Tenocytes of chronic rotator cuff tendon tears can be stimulated by platelet-released growth factors.

Background: Bone-to-tendon healing after rotator cuff repairs is mainly impaired by poor tissue quality. The tenocytes of chronic rotator cuff tendon tears are not able to synthesize normal fibrocartilaginous extracellular matrix (ECM). We hypothesized that in the presence of platelet-released growth factors (PRGF), tenocytes from chronically retracted rotator cuff tendons proliferate and synthesize the appropriate ECM proteins.

Homing of mesenchymal stem cells in induced degenerative intervertebral discs in a whole organ culture system.

Study Design: Homing of human bone marrow-derived mesenchymal stem cells (BMSCs) was studied using ex vivo cultured bovine caudal intervertebral discs (IVDs).

Objective: To investigate in a whole organ culture whether metabolic and mechanical challenges can induce BMSC recruitment into the IVD.

Summary Of Background Data: Cells from injured tissues release cytokines and mediators that enable the recruitment of progenitor cells.

Enhanced adenovirus transduction of hMSCs using 3D hydrogel cell carriers.

Hydrogels are increasingly being investigated as a means to implant cells for tissue engineering. One way to further enhance the repair response would be to combine the hydrogel cell carrier with gene transfer. Gene therapy, using adenoviral vectors, is an effective way to provide transient delivery of bioactive factors.

Sliding motion modulates stiffness and friction coefficient at the surface of tissue engineered cartilage.

Objective: Functional cartilage tissue engineering aims to generate grafts with a functional surface, similar to that of authentic cartilage. Bioreactors that stimulate cell-scaffold constructs by simulating natural joint movements hold great potential to generate cartilage with adequate surface properties. In this study two methods based on atomic force microscopy (AFM) were applied to obtain information about the quality of engineered graft surfaces.

Identification of cell surface-specific markers to target human nucleus pulposus cells: expression of carbonic anhydrase XII varies with age and degeneration.

Objective: Back pain is a major cause of disability, affecting millions of people worldwide. One cause of axial back pain is degeneration of the nucleus pulposus (NP) of the intervertebral disc. This study was undertaken to investigate associations of NP cells with cell surface-specific proteins that differ from proteins in closely related cell types, i.

Pinealectomy affects bone mineral density and structure--an experimental study in sheep.

Background: Osteoporosis and associated fractures are a major public health burden and there is great need for a large animal model. Melatonin, the hormone of the pineal gland, has been shown to influence bone metabolism. This study aims to evaluate whether absence of melatonin due to pinealectomy affects the bone mass, structure and remodeling in an ovine animal model.

A combination of shear and dynamic compression leads to mechanically induced chondrogenesis of human mesenchymal stem cells.

There is great interest in how bone marrow derived stem cells make fate decisions. Numerous studies have investigated the role of individual growth factors on mesenchymal stem cell differentiation, leading to protocols for cartilage, bone and adipose tissue. However, these protocols overlook the role of biomechanics on stem cell differentiation.

Injectable thermoreversible hyaluronan-based hydrogels for nucleus pulposus cell encapsulation.

Introduction: Thermoreversible hydrogels have potential in spine research as they provide easy injectability and mild gelling mechanism (by physical cross-link). The purpose of this study was to assess the potential of thermoreversible hyaluronan-based hydrogels (HA-pNIPAM) (pNIPAM Mn = 10, 20, 35 × 10(3) g mol(-1)) as nucleus pulposus cells (NPC) carrier.

Materials And Methods: Cytocompatibility (WST-1 assay), viability (trypan blue), morphology (toluidine blue), sulphated glycosaminoglycan synthesis (DMMB assay) and gene expression profile (real-time PCR) of bovine NPC cultured in HA-pNIPAM were followed for 1 week and compared to alginate gel bead cultures.

Evaluation of the in vitro cell-material interactions and in vivo osteo-integration of a spinal acrylic bone cement.

Introduction: Polymethylmethacrylate bone cements have proven performance in arthroplasty and represent a common bone filler, e.g. in vertebroplasty.

Role of hypoxia and growth and differentiation factor-5 on differentiation of human mesenchymal stem cells towards intervertebral nucleus pulposus-like cells.

