Citations

AbstractDegenerative spinal pathology is a widespread medical issue, and spine fusion surgeries are frequently performed. In this study, we fabricated an injectable bioactive click chemistry polymer cement for use in spinal fusion and bone regrowth. Taking advantages of the bioorthogonal click reaction, this cement can be crosslinked by itself eliminating the addition of a toxic initiator or catalyst, nor any external energy sources like UV light or heat. Furthermore, nano‐hydroxyapatite (nHA) and microspheres carrying recombinant human bone morphogenetic protein‐2 (rhBMP‐2) and recombinant human vascular endothelial growth factor (rhVEGF) were used to make the cement bioactive for vascular induction and osteointegration. After implantation into a rabbit posterolateral spinal fusion (PLF) model, the cement showed excellent induction of new bone formation and bridging bone, achieving results comparable to autograft control. This is largely due to the osteogenic properties of nano‐hydroxyapatite (nHA) and the released rhBMP‐2 and rhVEGF growth factors. Since the availability of autograft sources is limited in clinical settings, this injectable bioactive click chemistry cement may be a promising alternative for spine fusion applications in addressing various spinal conditions.

Abstract Polycaprolactone fumarate (PCLF) is a cross‐linkable PCL derivative extensively considered for tissue engineering applications. Although injection molding has been widely used to develop PCLF scaffolds, platforms developed using such technique lack precise control on architecture, design, and porosity required to ensure adequate cellular and tissue responses. In particular, the scaffolds should provide a suitable surface for cell attachment and proliferation, and facilitate cell–cell communication and nutrient flow. 3D printing technologies have led to new architype for biomaterial development with micro‐architecture mimicking native tissue. Here, we developed a method for 3D printing of PCLF structures using the extrusion printing technique. The crosslinking property of PCLF enabled the unique post‐processing of 3D printed scaffolds resulting in highly porous and flexible PCLF scaffolds with compressive properties imitating natural features of cancellous bone. Generated scaffolds supported excellent attachment and proliferation of mesenchymal stem cells (MSC). The high porosity of PCLF scaffolds facilitated vascularized membrane formation demonstrable with the stringency of the ex ovo chicken chorioallantoic membrane (CAM) implantation. Furthermore, upon implantation to rat calvarium defects, PCLF scaffolds enabled an exceptional new bone formation with a bone mineral density of newly formed bone mirroring native bone tissue. These studies suggest that the 3D‐printed highly porous PCLF scaffolds may serve as a suitable biomaterial platform to significantly expand the utility of the PCLF biomaterial for bone tissue engineering applications.

Abstract A numerical investigation is conducted on the injury-related biomechanical parameters of the human head under blunt impacts. The objective of this research is twofold; first to understand the role of the employed finite element (FE) head model — with its specific components, shape, size, material properties, and mesh size — in predicting tissue responses of the brain, and second to investigate the fidelity of pressure response in validating FE head models. Accordingly, two independently established and validated FE head models are impacted in two directions under two impact severities and their predicted responses in terms of intracranial pressure (ICP) and shear stress are compared. The coup-counter ICP peak values are less sensitive to head model, mesh size, and the brain material. In all cases, maximum ICPs occur on the outer surface, vanishing linearly toward the center of the brain. Hence, it is concluded that different head models may simply reproduce the results of ICP variations due to impact. Shear stress prediction, however, is mainly affected by the head model, direction and severity of impact, and the brain material.

The spinal column is the most common site for bone metastasis. Vertebral metastases with instability have historically been treated with corpectomy of the affected vertebral body and adjacent intervertebral discs, and have more recently been treated with separation surgery. With demographics shifting towards an elderly population, a less-invasive surgical approach is necessary for the repair of vertebral defects. We modified a previously reported expandable hollow cage composed of an oligo[poly(ethylene glycol) fumarate] (OPF) containment system that could be delivered via a posterior-only approach. Then, the polymer of interest, poly (methyl methacrylate) (PMMA) bone cement, was injected into the lumen of the cage after expansion to form an OPF/PMMA cage. We compared six different cage formulations to account for vertebral body and defect size, and performed a cage characterization via expansion kinetics and mechanical testing evaluations. Additionally, we investigated the feasibility of the OPF/PMMA cage in providing spine stability via kinematic analyses. The in-vitro placement of the implant using our OPF/PMMA cage system showed improvement and mechanical stability in a flexion motion. The results demonstrated that the formulation and technique presented in the current study have the potential to improve surgical outcomes in minimally invasive procedures on the spine.

