Advances in skeletal tissue engineering with hydrogels

Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218, USA.
Orthodontics and Craniofacial Research (Impact Factor: 1.06). 09/2005; 8(3):150-61. DOI: 10.1111/j.1601-6343.2005.00335.x
Source: PubMed


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.
Multilayered hydrogel systems were developed to coculture different cell types and develop osteochondral tissues for applications including the temporomandibular joint.
Hydrogels are one form of scaffold that can be applied to cartilage and bone repair using fully differentiated cells, adult and embryonic stem cells.
Case studies represent an overview of our laboratory's investigations.
Bilayered scaffolds to promote tissue development and the formation of more complex osteochondral tissues were developed and proved to be effective.
Tissue engineering provides a venue to investigate tissue development of mutant or diseased cells and potential therapeutics.

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    • "The interplay between these factors and the precise sequences of factors leading to the commitment and formation of tissues is not fully understood. PEG-based hydrogels have been utilized as cartilage tissue engineering scaffolds (Elisseeff et al. 2005). In addition, MSCs encapsulated in PEGDA hydrogels show chondrogenic differentiation upon exposure to TGF-β3 (Williams et al. 2003). "
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    ABSTRACT: Bone-marrow-derived mesenchymal stem cells (MSCs) are candidates for regeneration applications in musculoskeletal tissue such as cartilage and bone. Various soluble factors in the form of growth factors and cytokines have been widely studied for directing the chondrogenic and osteogenic differentiation of MSCs, but little is known about the way that the composition of extracellular matrix (ECM) components in three-dimensional microenvironments plays a role in regulating the differentiation of MSCs. To define whether ECM components influence the regulation of osteogenic and chondrogenic differentiation by MSCs, we encapsulated MSCs in poly-(ethylene glycol)-based (PEG-based) hydrogels containing exogenous type I collagen, type II collagen, or hyaluronic acids (HA) and cultured them for up to 6 weeks in chondrogenic medium containing transforming growth factor-β1 (10 ng/ml) or osteogenic medium. Actin cytoskeleton organization and cellular morphology were strongly dependent on which ECM components were added to the PEG-based hydrogels. Additionally, chondrogenic differentiation of MSCs was marginally enhanced in collagen-matrix-based hydrogels, whereas osteogenic differentiation, as measured by calcium accumulation, was induced in HA-containing hydrogels. Thus, the microenvironments created by exogenous ECM components seem to modulate the fate of MSC differentiation.
    Cell and Tissue Research 06/2011; 344(3):499-509. DOI:10.1007/s00441-011-1153-2 · 3.57 Impact Factor
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    • "Tissue engineering has demonstrated significant potential for cartilage defect repair and could ultimately reduce the need for tissue transplants and prosthetic implants. Hydrogels are a class of scaffold that are commonly used in cartilage tissue engineering and include alginate, agarose, poly(ethylene glycol) (PEG), poly(vinyl alcohol) (PVA), pluronics, chitosan, collagen and fibrin as examples (Lum and Elisseeff 2003; Elisseeff et al. 2005). A significant benefit of hydrogels is their potential use as an in situ forming scaffold for cartilage defect repair. "
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    ABSTRACT: Agarose hydrogels are commonly used for cartilage tissue engineering studies and to provide a three dimensional environment to investigate cellular mechanobiology. Interpreting the results of such studies requires accurate quantification of the mechanical properties of the hydrogel. There is significant variation in the reported mechanical properties of agarose hydrogels, and little is reported on the influence of factors associated with mixing these hydrogels with cell suspensions on their initial mechanical properties. The objective of this study was to determine the influence of agarose concentration, the cooling rate during gelation, the thermal history following gelation and the cell seeding density on the initial mechanical properties of agarose hydrogels. The average ramp modulus of 2% agarose gel in tension was 24.9 kPa (+/-1.7, n=10), compared with 55.6 kPa (+/-0.5, n=10) in compression. The average tensile equilibrium modulus was 39.7 kPa (+/-5.7, n=6), significantly higher than the compressive equilibrium modulus of 14.2 kPa (+/-1.6, n=10). The equilibrium and dynamic compressive modulus of agarose hydrogels were observed to reduce if maintained at 37 ( composite function)C following gelation compared with samples maintained at room temperature. Depending on the methodology used to encapsulate chondrocytes within agarose hydrogels, the equilibrium compressive modulus was found to be significantly higher for acellular 2% agarose gels compared with 2% agarose gels seeded at approximately 40 x 10(6) cells/mL. These results have important implications for interpreting the results of chondrocyte mechanobiology studies in agarose hydrogels.
    11/2009; 2(5):512-21. DOI:10.1016/j.jmbbm.2008.12.007
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    • "Hydrogels are promising polymeric biomaterials for tissue engineering purposes due to their ability to absorb water and possess tissue-like elasticity. Cells can thus be suspended in the polymer solution and can be polymerized in situ within a defect site in the body providing strategies for tissue engineering (Peppas et al.,1987; Anseth et al., 1996; Elisseeff et al., 2005). However, the cells encapsulated in the hydrogels seem to be trapped and have restricted secretion of adhesion proteins and as a result there is limited interactions between the cell surface integrins and the surrounding gel environment (Nuttelman et al., 2005). "
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    ABSTRACT: The periodontal ligament (PDL) is a specialized connective tissue that connects the surface of the tooth root with the bony tooth socket. The healthy PDL harbors stem cell niches and extracellular matrix (ECM) microenvironments that facilitate periodontal regeneration. During periodontal disease, the PDL is often compromised or destroyed, reducing the life-span of the tooth. In order to explore new approaches toward the regeneration of diseased periodontal tissues, we have tested the effect of periodontal ECM signals, fibroblast growth factor 2 (FGF2), connective tissue growth factor (CTGF), and the cell adhesion peptide Arg-Gly-Asp (RGD) on the differentiation of two types of periodontal progenitor cells, PDL progenitor cells (PDLPs) and dental follicle progenitor cells (DFCs). Our studies documented that CTGF and FGF2 significantly enhanced the expression of collagens I & III, biglycan and periostin in tissue engineered regenerates after 4 weeks compared to untreated controls. Specifically, CTGF promoted mature PDL-like tissue regeneration as demonstrated by dense periostin localization in collagen fiber bundles. CTGF and FGF2 displayed synergistic effects on collagen III and biglycan gene expression, while effects on mineralization were antagonistic to each other: CTGF promoted while FGF2 inhibited mineralization in PDL cell cultures. Incorporation of RGD peptides in hydrogel matrices significantly enhanced attachment, spreading, survival and mineralization of the encapsulated DFCs, suggesting that RGD additives might promote the use of hydrogels for periodontal mineralized tissue engineering. Together, our studies have documented the effect of three key components of the periodontal ECM on the differentiation of periodontal progenitor populations.
    Differentiation 05/2009; 78(2-3):79-90. DOI:10.1016/j.diff.2009.03.005 · 3.44 Impact Factor
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