Effects of a bone graft substitute consisting of porous gradient HA/ZrO₂and gelatin/chitosan slow‐release hydrogel containing BMP‐2 and BMSCs on lumbar vertebral defect repair in rhesus monkey

Abstract

Dense biomaterial plays an important role in bone replacement. However, it fails to induce bone cell migration into graft material. In the present study, a novel bone graft substitute (BGS) consisting of porous gradient hydroxyapatite/zirconia composite (PGHC) and gelatin/chitosan slow-release hydrogel containing bone morphogenetic protein 2 and bone mesenchymal stem cells was designed and prepared to repair lumbar vertebral defects. The morphological characteristics of the BGS evaluated by a scanning electron microscope showed that it had a three-dimensional network structure with uniformly distributed chitosan microspheres on the surfaces of the graft material and the interior of the pores. Then, BGS (Group A), PGHC (Group B), or autologous bone (Group C) was implanted into lumbar vertebral body defects in a total of 24 healthy rhesus monkeys. After 8 and 16 weeks, anteroposterior and lateral radiographs of the lumbar spine, microcomputed tomography, histomorphometry, biomechanical testing, and biochemical testing for bone matrix markers, including Type I collagen, osteocalcin, osteopontin, basic fibroblast growth factor, alkaline phosphatase, and vascular endothelial growth factor, were performed to examine the reparative efficacy of the BGS and PGHC. The BGS displayed excellent ability to repair the lumbar vertebral defect in rhesus monkeys. Radiography, microcomputed tomography scanning, and histomorphological characterization showed that the newly formed bone volume in the interior of the pores in the BGS was significantly higher than in the PGHC. The results of biomechanical testing indicated that the vertebral body compression strength of the PGHC implant was lower than the other implants. Reverse-transcription polymerase chain reaction and western blot analyses showed that the expression of bone-related proteins in the BGS implant was significantly higher than in the PGHC implant. The BGS displayed reparative effects similar to autologous bone. Therefore, BGS use in vertebral bone defect repair appears promising.

Enhanced osseointegration of three-dimensional supramolecular bioactive interface through osteoporotic microenvironment regulation

“…BMSCs and BMP-2 are the common seed cells and growth factor for bone regeneration, respectively, and have been incorporated into scaffolds to enhance bone generation [48]. Hydrogel, as a sustained release system, containing BMSCs and BMP-2 could effectively repair bone defects [49]. However, there are limited studies on the use of hydrogels as cells or drug carriers to fill porous metal implants.…”

Chitosan-Based Biomaterial Scaffolds for the Repair of Infected Bone Defects

“…Moreover, antibiotics cannot reach the osteomyelitis site at a sufficient concentration, resulting in limited efficacy and poor patient compliance ( Orhan et al, 2006 ). For the reconstruction of local bone defects, autografts, allografts, masquelet membrane induction technology, and bone transfer technology are currently the most effective methods ( Cui et al, 2017 ; Ye et al, 2018a ; Shao et al, 2018 ). However, they are also associated with problems, such as the need for extra surgery, increased hospitalization time, donor site morbidity, and the occurrence of stress fractures ( Keller et al, 2017 ; Radwan et al, 2020 ).…”

Engineering biological gradients

“…Indeed, these kinds of structures require pre-operative treatments that substantially modify the sample, such as freeze-drying or ethanol dehydration. 93,109,110 Scanning electron microscopy is a common technique used to characterize material surfaces. Scanning electron microscopy can give information about the topography of the material, such as roughness, 111 fiber orientation, and diameter, 112 as well as particle coating distributions, 79,113 but it can also capture variations in cell adhesion and proliferation.…”

“…Indeed, these kinds of structures require pre-operative treatments that substantially modify the sample, such as freeze-drying or ethanol dehydration. 93, 109, 110…”