Enzyme-controlled, nutritive hydrogel for mesenchymal stromal cell survival and paracrine functions.

Culture-adapted human mesenchymal stromal cells (hMSCs) are appealing candidates for regenerative medicine applications. However, these cells implanted in lesions as single cells or tissue constructs encounter an ischemic microenvironment responsible for their massive death post-transplantation, a major roadblock to successful clinical therapies. We hereby propose a paradigm shift for enhancing hMSC survival by designing, developing, and testing an enzyme-controlled, nutritive hydrogel with an inbuilt glucose delivery system for the first time.

Glucose depletion decreases cell viability without triggering degenerative changes in a physiological nucleus pulposus explant model.

Although the etiology of intervertebral disc degeneration is still unresolved, the nutrient paucity resulting from its avascular nature is suspected of triggering degenerative processes in its core: the nucleus pulposus (NP). While severe hypoxia has no significant effects on NP cells, the impact of glucose depletion, such as found in degenerated discs (0.2-1 mM), is still uncertain.

Glucose Metabolism: Optimizing Regenerative Functionalities of Mesenchymal Stromal Cells Postimplantation.

Mesenchymal stromal cells (MSCs) are considered promising candidates for regenerative medicine applications. Their clinical performance postimplantation, however, has been disappointing. This lack of therapeutic efficacy is most likely due to suboptimal formulations of MSC-containing material constructs.

Targeted resequencing of the 13q13 spondyloarthritis-linked locus identifies a rare variant in FREM2 possibly associated with familial spondyloarthritis.

Objectives: The strong heritability of spondyloarthritis remains poorly explained, despite several large-scale association studies. A recent linkage analysis identified a new region linked to SpA on 13q13. Here we searched for variants potentially explaining this linkage signal by deep-sequencing of the region.

Three-dimensional Printing of Biomimetic Titanium Mimicking Trabecular Bone Induces Human Mesenchymal Stem Cell Proliferation: An In-vitro Analysis.

Study Design: In vitro analysis.

Objective: The aim of this study was to assess the effect of three-dimensional (3D) printing of porous titanium on human mesenchymal stem cell (hMSC) adhesion, proliferation, and osteogenic differentiation.

Summary Of Background Data: A proprietary implant using three-dimensional porous titanium (3D-pTi) that mimics trabecu-lar bone structure, roughness, porosity, and modulus of elasticity was created (Ti-LIFE technology™, Spineart SA Switzerland).

Osteoformation potential of an allogenic partially demineralized bone matrix in critical-size defects in the rat calvarium.

Allogenic demineralized bone matrix has been developed as a reliable alternative to the autologous bone graft. In the present study, we assessed the osteoformation potential of a partially demineralized bone matrix (PDBM) in a paste form obtained without an added carrier. This formulation included the preparation of cancelous bone from femoral heads after decellularision, delipidation, demineralization in HCl and autoclaving at 121 °C.

In Vivo bone tissue induction by freeze-dried collagen-nanohydroxyapatite matrix loaded with BMP2/NS1 mRNAs lipopolyplexes.

Messenger RNA (mRNA) activated matrices (RAMs) are interesting to orchestrate tissue and organ regeneration due to the in-situ and sustained production of functional proteins. However, the immunogenicity of in vitro transcribed mRNA and the paucity of proper in vivo mRNA delivery vector need to be overcome to exert the therapeutic potential of RAM. We developed a dual mRNAs system for in vitro osteogenesis by co-delivering NS1 mRNA with BMP2 mRNA to inhibit RNA sensors and enhance BMP-2 expression.

Experimental Type 2 Diabetes Differently Impacts on the Select Functions of Bone Marrow-Derived Multipotent Stromal Cells.

Bone marrow-derived multipotent stromal cells (BMMSCs) represent an attractive therapeutic modality for cell therapy in type 2 diabetes mellitus (T2DM)-associated complications. T2DM changes the bone marrow environment; however, its effects on BMMSC properties remain unclear. The present study aimed at investigating select functions and differentiation of BMMSCs harvested from the T2DM microenvironment as potential candidates for regenerative medicine.

Osteogenic-differentiated mesenchymal stem cell-secreted extracellular matrix as a bone morphogenetic protein-2 delivery system for ectopic bone formation.

