A programmable, fast-fixing, osteo-regenerative, biomechanically robust bone screw

Abstract

The use of a screw for repairing defected bones is limited by the dilemma between stiffness, bioactivity and internal fixation ability in current products. For polymer bone screw, it is difficult to achieve the bone stiffness and osteo-induction. Polymer composites may enhance bioactivity and mechanical properties but sacrifice the shape memory properties enormously. Herein, we fabricated a programmable bone screw which is composed of shape memory polyurethane, hydroxyapatite and arginylglycylaspartic acid to resolve the above problem. This composite has significantly improved mechanical and shape-memory properties with a modulus of 250 MPa, a shape fixity ratio of ~90% and a shape recovery ratio of ~96%. Moreover, shape fixity and recovery ratios of the produced SMPC screw in the simulative biological condition were respectively ~80% and ~82%. The produced screw could quickly recover to its original shape in vitro within 20 s leading to easy internal fixation. Additionally, the composite could support mesenchymal stem cell survival, proliferation and osteogenic differentiation in vitro tests. It also promoted tissue growth and showed beneficial mechanical compatibility after implantation into a rabbit femoral intracondyle for 12 weeks with little inflammation. Such bone screw exhibited a fast-fixing, tightened fitting, enhanced supporting and boosted bioactivity simultaneously in the defective bone, which provides a solution to the long-standing problem for bone repairing. We envision that our composite material will provide valuable insights into the development of a new generation of bone screws with good fixation and osteogenic properties.

Statement of Significance

The main obstacles to a wider use of a bone screw are unsatisfied stiffness, inflammatory response and screw loosening issues. Herein, we report a programmable screw with mechanically robust, bioactive and fast-fixing performances. The shape memory polymer composite takes advantage of the component in the natural bone and possesses a stable bush-like structure inside through the covalent bonding, and thus achieve significantly improved mechanical and memory properties. Based on its shape memory effect, the produced screw was proved to offer a recovery force to surroundings and promote the bone regeneration effectively. Therefore, the composite realizes our expectations on functions through structure design and paves a practical and effective way for the development of a new generation of bone screws.

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.