Microencapsulated stem cells reduce cartilage damage in a material dependent manner following minimally invasive intra-articular injection in an OA rat model.

Osteoarthritis (OA) is a degenerative disease of the joints for which no curative treatment exists. Intra-articular injection of stem cells is explored as a regenerative approach, but rapid clearance of cells from the injection site limits the therapeutic outcome. Microencapsulation of mesenchymal stem cells (MSCs) can extend the retention time of MSCs, but the outcomes of the few studies currently performed are conflicting.

Injectable Cell-Laden Polysaccharide Hydrogels: In Vivo Evaluation of Cartilage Regeneration.

Previously, 5% / hyaluronic acid-tyramine (HA-TA) and dextran-tyramine (Dex-TA) enzymatically cross-linked hybrid hydrogels were demonstrated to provide a mechanically stable environment, maintain cell viability, and promote cartilaginous-specific matrix deposition in vitro. In this study, 5% / hybrid hydrogels were combined with human mesenchymal stem cells (hMSCs), bovine chondrocytes (bCHs), or a combination of both in a 4:1 ratio and subcutaneously implanted in the backs of male and female nude rats to assess the performance of cell-laden hydrogels in tissue formation. Subcutaneous implantation of these biomaterials showed signs of integration of the gels within the host tissue.

Engineering of Optimized Hydrogel Formulations for Cartilage Repair.

The ideal scaffold for cartilage regeneration is expected to provide adequate mechanical strength, controlled degradability, adhesion, and integration with the surrounding native tissue. As it does this, it mimics natural ECMs functions, which allow for nutrient diffusion and promote cell survival and differentiation. Injectable hydrogels based on tyramine (TA)-functionalized hyaluronic acid (HA) and dextran (Dex) are a promising approach for cartilage regeneration.

An important step towards a prevascularized islet microencapsulation device: in vivo prevascularization by combination of mesenchymal stem cells on micropatterned membranes.

Extrahepatic transplantation of islets of Langerhans could aid in better survival of islets after transplantation. When islets are transfused into the liver 60-70% of them are lost immediately after transplantation. An important factor for a successful extrahepatic transplantation is a well-vascularized tissue surrounding the implant.

Trophic Effects of Mesenchymal Stem Cells in Tissue Regeneration.

Mesenchymal stem cells (MSCs) are considered to hold great therapeutic value for cell-based therapy and for tissue regeneration in particular. Recent evidence indicates that the main underlying mechanism for MSCs' beneficial effects in tissue regeneration is based on their capability to produce a large variety of bioactive trophic factors that stimulate neighboring parenchymal cells to start repairing damaged tissues. These new findings could potentially replace the classical paradigm of MSC differentiation and cell replacement.

Kinetically stable metal ligand charge transfer complexes as crosslinks in nanogels/hydrogels: Physical properties and cytotoxicity.

Unlabelled: A terpyridine end-functionalized 8-arm poly(ethylene glycol) was prepared using the reaction of a 4'-aminopentanoxy substituted terpyridine with a p-nitrophenyl chloroformate activated PEG-(OH)8. Supramolecular complexation of the polymer terpyridine moieties by Fe(2+) ions was investigated using NMR, UV-Vis and dynamic light scattering experiments. At low concentrations addition of Fe(2+) ions to an aqueous solution of the polymer conjugate afforded nanogels with a single size distribution around 250 nm.

Effects of in vitro chondrogenic priming time of bone-marrow-derived mesenchymal stromal cells on in vivo endochondral bone formation.

Recapitulation of endochondral ossification leads to a new concept of bone tissue engineering via a cartilage intermediate as an osteoinductive template. In this study, we aimed to investigate the influence of in vitro chondrogenic priming time for the creation of cartilage template on the in vivo endochondral bone formation both qualitatively and quantitatively. To this end, rat bone-marrow-derived mesenchymal stromal cells (MSCs) were seeded onto two scaffolds with distinguished features: a fibrous poly(lactic-co-glycolic acid)/poly(ε-caprolactone) electrospun scaffold (PLGA/PCL) and a porous hydroxyapatite/tricalcium phosphate composite (HA/TCP).

Biological evaluation of porous aliphatic polyurethane/hydroxyapatite composite scaffolds for bone tissue engineering.

Biomaterial scaffolds meant to function as supporting structures to osteogenic cells play a pivotal role in bone tissue engineering. Recently, we synthesized an aliphatic polyurethane (PU) scaffold via a foaming method using non-toxic components. Through this procedure a uniform interconnected porous structure was created.

