Liu, Xifeng

AbstractA promising new strategy emerged in bone tissue engineering is to incorporate black phosphorus (BP) into polymer scaffolds, fabricating nanocomposite hydrogel platforms with biocompatibility, degradation controllability, and osteogenic capacity. BP quantum dot is a new concept and stands out recently among the BP family due to its tiny structure and a series of excellent characteristics. In this study, BP was processed into nanosheets of three different sizes via different exfoliation strategies and then incorporated into cross‐linkable oligo[poly(ethylene glycol) fumarate] (OPF) to produce nanocomposite hydrogels for bone regeneration. The three different BP nanosheets were designated as BP‐L, BP‐M, and BP‐S, with a corresponding diameter of 242.3 ± 90.0, 107.1 ± 47.9, and 18.8 ± 4.6 nm. The degradation kinetics and osteogenic capacity of MC3T3 pre‐osteoblasts in vitro were both dependent on the BP size. BP exhibited a controllable degradation rate, which increased with the decrease of the size of the nanosheets, coupled with the release of phosphate in vitro. The osteogenic capacity of the hydrogels was promoted with the addition of all BP nanosheets, compared with OPF hydrogel alone. The smallest BP quantum dots was shown to be optimal in enhancing MC3T3 cell behaviors, including spreading, distribution, proliferation, and differentiation on the OPF hydrogels. These results reinforced that the supplementation of BP quantum dots into OPF nanocomposite hydrogel scaffolds could potentially find application in the restoration of bone defects.

In situ cell recruitment is a promising regenerative medicine strategy with the purpose of tissue regeneration without stem cell transplantation. This chemotaxis-based strategy is aimed at ensuring a restorative environment through the release of chemokines that promote site-specific migration of healing cell populations. Stromal cell-derived factor-1α (SDF-1α) is a critical chemokine that can regulate the migration of mesenchymal stem cells (MSCs). Accordingly, here, SDF-1α-loaded microporous oligo[poly(ethylene glycol) fumarate]/bis[2-(methacryloyloxy)ethyl] phosphate composites (SDF-1α/OPF/BP) were engineered and probed. SDF-1α/OPF/BP composites were loaded with escalating SDF-1α concentrations, namely, 0 ng/ml, 50 ng/ml, 100 ng/ml, and 200 ng/ml, and were cocultured with MSC. Scratching assay, Transwell assay, and three-dimensional migration model were utilized to assess the migration response of MSCs. Immunofluorescence staining of Runx2 and osteopontin (OPN), ELISA assay of osteocalcin (OCN) and alkaline phosphatase (ALP), and Alizarin Red S staining were conducted to assess the osteogenesis of MSCs. All SDF-1α/OPF/BP composites engendered a release of SDF-1α (>80%) during the first four days. SDF-1α released from the composites significantly promoted migration and osteogenic differentiation of MSCs documented by upregulated expression of osteogenic-related proteins, ALP, Runx2, OCN, and OPN. SDF-1α at 100 ng/ml was optimal for enhanced migration and osteogenic proficiency. Thus, designed SDF-1α/OPF/BP composites were competent in promoting the homing and osteogenesis of MSCs and thus offer a promising bioactive scaffold candidate for on-demand bone tissue regeneration.

AbstractA promising strategy that emerged in tissue engineering is to incorporate two‐dimensional (2D) materials into polymer scaffolds, producing materials with desirable mechanical properties and surface chemistries, which also display broad biocompatibility. Black phosphorus (BP) is a 2D material that has sparked recent scientific interest due to its unique structure and electrochemical characteristics. In this study, BP nanosheets (BPNSs) were incorporated into a cross‐linkable oligo[poly(ethylene glycol) fumarate] (OPF) hydrogel to produce a new nanocomposite for bone regeneration. BPNSs exhibited a controllable degradation rate coupled with the release of phosphate in vitro. MTS assay results together with live/dead images confirmed that the introduction of BPNSs into OPF hydrogels enhanced MC3T3‐E1 cell proliferation. Moreover, the morphology parameters indicated better attachments of cells in the BPNSs containing group. Immunofluorescence images as well as intercellular ALP and OCN activities showed that adding a certain amount of BPNSs to OPF hydrogel could greatly improve differentiation of pre‐osteoblasts on the hydrogel. Additionally, embedding black phosphorous into a neutral polymer network helped to control its cytotoxicity, with optimal cell growth observed at BP concentrations as high as 500 ppm. These results reinforced that the supplementation of OPF with BPNSs can increase the osteogenic capacity of polymer scaffolds for use in bone tissue engineering.

This review extensively summarized the properties and synthesis methods for phosphorene nanosheets, quantum dots, nanoribbons and their most-recent biomedical applications in bone, nerve, skin, brain, kidney, biosensor, and cancer related fields.

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.

AbstractConduits that promote nerve regeneration are currently of great medical concern, particularly when gaps exist between nerve endings. To address this issue, our laboratory previously developed a nerve conduit from biodegradable poly(caprolactone fumarate) (PCLF) that supports peripheral nerve regeneration. The present study improves upon this work by further developing an electrically conductive, positively charged PCLF scaffold through the incorporation of graphene, carbon nanotubes (CNTs), and [2‐(methacryloyloxy)ethyl]trimethylammonium chloride (MTAC) (PCLF–Graphene–CNT–MTAC) using ultraviolet (UV) induced photocrosslinking. Scanning electron microscopy, transmission electron microscopy, and atomic force microscopy were used to assess the incorporation of CNTs and graphene into PCLF–Graphene–CNT–MTAC scaffolds, which displayed enhanced surface roughness and reduced electrochemical impedance when compared to neat PCLF. Scaffolds with these surface modifications also showed improved growth and differentiation of rat pheochromocytoma 12 cells in vitro, with enhanced cell growth, neurite extension, and cellular migration. Furthermore, an increased number of neurite protrusions were observed when the conduit was electrically stimulated. These results show that the electrically conductive PCLF–Graphene–CNT–MTAC nerve scaffolds presented here support the cellular behaviors that are critical for nerve regeneration, ultimately making this material an attractive candidate for regenerative medicine applications.

Abstract3D bioprinting is a promising new tissue restoration technique that enables the precise deposition of cells and growth factors in order to more closely mimic the structure and function of native organs. In this study, we report the development of a new bioink using oligo(poly[ethylene glycol] fumarate) (OPF), a photo‐crosslinkable, and biodegradable polymer, for 3D bioprinting. In addition to OPF, a small portion of gelatin was also incorporated into the bioink to make it bio‐printable. After immersion in the cell medium, gelatin was eluted away to create a bioprinted scaffold of pure OPF. Excellent cell viability, spreading, and long‐term proliferation of encapsulated cells was observed using both bone and nerve cells as examples. These results demonstrate that OPF bioink has great potential in future 3D bioprinting applications that aim to replicate complex, layered tissues, and/or organs.