Hydrogel-β-TCP scaffolds and stem cells for tissue engineering bone (original) (raw)

Comparison of hydrogels in the in vivo formation of tissue-engineered bone using mesenchymal stem cells and beta-tricalcium phosphate

Tissue engineering, 2007

Availability of grafts and morbidity at the donor site limit autologous transplantation in patients requiring bone reconstruction. A tissue-engineering approach can overcome these limitations by producing bone-like tissue of custom shape and size from isolated cells. Several hydrogels facilitate osteogenesis on porous scaffolds; however, the relative suitability of various hydrogels has not been rigorously assessed. Fibrin glue, alginate, and collagen I hydrogels were mixed with swine bone marrow-derived differentiated mesenchymal stem cells (MSCs), applied to 3-dimensionally printed porous beta-tricalcium phosphate (beta-TCP) scaffolds and implanted subcutaneously in nude mice. Although noninvasive assessment of osteogenesis in 3 dimensions is desirable for monitoring new bone formation in vivo, correlations with traditional histological and mechanical testing need to be established. High-resolution volumetric computed tomography (VCT) scanning, histological examination, biomechani...

Advances in skeletal tissue engineering with hydrogels

Orthodontics and Craniofacial Research, 2005

Objectives -Tissue engineering has the potential to make a significant impact on improving tissue repair in the craniofacial system. The general strategy for tissue engineering includes seeding cells on a biomaterial scaffold. The number of scaffold and cell choices for tissue engineering systems is continually increasing and will be reviewed.

Tissue engineering of bone: search for a better scaffold

Orthodontics and Craniofacial Research, 2005

Structured Abstract Authors -Mastrogiacomo M, Muraglia A, Komlev V, Peyrin F, Rustichelli F, Crovace A, Cancedda R Background -Large bone defects still represent a major problem in orthopedics. Traditional bone-repair treatments can be divided into two groups: the bone transport (Ilizarov technology) and the graft transplant (autologous or allogeneic bone grafts). Thus far, none of these strategies have proven to be always resolving. As an alternative, a tissue engineering approach has been proposed where osteogenic cells, bioceramic scaffolds, growth factors and physical forces concur to the bone defect repair. Different sources of osteoprogenitor cells have been suggested, bone marrow stromal cells (BMSC) being in most cases the first choice. Methods and Results -In association with mineral tridimensional scaffolds, BMSC form a primary bone tissue which is highly vascularized and colonized by host hemopoietic marrow. The chemical composition of the scaffold is crucial for the osteoconductive properties and the resorbability of the material. In addition, scaffolds should have an internal structure permissive for vascular invasion. Porous bioceramics [hydroxyapatite (HA) and tricalcium phosphate] are osteoconductive and are particularly advantageous for bone tissue engineering application as they induce neither an immune nor an inflammatory response in the implanted host.

A collagen-based hydrogel containing tacrolimus for bone tissue engineering

Drug Delivery and Translational Research

Bone tissue engineering aims to develop bone graft structure that can heal bone defects without using autografts or allografts. The current study was conducted to promote bone regeneration using a collagen type I hydrogel containing tacrolimus. For this purpose, different amounts of tacrolimus (10 μg/ml, 100 μg/ml, and 1000 μg/ml) were loaded into the hydrogel. The resulting drug-loaded hydrogels were characterized for their porosity, swelling capacity, weight loss, drug release, blood compatibility, and cell proliferation (MTT). For functional analysis, the developed hydrogel surrounded by a film made of gelatin and polycaprolactone (PCL) was administrated in the calvarias defect of Wistar rats. The results indicated that the hydrogel has a porosity of 89.2 ± 12.5% and an appropriate swelling, drug release, and blood compatibility behavior. The in vitro results indicated that the collagen hydrogel containing 1000 μg tacrolimus was adequate in terms of cell proliferation. Finally, in vivo studies provided some evidence of the potential of the developed hydrogel for bone healing.

Effect of Cell Origin and Timing of Delivery for Stem Cell-Based Bone Tissue Engineering Using Biologically Functionalized Hydrogels

Tissue Engineering Part A, 2015

Despite progress in bone tissue engineering, the healing of critically sized diaphyseal defects remains a clinical challenge. A stem cell-based approach is an attractive alternative to current treatment techniques. The objective of this study was to examine the ability of adult stem cells to enhance bone formation when co-delivered with the osteoinductive factor bone morphogenetic protein-2 (BMP-2) in a biologically functionalized hydrogel. First, adipose and bone marrow-derived mesenchymal stem cells (ADSCs and BMMSCs) were screened for their potential to form bone when delivered in an RGD functionalized alginate hydrogel using a subcutaneous implant model. BMMSCs co-delivered with BMP-2 produced significantly more mineralized tissue compared with either ADSCs co-delivered with BMP-2 or acellular hydrogels containing BMP-2. Next, the ability of BMMSCs to heal a critically sized diaphyseal defect with a nonhealing dose of BMP-2 was tested using the alginate hydrogel as an injectable cell carrier. The effect of timing of therapeutic delivery on bone regeneration was also tested in the diaphyseal model. A 7 day delayed injection of the hydrogel into the defect site resulted in less mineralized tissue formation than immediate delivery of the hydrogel. By 12 weeks, BMMSC-loaded hydrogels produced significantly more bone than acellular constructs regardless of immediate or delayed treatment. For immediate delivery, bridging of defects treated with BMMSC-loaded hydrogels occurred at a rate of 75% compared with a 33% bridging rate for acellular-treated defects. No bridging was observed in any of the delayed delivery samples for any of the groups. Therefore, for this cell-based bone tissue engineering approach, immediate delivery of constructs leads to an overall enhanced healing response compared with delayed delivery techniques. Further, these studies demonstrate that co-delivery of adult stem cells, specifically BMMSCs, with BMP-2 enhances bone regeneration in a critically sized femoral segmental defect compared with acellular hydrogels containing BMP-2.

In vivo Bone Formation by Canine Mesenchymal Stem Cells Loaded onto HA/TCP Scaffolds: Qualitative and Quantitative Analysis

Objective: Biphasic ceramics of hydroxyapatite and three calcium phosphate (HA/ TCP) are increasingly being used as a bone substitute in regenerative surgery. To increase the bone forming capacities, HA/TCP Scaffolds could be enriched with osteogenic factor like mesenchymal stem cells (MSCs) which is the subject of present study. Materials and Methods: Passaged-3 culture-expanded MSCs of canines bone marrow were suspended in a diluted collagen gel and loaded onto commercially-available HA/TCP ceramics. The cell-loaded scaffolds were then autologously implanted along with the control cell-free scaffolds in masseter muscles of the four mongrel dogs. Eight weeks later, the parts of their muscles including the implants were prepared for a light microscopy. To quantify the amount of bone formation, the slides of both studied groups were photographed and the percent area of the newly formed bone was calculated using Image-Pro Plust software. Results: According to our observations, the implants were appeared to be encapsulated by fibrous tissue within the muscle. No cartilage tissues were observed in implantation site. Histological observation indicated that ectopic bone was formed in both MSCs-loaded scaffolds as well as the control cell-free implants. The percentage of newly formed bone for cell loaded HA/TCP scaffolds was %29.12±6.01 compared to %23.55±4.99 of the cell-free implants (p<0.05). Furthermore, lamellar mature bone was only observed in cells/scaffold groups. Conclusion: Taken together, it seems that MSCs enhance bone formation capacity of HA/TCP. The formed bone following MSCs/scaffold composite implantation appeared to be histologically lymature lamellar bone.