Liu, Xifeng

AbstractA current approach in bone tissue engineering is the implantation of polymeric scaffolds that promote osteoblast attachment and growth as well as biomineralization. One promising polymer is oligo[poly(ethylene glycol) fumarate] (OPF), a polyethylene glycol‐based material that is biocompatible, injectable, and biodegradable, but in its native form does not support robust bone cell attachment or growth. To address this issue, this study evaluated the osteoconductivity of bis[02‐(methacryloyloxy)ethyl] phosphate (BP) functionalized OPF hydrogels (OPF‐BP) using MC3T3‐E1 pre‐osteoblast cells, both before and after enzymatic mineralization with a calcium solution. The inclusion of negatively charged functional groups allowed for the tailored uptake and release of calcium, while also altering the mechanical properties and surface topography of the hydrogel surface. In cell culture, OPF‐BP hydrogels with 20 and 30% (w/w) BP optimized osteoblast attachment, proliferation, and differentiation after a 21‐day in vitro period. In addition, the OPF‐BP30 treatment, when mineralized with calcium, exhibited a 128% increase in osteocalcin expression when compared with the non‐mineralized treatment. These findings suggest that phosphate functionalization and enzymatic calcium mineralization can act synergistically to enhance the osteoconductivity of OPF hydrogels, making this processed material an attractive candidate for bone tissue engineering applications.

Biomaterials that act as both protein delivery vehicle and scaffold can improve the safety and efficacy of bone morphogenetic protein-2 (BMP-2) for clinical applications. However, the optimal scaffold characteristics are not known. The osteoinductive and osteoconductive capacity of a fixed electrically charged surface is thus far unexplored. Therefore, in this study, we aim to investigate the effect of different electrical states on BMP-2-induced bone formation in oligo[(polyethylene glycol) fumarate] (OPF) hydrogels. Neutral, negatively, or positively charged scaffolds were fabricated using unmodified OPF (neutral charge), sodium methacrylate crosslinked OPF (negative charge), or [2-(methacryloyloxy) ethyl] trimethylammonium chloride crosslinked OPF (positive charge), respectively. To allow investigation of surface charge for different BMP-2 release rates, three BMP-2 release profiles were generated by protein encapsulation into poly(lactic-co-glycolic acid) microspheres and/or adsorption on the OPF composite. Release of radiolabeled 125 I-BMP-2 was analyzed in vitro and in vivo and bone formation was assessed after 9 weeks of subcutaneous implantation in rats. Negatively charged OPF generated significantly more bone formation compared with neutral and positively charged OPF. This effect was seen for all three loading methods and subsequent BMP-2 release profiles. Along with charge modifications, a more sustained release of BMP-2 improved overall bone formation in OPF composites. Overall, this study clearly shows that negative charge enhances bone formation compared with neutral and positive charge in OPF composites. Impact Statement Biomaterials can play a dual role in bone regeneration: they enable local sustained delivery of growth factors, such as bone morphogenetic protein-2 (BMP-2), while they provide structural support as scaffold. By better imitating the properties of native bone tissue, scaffolds may be both osteoconductive and osteoinductive. The latter can be achieved by modifying the electrical charge of the surface. The present work uses tunable oligo[(polyethylene glycol) fumarate] hydrogel and demonstrates that negative charge enhances BMP-2-induced bone formation compared with neutral or positive charge. Altogether, this indicates that tissue-specific surface charge modifications of biomaterials hold great promise in the field of tissue regeneration.

Strain-promoted alkyne–azide cycloaddition (SPAAC) click chemistry was applied for the rapid conjugation of nanoparticles, proteins, and siRNA-micelles to ultrasound microbubbles.

Abstract Incorporation of hydroxyapatite (HA) into polymer networks is a promising strategy to enhance the mechanical properties and osteoinductivity of the composite scaffolds for bone tissue engineering. In this study, we designed a group of nanocomposite scaffolds based on cross‐linkable poly(propylene fumarate) (PPF) and 30 wt % strontium‐hydroxyapatite (Sr‐HA) nanoparticles. Four different Sr contents [Sr:(Sr + Ca), molar ratio] in the Sr‐HA particles were studied: 0% (HA), 5% (Sr5‐HA), 10% (Sr10‐HA), and 20% (Sr20‐HA). Two‐dimensional (2D) disks were prepared using a thermal crosslinking method. The structure and surface morphology of different Sr‐HA and PPF/Sr‐HA composites were characterized using scanning electron microscopy (SEM), energy‐dispersive X‐ray spectroscopy (EDS), transmission electron microscopy (TEM), and atomic force microscopy (AFM). To detect cellular responses in vitro, MC3T3‐E1 cells were seeded and cultured on the different PPF/Sr‐HA composite disks. Cell morphology after 24 h and 5 days were imaged using Live/Dead live cell staining and SEM, respectively. Cell proliferation was quantified using an MTS assay at 1, 4, and 7 days. Osteogenic differentiation of the cells was examined by alkaline phosphatase (ALP) staining at 10 days and quantified using ALP activity and osteocalcin assays at 7, 14, and 21 days. The sizes of the HA, Sr5‐HA, Sr10‐HA, and Sr20‐HA particles were mainly between 10 × 20 nm and 10 × 250 nm, and these nanoparticles were dispersed or clustered in the composite scaffolds. in vitro cell studies showed that the PPF/Sr10‐HA scaffold was significantly better than the other three groups (PPF/HA, PPF/Sr5‐HA, and PPF/Sr20‐HA) in supporting MC3T3‐E1 cell adhesion, proliferation, and differentiation. PPF/Sr10‐HA may, therefore, serve as a promising scaffold material for bone tissue engineering. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 107A: 631–642, 2019.

Electrically conductive hydrogels incorporated with CNTs support PC12 cell growth and differentiation and hold promise for nerve regeneration.

Current delivery of chemotherapy drugs to osteosarcoma is limited by the difficulties in overcoming the solid tumor microenvironment and the cardiotoxicity of doxorubicin (DOX). In previous work we found that phase separation could generate microspheres with high porosity. In this study, we applied these phase-separated porous microspheres as carriers for long-term anticancer drug delivery. Novel poly(propylene fumarate)- co -poly( l -lactic acid) microspheres incorporating DOX were fabricated by thermally induced phase separation. Following embedding into oligo(poly[ethylene glycol] fumarate) hydrogel, the composite system showed prolonged and pH-responsive release of DOX. In vitro cytotoxicity study using osteosarcoma 143B cells showed substantial long-term cytotoxic effects for up to 30 days. As a result, the DOX drug delivery hydrogel developed in this work may have significant potential as a long-term and localized chemotherapy device that would be sensitive to the acidic microenvironment of osteosarcoma and other cancers. Impact Statement A composite hydrogel embedded with porous microspheres fabricated by phase separation methods was developed and showed excellent long-term anticancer drug delivery capability to cancer cells.

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.

Biomimetic biomaterials require good biocompatibility and bioactivity to serve as appropriate scaffolds for tissue engineering applications.