While human bone morphogenetic protein-2 (BMP-2) is a promising growth factor for bone regeneration, a major challenge in biomedical applications is finding an optimal carrier for its delivery at the site of injury. Because of their natural affinities for growth factors (including BMP-2) as well as their role in instructing cell function, cultured cell-derived extracellular matrices (ECM) are of special interest. We hereby hypothesized that a "bony matrix" containing mineralized, osteogenic ECM is a potential efficacious carrier of BMP-2 for promoting bone formation and, therefore, compared the efficacy of the decellularized ECM derived from osteogenic-differentiated human mesenchymal stem cells (hMSCs) to the one obtained from ECM from undifferentiated hMSCs.

Use of supercritical carbon dioxide technology for fabricating a tissue engineering scaffold for anterior cruciate ligament repair.

Tissue-engineered grafts may be useful in Anterior Cruciate Ligament (ACL) repair and provide a novel, alternative treatment to clinical complications of rupture, harvest site morbidity and biocompatibility associated with autografts, allografts and synthetic grafts. We successfully used supercritical carbon dioxide (Sc-CO) technology for manufacturing a "smart" biomaterial scaffold, which retains the native protein conformation and tensile strength of the natural ACL but is decellularized for a decreased immunogenic response. We designed and fabricated a new scaffold exhibiting (1) high tensile strength and biomechanical properties comparable to those of the native tissue, (2) thermodynamically-stable extra-cellular matrix (ECM), (3) preserved collagen composition and crosslinking, (4) a decellularized material milieu with potential for future engineering applications and (5) proven feasibility and biocompatibility in an animal model of ligament reconstruction.

Impact of Astaxanthin on Diabetes Pathogenesis and Chronic Complications.

Oxidative stress (OS) plays a pivotal role in diabetes mellitus (DM) onset, progression, and chronic complications. Hyperglycemia-induced reactive oxygen species (ROS) have been shown to reduce insulin secretion from pancreatic β-cells, to impair insulin sensitivity and signaling in insulin-responsive tissues, and to alter endothelial cells function in both type 1 and type 2 DM. As a powerful antioxidant without side effects, astaxanthin (ASX), a xanthophyll carotenoid, has been suggested to contribute to the prevention and treatment of DM-associated pathologies.

Co-delivery of NS1 and BMP2 mRNAs to murine pluripotent stem cells leads to enhanced BMP-2 expression and osteogenic differentiation.

Application of messenger RNA (mRNA) for bone regeneration is a promising alternative to DNA, recombinant proteins and peptides. However, exogenous in vitro transcribed mRNA (IVT mRNA) triggers innate immune response resulting in mRNA degradation and translation inhibition. Inspired by the ability of viral immune evasion proteins to inhibit host cell responses against viral RNA, we applied non-structural protein-1 (NS1) from Influenza A virus (A/Texas/36/1991) as an IVT mRNA enhancer.

Custom-made macroporous bioceramic implants based on triply-periodic minimal surfaces for bone defects in load-bearing sites.

The architectural features of synthetic bone grafts are key parameters for regulating cell functions and tissue formation for the successful repair of bone defects. In this regard, macroporous structures based on triply-periodic minimal surfaces (TPMS) are considered to have untapped potential. In the present study, custom-made implants based on a gyroid structure, with (GPRC) and without (GP) a cortical-like reinforcement, were specifically designed to fit an intended bone defect in rat femurs.

Correction to: Induced membrane maintains its osteogenic properties even when the second stage of Masquelet's technique is performed later.

The original version of this article unfortunately contained a mistake. The presentation and legends of Figs. 4 and 5 were incorrect.

Understanding and leveraging cell metabolism to enhance mesenchymal stem cell transplantation survival in tissue engineering and regenerative medicine applications.

In tissue engineering and regenerative medicine, stem cell-specifically, mesenchymal stromal/stem cells (MSCs)-therapies have fallen short of their initial promise and hype. The observed marginal, to no benefit, success in several applications has been attributed primarily to poor cell survival and engraftment at transplantation sites. MSCs have a metabolism that is flexible enough to enable them to fulfill their various cellular functions and remarkably sensitive to different cellular and environmental cues.

Induced membrane maintains its osteogenic properties even when the second stage of Masquelet's technique is performed later.

