Lumbar interbody fusion with porous biphasic calcium phosphate enhanced by recombinant bone morphogenetic protein-2/silk fibroin sustained-released microsphere: an experimental study on sheep model

Abstract

Biphasic calcium phosphate (BCP) has been investigated extensively as a bone substitute nowadays. However, the bone formation capacity of BCP is limited owing to lack of osteoinduction. Silk fibroin (SF) has a structure similar to type I collagen, and could be developed to a microsphere for the sustained-release of rhBMP-2. In our previous report, bioactivity of BCP could be enhanced by rhBMP-2/SF microsphere (containing 0.5 µg rhBMP-2) in vitro. However, the bone regeneration performance of the composite in vivo was not investigated. Thus, the purpose of this study was to evaluate the efficacy of BCP/rhBMP-2/SF in a sheep lumbar fusion model. A BCP and rhBMP-2/SF microsphere was developed, and then was integrated into a BCP/rhBMP-2/SF composite. BCP, BCP/rhBMP-2 and BCP/rhBMP-2/SF were implanted randomly into the disc spaces of 30 sheep at the levels of L1/2, L3/4 and L5/6. After sacrificed, the fusion segments were evaluated by manual palpation, CT scan, biomechanical testing and histology at 3 and 6 months, respectively. The composite demonstrated a burst-release of rhBMP-2 (39.1 ± 2.8 %) on the initial 4 days and a sustained-release (accumulative 81.3 ± 4.9 %) for more than 28 days. The fusion rates, semi-quantitative CT scores, fusion stiffness in bending in all directions and histologic scores of BCP/rhBMP-2/SF were significantly greater than BCP and BCP/rhBMP-2 at each time point, respectively (P < 0.05). These findings indicate that the SF microspheres containing a very low dose of rhBMP-2 improve fusion in sheep using BCP constructs.

Evaluation of lumbar spinal fusion utilizing recombinant human platelet derived growth factor‐B chain homodimer (rhPDGF‐BB) combined with a bovine collagen/β‐tricalcium phosphate (β‐TCP) matrix in an ovine model

“…The density of the sheep bone used in preclinical orthopedic investigations is typically much greater than that of the target human population for these treatments, and the removal of tissue from the endplates allows for a closer representation of clinical human vertebral bone 32 . It is known that decorticating the bone leads to greater bone formation, therefore removal of tissue from the endplates may have increased the bone formation for all treatments and encouraged callus bone growth around the anterior region of the vertebral body and interbody cage 33‐35 . It is also possible that preservation of the intervertebral endplates may have resulted in decreased bone growth, particularly in sham control animals.…”

“… 32 It is known that decorticating the bone leads to greater bone formation, therefore removal of tissue from the endplates may have increased the bone formation for all treatments and encouraged callus bone growth around the anterior region of the vertebral body and interbody cage. 33 , 34 , 35 It is also possible that preservation of the intervertebral endplates may have resulted in decreased bone growth, particularly in sham control animals. While the interbody cages were implanted as uniformly as possible, some slight variability in the final placement of the interbody cages is inherent due to the manual implantation process.…”

Silk Protein-Mediated Biomineralization: From Bioinspired Strategies and Advanced Functions to Biomedical Applications

“…MSA is a process by which stable polymers are formed between molecules through noncovalent bonds at the molecular level. , This method involves the use of silk proteins as a template to form mineral structures through the self-assembly of inorganic ions with organic molecules. The self-assembly process is driven by noncovalent interactions between the inorganic and organic components, resulting in the formation of a mineralized composite with controllable size and shape.…”

Preparation of silk fibroin carriers for controlled release

“…The efficacy of BCP with these rhBMP‐2/SF microspheres were evaluated in a sheep lumbar fusion model. The in vivo results showed that the silk fibroin microspheres including a very low dose of rhBMP‐2 could improve fusion in sheep using BCP constructs (Chen et al, ).…”