by osteoclast activation have limited its clinical usage. One strategy to mitigate the pro-osteoclast side effect of rhBMP-2 is to give systemic bisphosphonates, but it presents challenges with systemic side effects and low local bioavailability. The aim of this in vivo study was to analyze if posterolateral spinal fusion (PLF) could be improved by utilizing a calcium sulfate/hydroxyapatite (CaS/HA) carrier co-delivering rhBMP-2 and zoledronic acid (ZA). Six groups were allocated (CaS/HA, CaS/HA + BMP-2, CaS/HA + systemic ZA, CaS/HA + local ZA, CaS/HA + BMP-2 + systemic ZA, and CaS/HA + BMP-2 + local ZA). 10-week-old male Wistar rats, were randomly assigned to undergo L4-L5 PLF with implantation of group-dependent scaffolds. At 3 and 6 weeks, the animals were euthanized for radiography, µCT, histological staining, or biomechanical testing to evaluate spinal fusion. The results demonstrated that the CaS/HA biomaterial alone or in combination with local or systemic ZA didn't support PLF. However, the delivery of rhBMP-2 significantly promoted PLF. Combining systemic ZA with BMP-2 didn't enhance spinal fusion. Notably, the co-delivery of rhBMP-2 and ZA using the CaS/HA carrier significantly enhanced and accelerated PLF, without inhibiting systemic bone turnover, and potentially reduced the dose of rhBMP-2. Together, the treatment regimen of CaS/HA biomaterial co-delivering rhBMP-2 and ZA could potentially be a safe and cost-effective off-the-shelf bioactive bone substitute to enhance spinal fusion.

[Computation and experimental examination of an implant structure made by a fibre-reinforced building method for the bypass of continuity defects of the mandible]. / Berechnung und experimentelle Prüfung einer Implantatstruktur in Faserverbundbauweise für die Uberbrückung von Kontinuitätsdefekten des Unterkiefers.

A partial resection of the lower jaw often has to be carried out in the context of the surgical removal of tumours in the lower jaw, mouth and tongue-floor space and lower jaw fractures with loss of substance, benign bone lesions and extensive difficult inflammation of bone tissue, respectively. The primary reconstruction of the lower jaw after partial resection with loss of continuity is mainly important for functional and aesthetic reasons. The defects of lower jaw continuity are often bridged with metal plates to reconstruct the masticatory function of the lower jaw, temporarily or permanently. Functional as well as aesthetic disadvantages arise in the case of the application of such plates as a result of a high stiffness jump between reconstruction plate and bone and their insufficiently individual design. The employment of biocompatible, carbon-fibre-reinforced Polyetheretherketon (CF-PEEK) permits the development of a geometry- and stiffness-adapted carrying structure for the mandible. For the demand-adapted dimensioning and the test of a CF-PEEK bandage, the application of optical methods, such as the grey value correlation method, is suited as well as numeric methods, such as the finite element method. In an initial analysis of deformation behaviour, the various osteosynthesis configurations are comparatively investigated on a model jaw. The calculations and tests of the lower jaw model show that the use of the new CF-PEEK bandage compared to the use of conventional titanium osteosynthesis plates shows a mechanical behaviour which is much better adapted to the natural lower jaw.