There is evidence that mesenchymal stem cells (MSCs) can differentiate towards an intervertebral disc (IVD)-like phenotype. We compared the standard chondrogenic protocol using transforming growth factor beta-1 (TGFß) to the effects of hypoxia, growth and differentiation factor-5 (GDF5), and coculture with bovine nucleus pulposus cells (bNPC). The efficacy of molecules recently discovered as possible nucleus pulposus (NP) markers to differentiate between chondrogenic and IVD-like differentiation was evaluated.

Platelet released growth factors boost expansion of bone marrow derived CD34(+) and CD133(+) endothelial progenitor cells for autologous grafting.

Stem cell based autologous grafting has recently gained mayor interest in various surgical fields for the treatment of extensive tissue defects. CD34(+) and CD133(+) cells that can be isolated from the pool of bone marrow mononuclear cells (BMC) are capable of differentiating into mature endothelial cells in vivo. These endothelial progenitor cells (EPC) are believed to represent a major portion of the angiogenic regenerative cells that are released from bone marrow when tissue injury has occurred.

Physical stimulation of chondrogenic cells in vitro: a review.

Background: Mechanical stimuli are of crucial importance for the development and maintenance of articular cartilage. For conditioning of cartilaginous tissues, various bioreactor systems have been developed that have mainly aimed to produce cartilaginous grafts for tissue engineering applications. Emphasis has been on in vitro preconditioning, whereas the same devices could be used to attempt to predict the response of the cells in vivo or as a prescreening method before animal studies.

The role of retinoic acid receptor inhibitor LE135 on the osteochondral differentiation of human bone marrow mesenchymal stem cells.

The present study aimed to investigate the role of a retinoic acid receptor-β (RARβ) inhibitor LE135 on TGF-β induced chondrogenesis of human bone marrow mesenchymal stem cells (hMSCs). Pellet culture with exogenous transforming growth factor-β (TGF-β), and a mechanically loaded scaffold system were used to provide two culture models. All samples were cultured for 8 days and changes in early gene expression were determined.

An injectable vehicle for nucleus pulposus cell-based therapy.

An injectable hydrogel, acting as a reservoir for cell delivery and mimicking the native environment, offers promise for nucleus pulposus (NP) repair and regeneration. Herein, the potential of a stabilised type II collagen hydrogel using poly(ethylene glycol) ether tetrasuccinimidyl glutarate (4S-StarPEG) cross-linker, enriched with hyaluronic acid (HA) was investigated. The optimally stabilised type II collagen hydrogel was determined by assessing free amine groups, resistance to enzymatic degradation, gel point.

Platelet-released supernatant induces osteoblastic differentiation of human mesenchymal stem cells: potential role of BMP-2.

Platelet-rich preparations have recently gained popularity in maxillofacial and dental surgery, but their beneficial effect is still under debate. Furthermore, very little is known about the effect of platelet preparations at the cellular level, and the underlying mechanisms. In this study, we tested the effect of platelet-released supernatant (PRS) on human mesenchymal stem cell (MSC) differentiation towards an osteoblastic phenotype in vitro.

Promoting external inosculation of prevascularised tissue constructs by pre-cultivation in an angiogenic extracellular matrix.

The engineering of preformed microvessels offers the promising opportunity to rapidly vascularise implanted tissue constructs by the process of inosculation. Herein, we analyzed whether this process may further be accelerated by cultivation of prevascularised tissue constructs in Matrigel before implantation. Nano-size hydroxyapatite particles/poly(ester-urethane) scaffolds were implanted into the flank of FVB/N-TgN (Tie2/GFP) 287 Sato mice to allow the ingrowth of a granulation tissue with green fluorescent protein (GFP)-positive blood vessels.

Differential response of human bone marrow stromal cells to either TGF-β(1) or rhGDF-5.

Cell therapy along with growth factor injection is currently widely investigated to restore the intervertebral disc. However, there is increasing evidence that transplanted unconditioned bone marrow-derived stromal cells (BMSCs) cannot thrive in the intervertebral disc "niche". Moreover, uncertainty exists with respect to the cell phenotype that would be suitable to inject.

Short-term cultivation of in situ prevascularized tissue constructs accelerates inosculation of their preformed microvascular networks after implantation into the host tissue.

