Mechanical properties, corrosion behavior, and in vitro and in vivo biocompatibility of hot-extruded Zn-5RE (RE = Y, Ho, and Er) alloys for biodegradable bone-fixation applications.

Biodegradable Zn alloys have significant application potential for hard-tissue implantation devices owing to their suitable degradation behavior and favorable biocompatibility. Nonetheless, pure Zn and its alloys in the as-cast state are mechanically instable and low in strength, which restricts their clinical applicability. Here, we report the exceptional mechanical, corrosion, and biocompatibility properties of hot-extruded Zn-5RE (wt.%, RE = rare earth of Y; or Ho; or Er) alloys intended for use in biodegradable bone substitutes. The microstructural characteristics, mechanical behavior, corrosion resistance, cytocompatibility, osteogenic differentiation, and capacity of osteogenesis in vivo of the Zn-5RE alloys are comparatively investigated. The Zn-5Y alloy demonstrates the best tensile properties, encompassing a 138 MPa tensile yield strength, a 302 MPa ultimate tensile strength, and 63% elongation, while the Zn-5Ho alloy shows the highest compression yield strength of 260 MPa and Vickers hardness of 104 HV. The Zn-5Er alloy shows a 126 MPa tensile yield strength, a 279 MPa ultimate tensile strength, 52% elongation, a 196 MPa compression yield strength, and a 101 HV Vickers microhardness. Further, the Zn-5Er alloy has a 130 µm per year corrosion rate in electrochemical tests and a 26 µm per year degradation rate in immersion tests, which is the lowest among the tested alloys. It also has the best in vitro osteogenic differentiation ability and capacity for osteogenesis and osteointegration in vivo after implantation in rat femurs among the Zn-5RE alloys, indicating promising potential in load-bearing biodegradable internal bone-fixation applications. STATEMENT OF SIGNIFICANCE: This work reports the exceptional mechanical, corrosion, and biocompatibility properties of hot-extruded (HE) Zn-5 wt.%-rare earth (Zn-5RE) alloys using single yttrium (Y), holmium (Ho), and erbium (Er) alloying for biodegradable bone-implant applications. Our findings demonstrate that the HE Zn-5Er alloy showed σuts of 279 MPa, tensile yield strength of 126 MPa, elongation of 51.6%, compression yield strength of 196 MPa, and microhardness of 101.2 HV. Further, HE Zn-5Er showed the lowest electrochemical corrosion rate of 130 µm/y and lowest degradation rate of 26 µm/y, and the highest in vitro osteogenic differentiation ability, in vivo osteogenesis, and osteointegration ability after implantation in rat femurs among the Zn-5RE alloys, indicating promising potential in load-bearing biodegradable internal bone-fixation applications.

Parathyroid hormone enhances the therapeutic effect of mesenchymal stem cells on temporomandibular joint osteoarthritis in rats.

OBJECTIVES: Temporomandibular joint osteoarthritis (TMJOA) is a degenerative disease affecting the joint, which is characterized by injury to the articular cartilage, as well as changes in the synovial and subchondral bone. TMJOA has a high incidence rate, without any effective treatment. Despite the therapeutic potential of mesenchymal stem cells (MSCs) in various diseases, their efficacy in treating TMJOA is constrained by the local hypoxic conditions and elevated reactive oxygen species (ROS) environment within the damaged temporomandibular joint. In recent years, many studies have reported that parathyroid hormone (PTH) can effectively treat TMJOA, and has an important impact on MSC differentiation. Therefore, we hypothesized that PTH may influence the potential of MSCs, thereby improving their therapeutic effect on TMJOA. METHODS: First, we isolated and cultured rat bone marrow MSCs, and evaluated their proliferation and differentiation after adding PTH. Next, the in vitro environment of hypoxia and high ROS was established by hypoxia condition and H2O2 treatment, and the resistance of PTH-treated MSCs to hypoxia and ROS was subsequently investigated. Finally, PTH-treated MSCs were used to treat TMJOA in a rat model to evaluate the efficacy of PTH. RESULTS: PTH enhanced the proliferation ability of MSCs, promoted the osteogenic differentiation of MSCs, and improved the tolerance of MSCs to hypoxia and ROS. Finally, the therapeutic effect of PTH-treated MSCs on TMJOA was significantly improved. CONCLUSION: PTH enhances the therapeutic effect of MSCs on TMJOA in rats.

Comparison Between Cancellous Trabecular and Cortical Specimens from Human Lumbar Spine Samples as an Alternative Source of Mesenchymal Stromal Cells.

