Full length articleA programmable, fast-fixing, osteo-regenerative, biomechanically robust bone screw
Graphical abstract
Introduction
The fixation devices are commonly used in surgical treatments of bone defects to improve bone self-healing ability. It is estimated that the treatment for osteoporotic vertebral fracture costs 18 billion USD per year for more than 1.5 million fracture patients in the United States alone [1], [2], [3], [4], [5]. Bone screw, one of the common fixation devices, has been developed to fix fragments of the fractured bone or support defective sites over decades [6], [7], [8]. Traditionally, bone screws are mainly made of metals due to their considerable stiffness. However, an overly-high modulus of metal implants often leads to unexpected behaviors, e.g., the stress shielding effect, which may result in bone resorption and screw loosening [9]. Moreover, metallic materials (e.g. stainless steel) may cause inflammation and exhibit poor osseointegration due to their chemical dissimilarity to the natural bone [6,10,11]. Ceramics (e.g., hydroxyapatite, HA) with similar chemical structures to bone have thus been developed. These materials exhibit good osseointegration but suffered from fragility. Accordingly, composite materials (e.g. polymers and HA) have been further studied [12,13]. However, the clinical success of bone screws made of composite materials is still limited due to the unstable fixation caused by the insufficient support and inadequate friction to the surroundings [4,14].
Shape memory polymers (SMPs) bring a new fixation concept to bone healing. These materials can memorize and recover to their original shapes after deformation when being exposed to an external stimulus such as high temperature [15], light [16], electricity [17] or water [18]. For example, a thermal-responsive SMP can be programmed to a small size or targeted shape in advance before implantation into a defect site; at the transition temperature, the temporary shape will recover to its original state, fitting and supporting the damaged bone. Such shape deformation and recovery properties can minimize the damage to bones during implantation [19]. Furthermore, the SMP's recovery/expand process will strengthen the contact between the material and the surrounding tissue, making loosening almost impossible [20]. Previously, our group have developed thermal-responsive SMPs made of polyurethane. Such materials possess several advantages including low cost, a high capability of deformation, structure versatility and processability [5,[20], [21], [22]]. These materials have been successfully applied in self-fitting bone scaffold [23], shape memory vascular graft [24] and heart scaffold [25]. However, the modulus of the developed pristine SMP is ~10–100 MPa, making it less ideal for bone regeneration (cancellous bone has modulus of ~100–1000 MPa [26,27]). Incorporating nanoparticles like carbon nanotubes may increase its mechanical properties while the shape memory effect (SME) may be compromised due to the agglomeration of nanoparticles inside the polymer [28,29]. Therefore, to develop a shape memory polyurethane (SMPU) with enhanced mechanical properties without sacrificing its shape-memory properties is highly sought after.
Here, to address the cohered requirements and limitations of stiffness, bioactivity and internal fixation ability of existing products for the practical applications in bone repair, we propose a robust shape memory polymer composite (SMPC) screw made of SMPU/HA/arginylglycylaspartic acid (RGD) composite with improved fixation and osteogenic properties in bone regeneration. HA is selected due to its structural similarity to natural bone and osteoinductivity and osteoconductivity [30,31]. It was incorporated into the SMPU oligomers through the bonding between OH- and NCO- groups followed by chain extension (Fig. 1A). We first expect such covalent bonding between HA nanoparticles and polyurethane (PU) to circumvent the agglomeration issues and achieve enhanced mechanical performances without sacrificing the SME. RGD peptide was used to modify the composite surface property to promote cell adhesion [32], [33], [34]. We evaluate the in vitro cell behaviors including cell viability and proliferation as well as the organic properties using the SMP and its composites. Furthermore, the produced SMPC screw was investigated on the bone tissue growth and biomechanical performance through the in vivo experiment. Our expectation is that the SMPU/HA/RGD bone screws could reduce the probability of screw loosening and enhance the bioactive integration for improved bone regeneration. Altogether, our SMPU/HA/RGD bone screw exhibits a fast-fixing, enhanced supporting, tighten fitting and repairing ability in the defective bone; it paves way for the design and development of a new generation of bone screws with advanced performances for bone repair.
Section snippets
Materials
Polycaprolactone (PCL)-diol (Wn~550, CAPA2054) was obtained from Perstorp (Shanghai, China) Chemical Industry co., LTD. HA nanoparticles with a particle size of 20 nm were purchased from Emperor Nano Material Co. Ltd. (Nanjing, China) [23]. 4,4-methylenebis (phenylisocyanate) (MDI), 1,4-Butanediol (BDO), RGD sequences were purchased from Sigma-Aldrich (Shanghai, China). The PCL-diol and BDO were dried under vacuum at 100 °C for 24 h to remove the moisture in advance. HA and RGD were used as
Characterizations of SMP and its composites
Fig. 2A1 displays the magnified view in FTIR spectra of SMP and its composites. In comparison with unmodified SMP, the strong absorption band at 1056 cm−1 (PO43−) proved the presence of HA domains in the composite. After being modified with RGD, the characteristic absorption bands of Amide I and Amide II from RGD molecules at 1613 cm−1 and 1433 cm−1 were enhanced slightly compared to SMP/HA [52], suggesting the disperion of RGD in the composite. Fig. 2A2 is the Raman spectra which confirmed the
Discussion
Existing clinical bone screws are usually limited by the unstable fixation and the SMPC materials usually own good mechanical properties but sacrifice its SMEs. Therefore, this study demonstrates that the improved performances including mechanical, memory and the biological properties of SMPU/HA/RGD through the in vitro and in vivo experiments. At first, the swelling test proves the crosslinked structure of the SMP composites (Fig. 2B), which was regarded as the stable construction of the
Conclusions
A programmable bone screw made of the SMP/HA/RGD composite with a highly effective healing and supporting ability is developed in this study for addressing the limitations on stiffness, bioactivity and internal fixation ability in conventional screw implants. This SMPC screw takes advantage of its components and structure to achieve our expectations on shape memory effect, cytocompatibility, fixation and osteogenic properties. The in vitro experimental results demonstrated that the SMP/HA/RGD
Declaration of Competing Interest
The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
Acknowledgements
We gratefully acknowledge the help from Tissue Engineering Lab in the West China Hospital of Sichuan University and the support from the Shenzhen biological, new energy, new material industry development special funds on ‘Intelligent Bone Repair using shape memory polymers as biomedicine materials’ [Project code: JC201104210132A], start-up fund [1-ZE7S], central research fund [G-YBWS] and intra-faculty fund [1-ZVPC] from the Hong Kong Polytechnic University.
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2022, Bioactive MaterialsCitation Excerpt :Moreover, a better fitting of the scaffold to the patients defect shape and size could be achieved with this approach. Different bioactive agents have been incorporated into SMPs, including hydroxyapatite [22–24], polydopamine [9], proteins [24] and chondrogenic molecules [14]. An additional advantage of SMPs is their easy processability, enhancing their possibility of applications.