3D-bioimplants mimicking the structure and function of spine units for the treatment of spinal tuberculosis

Abstract

Approximately 1–2% of the reported tuberculosis (TB) cases have skeletal system problems, particularly spinal TB. The complications of spinal TB involve the destruction of vertebral body (VB) and intervertebral disc (IVD) which consequently leads to kyphosis. This work aimed at utilizing different technologies to develop, for the first time, a functional spine unit (FSU) replacement to mimic the structure and function of the VB and IVD along with a good ability to treat spinal TB. 3D-printed scaffolds with different porous patterns (hexagonal or grid) were fabricated from biocompatible acrylonitrile butadiene styrene, and polylactic acid to replace damaged VB and IVD, respectively. The VB scaffold is filled with gelatine-based semi-IPN hydrogel containing mesoporous silica nanoparticles loaded with two antibiotics, rifampicin and levofloxacin, to act against TB. The IVD scaffold incorporates a gelatin hydrogel loaded with regenerative platelet-rich plasma and anti-inflammatory simvastatin-loaded mixed nanomicelles. The obtained results confirmed the superior mechanical strength of both 3D-printed scaffolds and loaded hydrogels as compared to normal bone and IVD with high in vitro (cell proliferation, anti-inflammation and anti-TB), and in vivo biocompatibility profiles. Moreover, the custom-designed replacements have achieved the expected prolonged release of antibiotics up to 60 days. Given the promising study findings, the utilization of the developed drug-eluting scaffold system can be extrapolated to treat not only spinal TB but also to resolve diverse backbone/spine problems that need a critical surgical process including degenerative IVD and its consequences like atherosclerosis, sliding or spondylolisthesis and severe traumatic bone fracture.