A wide range of materials have been used for the development of intervertebral cages. Poly(propylene fumarate) (PPF) has been shown to be an excellent biomaterial with characteristics similar to trabecular bone. Hydroxyapatite (HA) has been shown to enhance biocompatibility and mechanical properties of PPF. The purpose of this study was to characterize the effect of PPF augmented with HA (PPF:HA) and evaluate the feasibility of this material for the development of cervical cages. PPF was synthesized and combined with HA at PPF:HA wt:wt ratios of 100:0, 80:20, 70:30, and 60:40. Molds were fabricated for testing PPF:HA bulk materials in compression, bending, tension, and hardness according to ASTM standards, and also for cage preparation. The cages were fabricated with and without holes and with porosity created by salt leaching. The samples as well as the cages were mechanically tested using a materials testing frame. All elastic moduli as well as the hardness increased significantly by adding HA to PPF (p < 0.0001). The 20 wt % HA increased the moduli significantly compared to pure PPF (p < 0.0001). Compressive stiffness of all cages also increased with the addition of HA. HA increased the failure load of the porous cages significantly (p = 0.0018) compared with nonporous cages. PPF:HA wt:wt ratio of 80:20 proved to be significantly stiffer and stronger than pure PPF. The current results suggest that this polymeric composite can be a suitable candidate material for intervertebral body cages.

Blast traumatic brain injury (bTBI) may happen due to sudden blast and high-frequency loads. Due to the moral issues and the burden of experimental approaches, using computational methods such as finite element analysis (FEA) can be effective. Several finite element studies have focused on the effects of TBI to anticipate and understand the brain dynamic response. One of the most important factors in every FEA study of bTBI is the accurate modeling of brain tissue material properties. The main goal of this study is a comparison of different brain tissue constitutive models to understand the dynamic response of brain under an identical blast load. The multi-material FE modeling of the human head has several limitations such as its complexity and consequently high computational costs. Therefore, a spherical head model is modeled which suggests more straightforward observation/understanding of the FE modeling of skull (solid), CSF (fluid), and the brain tissue. Three different material models are considered for the brain tissue, namely hyperelastic, viscoelastic, and hyperviscoelastic. Brain dynamic responses are studied in terms of the head kinematics (linear acceleration), intracranial pressure (ICP), shear stress, and maximum mechanical strain. Our results showed that the hyperelastic model predicts larger ICP and shear than other constitutive brain tissue models. However, all material models predicted similar shear strain and head accelerations.

Skull deformation and vibration has been hypothesized to be an injury mechanism when the human head undergoes an impact scenario. The extent that skull deformation may increase the risk of traumatic brain injury, however, is not well understood. This computational study explains whether skull deformation has any impact on the variation of intracranial pressure (ICP). To this end, a finite element head model including major anatomical components of the human head was employed. The head model has been validated against ICP variations on the brain. The impact simulations were carried out using a rigid cylindrical impactor. The scenarios were frontal impacts with the impactor hitting the forehead of the head model at two impact severity levels. In order to examine the effect of skull elasticity on the stress wave propagation inside the cranium under an external applied force, the skull was also taken as a rigid body with the same density as the elastic one, and the result were compared with those obtained with the deformable skull. For the two cases, the variation of ICPs at the coup and countercoup sites were recorded and compared. The results of the study showed that, for the case studies presented here, the deformation of skull didn’t increase the level of ICP inside the brain. It was concluded that the skull rapid body motion might be responsible for brain injuries.