Inosculation of preformed microvessels with the host microvasculature represents a promising approach to accelerate vascularization of tissue constructs. Herein, we analyzed whether cultivation of prevascularized tissue constructs promotes inosculation by reducing the perivascular cell coverage of the preformed microvessels. Poly(ester-urethane) scaffolds were implanted into FVB/N-TgN (Tie2/green fluorescent protein [GFP]) 287 Sato mice to generate prevascularized tissue constructs with GFP-positive microvessels.

The osteogenic differentiation of human osteoprogenitor cells on Anodic-Plasma-Chemical treated Ti6Al7Nb.

Biological integration of an implant to surrounding bone is an important event for its clinical success and is driven by numerous factors, including the attraction of bone forming cells. The implant's surface properties influence the initial cell response at the cell/material interface, ultimately affecting the rate and quality of new tissue formation and the stability of the implant. As a consequence, various surface treatments have been developed to increase the clinical performance of titanium-based implants.

Varying regional topology within knee articular chondrocytes under simulated in vivo conditions.

Topographical cartilage variation across the knee joint has been previously reported, but there is only limited information on such gene expression profiles. Articular chondrocytes from eight different topographical regions of bovine knee joints were seeded within three-dimensional scaffolds and further cultured under static conditions (unloaded control group) or subjected to an artificial joint environment within a bioreactor (loaded group). Constructs were analyzed for glycosaminoglycan (GAG), DNA, and expression of Collagen-1,-2,-10, Aggrecan, COMP, Sox9, PRG-4, PTHrp, and MMP-1,-3,-13 mRNA after 2 weeks of in vitro culture.

Region-dependent aggrecan degradation patterns in the rat intervertebral disc are affected by mechanical loading in vivo.

Study Design: Immunoblotting study to evaluate aggrecan degradation patterns in rat intervertebral discs (IVDs) subjected to mechanical overload.

Objective: To evaluate the effects of in vivo dynamic compression overloading on aggrecan degradation products associated with matrix metalloproteinase (MMP) and aggrecanase activity in different regions of the IVD.

Summary Of Background Data: Aggrecan cleavage at the MMP and aggrecanase sites is an important event in human IVD aging, with distinct cleavage patterns in the anulus and nucleus regions.

Mechanical properties and cytocompatibility of poly(ε-caprolactone)-infiltrated biphasic calcium phosphate scaffolds with bimodal pore distribution.

Biphasic calcium phosphate scaffolds have attracted interest because they have good osteoconductivity and a resorption rate close to that of new bone ingrowth, but their brittleness limits their potential applications. In this study, we show how the infiltration of biphasic calcium phosphate scaffolds with poly(ε-caprolactone) improves their mechanical properties. It was found that the polymer effectively contributes to energy to failure enhancement in bending, compressive and tensile tests.

The combined effects of limited nutrition and high-frequency loading on intervertebral discs with endplates.

Study Design: Whole ovine caudal intervertebral discs were cultured under simulated-physiologic or high-frequency loading and either sufficient or limited nutrition for 7 days.

Objective: To study the effect of high-frequency loading under sufficient or limited glucose conditions and to investigate the additive effects of load and nutrition on cell survival, gene expression, and cell activity after 7 days of culture.

Summary Of Background Data: Limited nutrition and certain mechanical stimuli are generally believed to be etiologic factors for disc degeneration.

Tailoring thermoreversible hyaluronan hydrogels by "click" chemistry and RAFT polymerization for cell and drug therapy.

Thermoreversible hydrogels are promising matrices for tissue-engineered cartilage and spine constructs. They require specific properties during all the stages of a cell therapy (e.g.

Thiol-containing degradable poly(thiourethane-urethane)s for tissue engineering.

Poly(thiourethane-urethane)s with varying amounts of sulphur were synthesised by a two-step polycondensation consisting of the sequential addition of 1,6-hexamethylene diisocyanate and bis(2-mercaptoethyl) ether in a poly(epsilon-caprolactone) diol solution. Polymers prepared had high weight-average molecular weight and typical microdomains separation, as shown by size-exclusion chromatography and thermal analysis. Polymer surfaces were characterized by X-ray photoelectron spectroscopy and atomic force microscopy.