Safety of an investigational formulation of budesonide (budesonide oral suspension) for eosinophilic oesophagitis: an integrated safety analysis of six phase 1-3 clinical trials.

Background: Questions remain regarding the safety of swallowed topical corticosteroids in eosinophilic oesophagitis (EoE).

Aim: To assess the safety of an investigational formulation of budesonide (budesonide oral suspension; BOS) from six trials.

Methods: Safety data were integrated from six trials (healthy adults: SHP621-101 [phase 1]; patients with EoE: MPI 101-01 and MPI 101-06 [phase 2]; SHP621-301, SHP621-302 and SHP621-303 [phase 3]) for participants who received ≥1 dose of study drug (BOS 2.

Rapid Response to Vedolizumab Therapy in Biologic-Naive Patients With Inflammatory Bowel Diseases.

Background & Aims: Vedolizumab, a humanized monoclonal antibody against α4β7 integrin, is used to treat adults with moderately to severely active ulcerative colitis (UC) and Crohn's disease (CD). We investigated the time course of clinical response to vedolizumab in patients who were and were not previously treated with tumor necrosis factor (TNF) antagonists.

Methods: We performed a post-hoc analysis of data from phase 3, randomized, controlled trials of vedolizumab vs placebo in adult patients with UC (N = 374) or CD (N = 784).

The importance of both fibroblasts and keratinocytes in a bilayered living cellular construct used in wound healing.

Cross talk between fibroblasts and keratinocytes, which maintains skin homeostasis, is disrupted in chronic wounds. For venous leg ulcers and diabetic foot ulcers, a bilayered living cellular construct (BLCC), containing both fibroblasts and keratinocytes that participate in cross talk, is a safe and effective product in healing chronic wounds. To show the importance of both cell types in BLCC, constructs were generated containing only fibroblasts or only keratinocytes and compared directly to BLCC via histology, mechanical testing, gene/protein analysis, and angiogenesis assays.

Nanofiber orientation and surface functionalization modulate human mesenchymal stem cell behavior in vitro.

Electrospun nanofiber meshes have emerged as a new generation of scaffold membranes possessing a number of features suitable for tissue regeneration. One of these features is the flexibility to modify their structure and composition to orchestrate specific cellular responses. In this study, we investigated the effects of nanofiber orientation and surface functionalization on human mesenchymal stem cell (hMSC) migration and osteogenic differentiation.

Runx2 overexpression in bone marrow stromal cells accelerates bone formation in critical-sized femoral defects.

The repair of large nonunions in long bones remains a significant clinical problem due to high failure rates and limited tissue availability for auto- and allografts. Many cell-based strategies for healing bone defects deliver bone marrow stromal cells (BMSCs) to the defect site to take advantage of the inherent osteogenic capacity of this cell type. However, many factors, including donor age and ex vivo expansion of the cells, cause BMSCs to lose their differentiation ability.

Coating of biomaterial scaffolds with the collagen-mimetic peptide GFOGER for bone defect repair.

Healing large bone defects and non-unions remains a significant clinical problem. Current treatments, consisting of auto and allografts, are limited by donor supply and morbidity, insufficient bioactivity and risk of infection. Biotherapeutics, including cells, genes and proteins, represent promising alternative therapies, but these strategies are limited by technical roadblocks to biotherapeutic delivery, cell sourcing, high cost, and regulatory hurdles.

Micro-CT based quantification of non-mineralized tissue on cultured hydroxyapatite scaffolds.

An improved method to determine material volumes from microcomputed tomography (micro-CT) data is presented. In particular, the method can account for materials with significantly overlapping peaks and small volumes. The example case is a hydroxyapatite scaffold cultured with osteoprogenitor cells.

Impaired angiogenesis, early callus formation, and late stage remodeling in fracture healing of osteopontin-deficient mice.

Unlabelled: OPN is an ECM protein with diverse localization and functionality. The role of OPN during fracture healing was examined using wildtype and OPN(-/-) mice. Results showed that OPN plays an important role in regulation of angiogenesis, callus formation, and mechanical strength in early stages of healing and facilitates late stage bone remodeling and ECM organization.

Effects of degradation and porosity on the load bearing properties of model hydroxyapatite bone scaffolds.

Degradation of three types of model hydroxyapatite (HA) scaffolds was studied after in vitro degradation in a sodium acetate buffer (pH 4). Degradation was evaluated using compression testing, scanning electron microscopy (SEM), inductively coupled plasma (ICP) analysis, and weight measurements. Scaffolds were fabricated with a solid freeform fabrication (SFF) technique based on the robotic deposition of colloidal pastes.

Glucocorticoid-induced osteogenesis is negatively regulated by Runx2/Cbfa1 serine phosphorylation.

Glucocorticoid hormones have complex stimulatory and inhibitory effects on skeletal metabolism. Endogenous glucocorticoid signaling is required for normal bone formation in vivo, and synthetic glucocorticoids, such as dexamethasone, promote osteoblastic differentiation in several in vitro model systems. The mechanism by which these hormones induce osteogenesis remains poorly understood.