Purpose: Previous clinical studies have shown the effectiveness of bone repair using two-stage surgery called the induced membrane (IM) technique. The optimal wait before the second surgery is said to be 1 month. We have been successfully performing the IM technique while waiting an average of 6 months to carry out the second stage.

The paracrine effects of human induced pluripotent stem cells promote bone-like structures via the upregulation of BMP expression in a mouse ectopic model.

Use of human induced pluripotent stem cells (h-iPSCs) for bone tissue engineering is most appealing, because h-iPSCs are an inexhaustible source of osteocompetent cells. The present study investigated the contribution of undifferentiated h-iPSCs and elucidated aspects of the underlying mechanism(s) of the involvement of these cells to new bone formation. Implantation of undifferentiated h-iPSCs seeded on coral particles in ectopic sites of mice resulted in expression of osteocalcin and DMP-1, and in mineral content similar to that of the murine bone.

Effect of the Bone Morphogenetic Protein-2 Doses on the Osteogenic Potential of Human Multipotent Stromal Cells- Containing Tissue Engineered Constructs.

A strategy for improving the efficacy of stem cell-based bone tissue engineering (TE) constructs is to combine bone morphogenetic protein-2 (BMP-2) with multipotent stromal cells (MSC). Previous studies on the potential cooperative effect of BMP-2 with human multipotent stromal cells (hMSCs) on bone formation have, however, shown contradictory results likely due to the various and/or inappropriate BMP-2 doses. Our results provided evidence that the addition of BMP-2 at low dose only was beneficial to improve the osteogenic potential of hMSCs-containing TE constructs, whereas BMP-2 delivered at high dose overcame the advantage of combining this growth factor with hMSCs.

Feasibility of Bioengineered Tracheal and Bronchial Reconstruction Using Stented Aortic Matrices.

Importance: Airway transplantation could be an option for patients with proximal lung tumor or with end-stage tracheobronchial disease. New methods for airway transplantation remain highly controversial.

Objective: To establish the feasibility of airway bioengineering using a technique based on the implantation of stented aortic matrices.

Type 2 diabetes impairs angiogenesis and osteogenesis in calvarial defects: MicroCT study in ZDF rats.

Objectives: The present study was motivated by the fact that bone regeneration in the compromised vascular microenvironment of T2DM is challenging and the factors that determine the adverse bone regeneration outcomes are poorly understood. For this purpose the effect of T2DM on osteogenic and angiogenic healing potential of calvarial bone, was evaluated in Zucker diabetic fatty (ZDF) rats, an established rat model for obese T2DM.

Materials And Methods: The study used 16-week-old ZDF rats and their age-matched controls, Zucker Lean (ZL).

Traumatic leaflet injury: comparison of porcine leaflet self-expandable and bovine leaflet balloon-expandable prostheses.

Objectives: The main goal of this study was to compare the occurrence of post-deployment leaflet injury between prostheses made of porcine and bovine pericardium.

Methods: Two types of prostheses, self-expandable prostheses with porcine pericardial leaflet on one side and balloon-expandable prostheses with bovine pericardial leaflet on the other side, were used. In each group, crimped prostheses were compared with control non-crimped prostheses.

Osteogenic potential of adipogenic predifferentiated human bone marrow-derived multipotent stromal cells for bone tissue-engineering.

In the present study, we evaluated the benefits of an adipogenic predifferentiation, the pathway most closely related to osteoblastogenesis, on the pro-osteogenic potential of human adult multipotent bone marrow stromal cells (hBMSCs), both in vitro and in vivo. Adipogenic differentiation of hBMSCs for 14 days resulted in a heterogeneous cell population from which the most adipogenic-committed cells were eliminated by their lack of readhesion ability. Our results provided evidence that the select adherent adipogenic differentiated hBMSCs (sAD+ cells) express a gene profile characteristic of both adipogenic and osteogenic lineages.

In vivo evaluation of the bone integration of coated poly(vinyl-alcohol) hydrogel fiber implants.

Recently, it has been shown that constructs of poly(vinyl alcohol) (PVA) hydrogel fibers reproduce closely the tensile behavior of ligaments. However, the biological response to these systems has not been explored yet. Here, we report the first in vivo evaluation of these implants and focus on the integration in bone, using a rabbit model of bone tunnel healing.