Impact of Sulfated Hyaluronan on Bone Metabolism in Diabetic Charcot Neuroarthropathy and Degenerative Arthritis.

Bone in diabetes mellitus is characterized by an altered microarchitecture caused by abnormal metabolism of bone cells. Together with diabetic neuropathy, this is associated with serious complications including impaired bone healing culminating in complicated fractures and dislocations, especially in the lower extremities, so-called Charcot neuroarthropathy (CN). The underlying mechanisms are not yet fully understood, and treatment of CN is challenging.

Sulfated glycosaminoglycans inhibit transglutaminase 2 by stabilizing its closed conformation.

Transglutaminases (TGs) catalyze the covalent crosslinking of proteins via isopeptide bonds. The most prominent isoform, TG2, is associated with physiological processes such as extracellular matrix (ECM) stabilization and plays a crucial role in the pathogenesis of e.g.

Hyaluronan/Collagen Hydrogels with Sulfated Glycosaminoglycans Maintain VEGF Activity and Fine-Tune Endothelial Cell Response.

In order to restore the regeneration capacity of large-size vascularized tissue defects, innovative biomaterial concepts are required. Vascular endothelial growth factor (VEGF) is a key factor of angiogenesis interacting with sulfated glycosaminoglycans (sGAG) within the extracellular matrix. As this interplay mainly controls and directs the biological activity of VEGF, we used chemically modified sGAG derivatives to evaluate the structural requirements of sGAG for controlling and tuning VEGF function and to translate these findings into the design of biomaterials.

Heparin Enriched-WPI Coating on Ti6Al4V Increases Hydrophilicity and Improves Proliferation and Differentiation of Human Bone Marrow Stromal Cells.

Titanium alloy (Ti6Al4V) is one of the most prominent biomaterials for bone contact because of its ability to bear mechanical loading and resist corrosion. The success of Ti6Al4V implants depends on bone formation on the implant surface. Hence, implant coatings which promote adhesion, proliferation and differentiation of bone-forming cells are desirable.

Identification of intracellular glycosaminoglycan-interacting proteins by affinity purification mass spectrometry.

Glycosaminoglycans (GAGs) are essential functional components of the extracellular matrix (ECM). Artificial GAGs like sulfated hyaluronan (sHA) exhibit pro-osteogenic properties and boost healing processes. Hence, they are of high interest for supporting bone regeneration and wound healing.

Impact of binding mode of low-sulfated hyaluronan to 3D collagen matrices on its osteoinductive effect for human bone marrow stromal cells.

Synthetically sulfated hyaluronan derivatives were shown to facilitate osteogenic differentiation of human bone marrow stromal cells (hBMSC) by application in solution or incorporated in thin collagen-based coatings. In the presented study, using a biomimetic three-dimensional (3D) cell culture model based on fibrillary collagen I (3D Col matrix), we asked on the impact of binding mode of low sulfated hyaluronan (sHA) in terms of adsorptive and covalent binding on osteogenic differentiation of hBMSC. Both binding modes of sHA induced osteogenic differentiation.

Rolled-Up Metal Oxide Microscaffolds to Study Early Bone Formation at Single Cell Resolution.

Titanium and its alloys are frequently used to replace structural components of the human body due to their high mechanical strength, low stiffness, and biocompatibility. In particular, the use of porous materials has improved implant stabilization and the promotion of bone. However, it remains unclear which material properties and geometrical cues are optimal for a proper osteoinduction and osseointegration.

Remodeling of Three-Dimensional Collagen I Matrices by Human Bone Marrow Stromal Cells during Osteogenic Differentiation .

Cell fate is triggered by the characteristics of the surrounding extracellular matrix (ECM) including its composition and topological and mechanical properties. Human bone marrow stromal cells (hBMSC) are known to reside in a niche environment where they are maintained in a quiescent, multipotent state, also controlled by the ECM characteristics. In this study, three-dimensional (3D) fibrillary collagen I (Col)-based matrices with defined topological and mechanical characteristics were used (pore size of 3-4 μm, fibril diameter of ∼0.

Dairy-Inspired Coatings for Bone Implants from Whey Protein Isolate-Derived Self-Assembled Fibrils.

To improve the integration of a biomaterial with surrounding tissue, its surface properties may be modified by adsorption of biomacromolecules, e.g., fibrils.

Biological Cell Investigation of Structured Nitinol Surfaces for the Functionalization of Implants.

Expandable implants including shape memory alloy (SMA) elements have great potential to minimize the risk of implant loosening and to increase the primary stability of bone anchoring. Surface structuring of such elements may further improve these properties and support osteointegration and bone healing. In this given study, SMA sheets were processed by deploying additive and removal manufacturing technologies for 3D-printed surgical implants.

Glycosaminoglycans influence enzyme activity of MMP2 and MMP2/TIMP3 complex formation - Insights at cellular and molecular level.

The extracellular matrix (ECM) is a highly dynamic network constantly remodeled by a fine-tuned protein formation and degradation balance. Matrix metalloproteinases (MMPs) constitute key orchestrators of ECM degradation. Their activity is controlled by tissue inhibitors of metalloproteinases (TIMPs) and glycosaminoglycans (GAG).

