Rezaei, Asghar

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.

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.

ABSTRACT Although a large number of studies have addressed the age-related changes in bone mineral density (BMD), there is a paucity of data for the assessment of femoral strength loss with age in both genders. We determined the variation of strength with age in femurs of women and men by mechanical tests on a cohort of 100 cadaveric femurs. In addition, the age-related neck BMD loss in our cadaveric cohort was found to be similar with BMD loss of four published population-based studies. Given the strong correlation found in our cadaveric study between BMD and femoral strength, we also estimated the femoral strength of the four populations based on their reported neck BMDs. Our study showed that men's femurs in our cadaveric cohort were stronger than women's femurs by about 800 N at the same BMD level, and by 1750 N at the same age. The strength differences were not explained satisfactorily by the size difference between men's and women's bones. Similar to the findings of clinical studies, the BMD values of men at all ages were larger than that of women. The age-related loss rates in BMD and strength were not statistically different between the two genders of our cadaveric cohort. After normalization, strength decreased more than 40% faster than BMD. On average, men reached a certain BMD value about 16 years later than women, and for strength about 23 years later, which may explain the higher rate of hip fracture in postmenopausal women. In patient population cohorts men reached a similar BMD value about 16 to 25 years later than women, whereas for estimated strength, sometimes more than 40 years later. © 2015 American Society for Bone and Mineral Research.