A fast degradable citrate-based bone scaffold promotes spinal fusion

Abstract

It is well known that high rates of fusion failure and pseudoarthrosis development (5~35%) are concomitant in spinal fusion surgery, which was ascribed to the shortage of suitable materials for bone regeneration. Citrate was recently recognized to play an indispensable role in enhancing osteconductivity and osteoinductivity, and promoting bone formation. To address the material challenges in spinal fusion surgery, we have synthesized mechanically robust and fast degrading citrate-based polymers by incorporating N-methyldiethanolamine (MDEA) into clickable poly(1, 8-octanediol citrates) (POC-click), referred to as POC-M-click. The obtained POC-M-click were fabricated into POC-M-click-HA matchstick scaffolds by compositing with hydroxyapatite (HA) for interbody spinal fusion in a rabbit model. Spinal fusion was analyzed by radiography, manual palpation, biomechanical testing, and histological evaluation. At 4 and 8 weeks post surgery, POC-M-click-HA scaffolds presented optimal degradation rates that facilitated faster new bone formation and higher spinal fusion rates (11.2±3.7, 80±4.5 at week 4 and 8, respectively) than the poly(L-lactic acid)-HA (PLLA-HA) control group (9.3±2.4 and 71.1±4.4) (p<0.05). The POC-M-click-HA scaffold-fused vertebrates possessed a maximum load and stiffness of 880.8±14.5 N and 843.2±22.4 N/mm, respectively, which were also much higher than those of the PLLA-HA group (maximum: 712.0±37.5 N, stiffness: 622.5±28.4 N/mm, p<0.05). Overall, the results suggest that POC-M-click-HA scaffolds could potentially serve as promising bone grafts for spinal fusion applications.

Citrate-based materials fuel human stem cells by metabonegenic regulation

“…The impressive in vivo performances of existing citrate-presenting materials in bone regeneration, demonstrated through numerous animal models (12,13,(31)(32)(33), motivated us to investigate the biological mechanism of citrate action on bone development. The present study has identified citrate as an osteopromotive factor; specifically, its beneficial effects are mediated by SLC13a5, the plasma membrane transporter responsible for citrate uptake.…”

Citrate chemistry and biology for biomaterials design

“…For example, collagen mimetic peptide P15 that promotes endothelial cell adhesion and proliferation has been successfully conjugated to POC-click through strain-promoted azide-alkyne cycloaddition (SPAAC), another click reaction performed in aqueous solution at room or body temperature. MDEA can be further incorporated in the POC-click backbone [34] which is beneficial through acceleration of the degradation rate of POC-M-click, counteracting the delayed polymer degradation caused by the rigid triazole rings of POC-click.…”

“…A series of new citrate-based biodegradable elastomers have recently been developed to composite with HA. Such composites have subsequently been fabricated into different modalities, such as porous cylindrical or disk-like [13, 72, 144] scaffolds [34], and biphasic scaffolds [145]. For example, the mechanically strong CUPE and POC-Click have been composited with 65 wt% HA to fabricate disk-shaped scaffolds with 70% porosity [144], and their efficacy as bone grafts has been evaluated in a critical-sized cranial defect model.…”

“…The promising in vivo bone responses of citrate-based composite in bridging defects and promoting bone formation motivated the development of CBB/HA composites for other specific regeneration applications, such as spinal fusion [34], comminuted bone fracture healing [73] and bone-tunnel healing during ligament reconstruction [149]. For example, spinal fusion is a surgical procedure, responsible for 50% of bone transplantations, that fuses two or more vertebrae into one single structure for the treatment of cervical vertebra instability, intervertebral disc injury, spinal degeneration and deformity [150].…”

Flexible biodegradable citrate-based polymeric step-index optical fiber

“…Unlike natural materials (e.g., silk) or traditional synthetic polymers (e.g., poly lactic-co-glycolic acid (PLGA)) that usually have limited tunability for key optical, mechanical, and/or degradation properties, the family of citrate-based biodegradable elastomers possesses tunable mechanical strengths (from tens of Pascal to mega Pascal), programmable degradation rates (from a few days to over a year), reactive nature between citrate-based polymers, multi-functionalities (e.g., adhesive, fluorescent)[14], and as shown in this work, ultrafine tuning of refractive index (~10 −3 )(Figure 1c). Citrate-based elastomers have been used as implant materials for diverse applications such as soft tissue engineering (blood vessel, nerve, and skin)[15–17], bone tissue engineering[18–21], wound healing and bioadhesives[22–26], theranostic nanoparticles for cancer imaging and drug delivery[12,27–33], and biosensing[34]. Therefore, citrate-based elastomers serve as an ideal material platform for the development of fully biodegradable and seamlessly integrated step-index optical fibers for in vivo applications.…”