Loss of Stromal Galectin-1 Enhances Multiple Myeloma Development: Emphasis on a Role in Osteoclasts.

Multiple myeloma osteolytic disease is caused by an uncoupled bone-remodelling process with an increased osteoclast activity. Disease development relies on interactions between myeloma cells and bone marrow stromal cells. Recent findings suggest a role for glycan-binding proteins in myeloma microenvironment.

Sulfated hyaluronic acid and dexamethasone possess a synergistic potential in the differentiation of osteoblasts from human bone marrow stromal cells.

The development of novel bioactive biomaterials is urgently needed to meet the needs of an aging population. Both sulfated hyaluronic acid and dexamethasone are candidates for the functionalization of bone grafts, as they have been shown to enhance the differentiation of osteoblasts from bone marrow stromal cells in vitro and in vivo. However, the underlying mechanisms are not fully understood.

Maternal embryonic leucine zipper kinase inhibitor OTSSP167 has preclinical activity in multiple myeloma bone disease.

Multiple myeloma bone disease is characterized by an uncoupling of bone remodeling in the multiple myeloma microenvironment, resulting in the development of lytic bone lesions. Most myeloma patients suffer from these bone lesions, which not only cause morbidity but also negatively impact survival. The development of novel therapies, ideally with a combined anti-resorptive and bone-anabolic effect, is of great interest because lesions persist with the current standard of care, even in patients in complete remission.

IL-6, IL-1β, and TNF-α only in combination influence the osteoporotic phenotype in Crohn's patients via bone formation and bone resorption.

Background: Crohn´s disease (CD) is associated with a higher prevalence of osteoporosis. The pathogenesis of bone affliction remains controversial, especially if inflammatory cytokines or glucocorticoid therapy are the main contributors. In postmenopausal osteoporosis, bone resorption is induced by IL-6, IL-1β and TNF-α.

Adhesive Drug Delivery Systems Based on Polyelectrolyte Complex Nanoparticles (PEC NP) for Bone Healing.

Background: In this contribution an overview is given on own work concerning drug loaded Polyelectrolyte Complex (PEC) Nanoparticles (NP) used to functionalize Bone Substitute Materials (BSM) for the therapy of bone defects associated with systemic bone diseases. In this context, drug loaded PEC NP have certain advantages, which are exemplarily summarized herein.

Methods: Concerning preparative methods PEC NP were fabricated by controlled mixing of polycation and polyanion solutions and integration of charged drugs during and after mixing.

Metal release and cell biological compatibility of beta-type Ti-40Nb containing indium.

Small indium (In) additions up to 5 wt % to the beta-type Ti-40Nb alloy effectively improve its mechanical biofunctionality. The impact on its biocompatibility is addressed in this work. Comparative electrochemical polarization studies and inductively coupled plasma optical emission spectrometry analyses were conducted in Tris-buffered saline (on the basis of 150 mM NaCl) with pH 7.

Hyaluronan/Collagen Hydrogels with Sulfated Hyaluronan for Improved Repair of Vascularized Tissue Tune the Binding of Proteins and Promote Endothelial Cell Growth.

Innovative biomaterial-based concepts are required to improve wound healing of damaged vascularized tissues especially in elderly multimorbid patients. To develop functional hydrogels as 3D cellular microenvironments and as carrier or scavenging systems, e.g.

A supplement-free osteoclast-osteoblast co-culture for pre-clinical application.

There is increasing demand for efficient and physiological in vitro cell culture systems suitable for testing new pharmaceutical drugs or for evaluating materials for tissue regeneration. In particular, co-cultures of two or more tissue-relevant cell types have the advantage to study the response of cells on diverse parameters in a more natural environment with respect to physiological complexity. We developed a direct bone cell co-culture system using human peripheral blood monocytes (hPBMC) and human bone marrow stromal cells (hBMSC) as osteoclast/osteoblast precursor cells, respectively, strictly avoiding external supplements for the induction of differentiation.

Sulfated Hyaluronan Derivatives Modulate TGF-β1:Receptor Complex Formation: Possible Consequences for TGF-β1 Signaling.

Glycosaminoglycans are known to bind biological mediators thereby modulating their biological activity. Sulfated hyaluronans (sHA) were reported to strongly interact with transforming growth factor (TGF)-β1 leading to impaired bioactivity in fibroblasts. The underlying mechanism is not fully elucidated yet.

Initial cell adhesion of three cell types in the presence and absence of serum proteins.

With the development of a wide range of new biomaterials for the sensing of different cell behaviour, it is important to consider whether the cells tested in vitro are in direct contact with the material or whether cell-biomaterial contact is mediated by an interfacial layer of proteins originating from the culture medium or from the cells themselves. Thus, this study describes the differences between the cell adhesion mediated by proteins originating from foetal bovine serum and without the presence of such proteins 2 h following cell seeding exemplarily with different cell types (an osteoblastic cell line, primary fibroblasts, and mesenchymal stem cells). Three of the examined cell types were found to react differently to differing conditions in terms of cell shape, area, and number.