Human periodontal ligament derived progenitor cells: effect of STRO-1 cell sorting and Wnt3a treatment on cell behavior.

Objectives: STRO-1 positive periodontal ligament cells (PDLCs) and unsorted PDLCs have demonstrated potential for periodontal regeneration, but the comparison between unsorted cells and the expanded STRO-1 sorted cells has never been reported. Additionally, Wnt3a is involved in cell proliferation thus may benefit in vitro PDLC expansion. The aim was to evaluate the effect of STRO-1 cell sorting and Wnt3a treatment on cell behavior of human PDLCs (hPDLCs).

Bone forming capacity of cell- and growth factor-based constructs at different ectopic implantation sites.

The aim of this study was to compare the effect of implantation site (i.e., subcutaneous, SQ vs.

Synergistic effects of bisphosphonate and calcium phosphate nanoparticles on peri-implant bone responses in osteoporotic rats.

The prevalence of osteoporosis will increase within the next decades due to the aging world population, which can affect the bone healing response to dental and orthopedic implants. Consequently, local drug targeting of peri-implant bone has been proposed as a strategy for the enhancement of bone-implant integration in osteoporotic conditions. In the present study, an established in-vivo femoral condyle implantation model in osteoporotic and healthy bone is used to analyze the osteogenic capacity of titanium implants coated with bisphosphonate (BP)-loaded calcium phosphate nanoparticles (nCaP) under compromised medical conditions.

Enzymatic control of chitosan gelation for delivery of periodontal ligament cells.

The aim of this study is to optimize enzymatic control over gelation of chitosan-based hydrogels for the delivery of periodontal ligament cells (PDLCs). The results reveal that the gelation time, strength, and degradation rate of the chitosan hydrogels can be controlled precisely by variation of the urea and urease concentrations. PDLCs remain viable inside these hydrogels for up to 30 days.

In vitro and in vivo angiogenic capacity of BM-MSCs/HUVECs and AT-MSCs/HUVECs cocultures.

The aim of this study was to comparatively evaluate the angiogenic capacity of cocultures using either human bone marrow- or human adipose tissue-derived mesenchymal stem cells (MSCs) (BM- or AT-MSCs) with human umbilical vein endothelial cells (HUVECs) both in vitro and in vivo at early time points (i.e. days 3 and 7).

Concise review: cell-based strategies in bone tissue engineering and regenerative medicine.

Cellular strategies play an important role in bone tissue engineering and regenerative medicine (BTE/RM). Variability in cell culture procedures (e.g.

Size matters: effects of PLGA-microsphere size in injectable CPC/PLGA on bone formation.

The aim of this study was to evaluate the effect of PLGA microsphere dimensions on bone formation after injection of calcium phosphate cement (CPC)/PLGA in a guinea pig tibial intramedullarly model. To this end, injectable CPC/PLGA formulations were prepared using PLGA microspheres with either a small (~25 µm) or large (~100 µm) diameter, which were incorporated at a 20:80 ratio (wt%) within apatite CPC. Both CPC/PLGA formulations were injected into a marrow-ablated tibial intramedullary cavity and, after an implantation period of 12 weeks, histology and histomorphometry were used to address bone formation.

Biomaterial strategies for stem cell maintenance during in vitro expansion.

Stem cells, having the potential for self-renewal and multilineage differentiation, are the building blocks for tissue/organ regeneration. Stem cells can be isolated from various sources but are, in general, available in too small numbers to be used directly for clinical purpose without intermediate expansion procedures in vitro. Although this in vitro expansion of undifferentiated stem cells is necessary, stem cells typically diminish their ability to self-renew and proliferate during passaging.

Effects of continuous passaging on mineralization of MC3T3-E1 cells with improved osteogenic culture protocol.

The murine-derived MC3T3-E1 cell line provided by the American Type Culture Collection (ATCC) is a well-known osteogenic cell culture model system to test materials in vitro. However, the effect of passaging on its mineralization capacity has never been described and their culture supplements can be further optimized. Therefore, we evaluated the influence of the passage number and different osteogenic culture supplements, including ascorbic acid (AsAP) and dexamethasone (Dex) on the osteogenic capacity of MC3T3-E1 cells.

In vivo bone regeneration using tubular perfusion system bioreactor cultured nanofibrous scaffolds.