Due to their immunosuppressive potential and ability to differentiate into multiple musculoskeletal cell lineages, mesenchymal stromal cells (MSCs) became popular in clinical trials for the treatment of musculoskeletal disorders. The aim of this study was to isolate and characterize native populations of MSCs from human cortical and cancellous bone from the posterior elements of the lumbar spine and determine what source of MSCs yields better quality and quantity of cells to be potentially used for spinal fusion repair. We were able to show that MSCs from trabecular and cortical spine had the typical MSC morphology and expression markers; the ability to differentiate in adipocyte, chondrocyte, or osteoblast but they did not have a consistent pattern in the expression of the specific differentiation lineage genes. Moreover, MSCs from both sites demonstrated an immune suppression profile suggesting that these cells may have a more promising success in applications related to immunomodulation more than exploring their ability to drive osteogenesis to prevent nonunion in spine fusion procedures.

The application of umbilical cord-derived MSCs in cardiovascular diseases.

Transplantation of stem cells is a promising, emerging treatment for cardiovascular diseases in the modern era. Mesenchymal stem cells (MSCs) derived from the umbilical cord are one of the most promising cell sources because of their capacity for differentiation into cardiomyocytes, endothelial cells and vascular smooth muscle cells in vitro/in vivo. In addition, umbilical cord-derived MSCs (UC-MSCs) secrete many effective molecules regulating apoptosis, fibrosis and neovascularization. Another important and specific characteristic of UC-MSCs is their low immunogenicity and immunomodulatory properties. However, the application of UC-MSCs still faces some challenges, such as low survivability and tissue retention in a harmful disease environment. Gene engineering and pharmacological studies have been implemented to overcome these difficulties. In this review, we summarize the differentiation ability, secretion function, immunoregulatory properties and preclinical/clinical studies of UC-MSCs, highlighting the advantages of UC-MSCs for the treatment of cardiovascular diseases.

Lactoferrin-Anchored Tannylated Mesoporous Silica Nanomaterials for Enhanced Osteo-Differentiation Ability.

In the present study, we created lactoferrin-anchored mesoporous silica nanomaterials with absorbed tannic acid (LF/TA-MSNs) and evaluated the effect of these LF/TA-MSNs on the in vitro osteo-differentiation ability of adipose-derived stem cells (ADSCs) by testing alkaline phosphatase (ALP) level, calcium accumulation, and expression of osteo-differentiation-specific genes, including osteocalcin (OCN) and osteopontin (OPN). Both bare MSNs and LF/TA-MSNs exhibited round nano-particle structures. The LF/TA-MSNs demonstrated prolonged LF release for up to 28 days. Treatment of ADSCs with LF (50 µg)/TA-MSNs resulted in markedly higher ALP level and calcium accumulation compared to treatment with LF (10 µg)/TA-MSNs or bare MSNs. Furthermore, LF (50 µg)/TA-MSNs remarkably increased mRNA levels of osteo-differentiation-specific genes, including OCN and OPN, compared to MSNs or LF (10 µg)/TA-MSNs. Together, these data suggest that the ability of LF/TA-MSNs to enhance osteo-differentiation of ADSCs make them a possible nanovehicle for bone healing and bone regeneration in patients with bone defect or disease.

Different culture method changing CD105 expression in amniotic fluid MSCs without affecting differentiation ability or immune function.

MSCs are kind of cultured cells that reside in different tissues as inducers or regulators of physiological and pathological processes. Here, we derived MSCs from amniotic fluid and compared their differentiation ability and immunosuppression effect on PHA-activated PBMC with those of MSCs isolated from umbilical cords. Amniotic fluid MSCs were isolated and cultured on commercial AFC medium and classic MSC medium, and the number and size of colonies were used to evaluate differences in primary and passaged culture. Rate of proliferation, population doubling time, cell morphology, cell surface markers and mRNA expression were measured in subcultured cells. Furthermore, a comparative study was performed with umbilical cord MSCs to assess the ability of differentiation and immunosuppressive effect of PHA-stimulated PBMCs. Amniotic fluid MSCs were isolated and expanded by three methods, and exhibited nearly all the characteristics of umbilical cord MSCs. Compared with umbilical cord MSCs, amniotic fluid MSCs had an enhanced osteogenic and chrondrogenic differentiation capability, and stronger immunosuppression effect of inhibition of PHA-activated PBMC division. Culture with commercial AFCs medium yielded the highest percentage of CD105 expression and showed some advantages in primary cell isolation, cell source-specific marker retention and cell proliferation. We demonstrated that amniotic fluid MSCs exhibited some advantages over umbilical cord MSCs, and different culture media caused cell proliferation, cell surface marker and cell morphology change, but were not associated with varying differentiation capability and immune effects.