The use of bioreactors for the in vitro culture of constructs for bone tissue engineering has become prevalent as these systems may improve the growth and differentiation of a cultured cell population. Here we utilize a tubular perfusion system (TPS) bioreactor for the in vitro culture of human mesenchymal stem cells (hMSCs) and implant the cultured constructs into rat femoral condyle defects. Using nanofibrous electrospun poly(lactic-co-glycolic acid)/poly(ε-caprolactone) scaffolds, hMSCs were cultured for 10 days in vitro in the TPS bioreactor with cellular and acellular scaffolds cultured statically for 10 days as a control.

Comparison of cell-loading methods in hydrogel systems.

Bone regenerative medicine, based on the combined use of cells and scaffolds, represents a promising strategy in bone regeneration. Hydrogels have attracted huge interests for application as a scaffold for minimally invasive surgery. Collagen and oligo(poly(ethylene glycol)fumarate) (OPF) hydrogels are the representatives of two main categories of hydrogels, that is, natural- and synthetic-based hydrogels.

Adipose tissue-derived mesenchymal stem cells as monocultures or cocultures with human umbilical vein endothelial cells: performance in vitro and in rat cranial defects.

The aim of this study was to compare the osteogenic capacity between human adipose tissue-derived mesenchymal stem cells (AT-MSCs) and their cocultures with human umbilical vein endothelial cells (HUVECs) in vitro and their biological performance in vivo. First, the optimal cell ratio in cocultures for osteogenic differentiation was determined by seeding AT-MSCs and HUVECs in ratios varying from 100:0 to 0:100 on tissue culture plates. Afterward, AT-MSCs and AT-MSCs/HUVECs (50:50) were seeded on porous titanium fiber mesh scaffolds (Ti) for both in vitro and in vivo osteogenic evaluation.

Osteogenic capacity of human BM-MSCs, AT-MSCs and their co-cultures using HUVECs in FBS and PL supplemented media.

Human bone marrow-derived mesenchymal stem cells (BM-MSCs) and human adipose tissue-derived mesenchymal stem cells (AT-MSCs) are the most frequently used stem cells in tissue engineering. Due to major clinical demands, it is necessary to find an optimally safe and efficient way for large-scale expansion of these cells. Considering the nutritional source in the culture medium and method, this study aimed to analyze the effects of FBS- and PL-supplemented media on osteogenesis in stem cell mono- and co-cultures with human umbilical vein endothelial cells (HUVECs).

In vivo bone generation via the endochondral pathway on three-dimensional electrospun fibers.

A new concept of generating bone tissue via the endochondral route might be superior to the standard intramembranous ossification approach. To implement the endochondral approach, suitable scaffolds are required to provide a three-dimensional (3-D) substrate for cell population and differentiation, and eventually for the generation of osteochondral tissue. Therefore, a novel wet-electrospinning system, using ethanol as the collecting medium, was exploited in this study to fabricate a cotton-like poly(lactic-co-glycolic acid)/poly(ε-caprolactone) scaffold that consisted of a very loose and uncompressed accumulation of fibers.

In-vivo generation of bone via endochondral ossification by in-vitro chondrogenic priming of adult human and rat mesenchymal stem cells.

Background: Bone grafts are required to repair large bone defects after tumour resection or large trauma. The availability of patients' own bone tissue that can be used for these procedures is limited. Thus far bone tissue engineering has not lead to an implant which could be used as alternative in bone replacement surgery.

Coculture of osteoblasts and endothelial cells: optimization of culture medium and cell ratio.

Vascularization strategies in cell-based bone tissue engineering depend on optimal culture conditions. The present study aimed to determine optimal cell culture medium and cell ratio for cocultures of human marrow stromal cells (HMSCs) and human umbilical vein endothelial cells (HUVECs) in view of both osteogenic and angiogenic outcome parameters upon two-dimensional and three-dimensional culture conditions. Cultures were performed in four different media: osteoblastic cell proliferation medium, osteogenic medium (OM), endothelial medium, and a 1:1 mixture of the latter two media.

Differential bone-forming capacity of osteogenic cells from either embryonic stem cells or bone marrow-derived mesenchymal stem cells.

For more than a decade, human mesenchymal stem cells (hMSCs) have been used in bone tissue-engineering research. More recently some of the focus in this field has shifted towards the use of embryonic stem cells. While it is well known that hMSCs are able to form bone when implanted subcutaneously in immune-deficient mice, the osteogenic potential of embryonic stem cells has been mainly assessed in vitro.