A highly organized three-dimensional alginate scaffold for cartilage tissue engineering prepared by microfluidic technology

Wang, Chen Chie; Yang, Kai Chiang; Lin, Keng Hui; Liu, Hwa Chang; Lin, Feng Huei

doi:10.1016/j.biomaterials.2011.06.018

Cited by 176 publications

(142 citation statements)

References 51 publications

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“…70 Hydrogels based on biopolymers mimic many features of the 71 ECM and thus have the potential to direct the migration, growth 72 and organization of cells during tissue regeneration [10]. A wide 73 range of natural and synthetic polymeric materials have been 74 investigated as scaffolding for cartilage repair, including alginate 75 [11,12], agarose [13,14], gelatin [15], hyaluronic acid [16,17], gel-76 lan gum [18,19], carrageenan [20,21], and fibrin [22,23], aiming 77 at supporting the in vitro and in vivo chondrogenic differentiation 78 of Mesenchymal Stem Cells (MSCs) [2,3]. http [2,24].…”

Section: Introductionmentioning

confidence: 99%

Natural assembly of platelet lysate-loaded nanocarriers into enriched 3D hydrogels for cartilage regeneration

et al. 2015

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The role of Platelet Lysates (PLs) as a source of growth factors (GFs) and as main element of three-dimensional (3D) hydrogels has been previously described. However, the resulting hydrogels usually suffer from high degree of contraction, limiting their usefulness. This work describes the development of a stable biomimetic 3D hydrogel structure based on PLs, through the spontaneous assembling of a high concentration of chitosan-chondroitin sulfate nanoparticles (CH/CS NPs) with PLs loaded by adsorption. The interactions between the NPs and the lysates resemble the ones observed in the extracellular matrix (ECM) native environment between glycosaminoglycans and ECM proteins. In vitro release studies were carried out focusing on the quantification of PDGF-BB and TGF-β1 GFs. Human adipose derived stem cells (hASCs) were entrapped in these 3D hydrogels and cultured in vitro under chondrogenic stimulus, in order to assess their potential use for cartilage regeneration. Histological, immunohistological and gene expression analysis demonstrated that the PL-assembled constructs entrapping hASCs exhibited results similar to the positive control (hASCS cultured in pellets), concerning the levels of collagen II expression and immunolocalization of collagen type I and II and aggrecan. Moreover, the deposition of new cartilage ECM was detected by alcian blue and safranin-O positive stainings. This work demonstrates the potential of PLs to act simultaneously as a source/carrier of GFs and as a 3D structure of support, through the application of a "bottom-up" approach involving the assembly of NPs, resulting in an enriched construct for cartilage regeneration applications.

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Section: Introductionmentioning

confidence: 99%

Natural assembly of platelet lysate-loaded nanocarriers into enriched 3D hydrogels for cartilage regeneration

et al. 2015

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“…Microfluidic technology holds promise for such an approach, enabling the formation of microspheres with < 500 mm diameter and a very narrow particle size distribution. 33,34 In addition to decreasing the size of the microbeads, it is also desirable to find biomaterials with improved bioactivity to make an optimal scaffold for the encapsulation of MSCs. It is well known that bone extracellular matrix (ECM) components play a crucial role in controlling osteoblast gene expression through interaction with cell-surface receptors of the integrin family.…”

Section: Introductionmentioning

confidence: 99%

Bone Regeneration Potential of Stem Cells Derived from Periodontal Ligament or Gingival Tissue Sources Encapsulated in RGD-Modified Alginate Scaffold

Moshaverinia

Chen

et al. 2013

Tissue Engineering Part A

117

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Mesenchymal stem cells (MSCs) provide an advantageous alternative therapeutic option for bone regeneration in comparison to current treatment modalities. However, delivering MSCs to the defect site while maintaining a high MSC survival rate is still a critical challenge in MSC-mediated bone regeneration. Here, we tested the bone regeneration capacity of periodontal ligament stem cells (PDLSCs) and gingival mesenchymal stem cells (GMSCs) encapsulated in a novel RGD-(arginine-glycine-aspartic acid tripeptide) coupled alginate microencapsulation system in vitro and in vivo. Five-millimeter-diameter critical-size calvarial defects were created in immunocompromised mice and PDLSCs and GMSCs encapsulated in RGD-modified alginate microspheres were transplanted into the defect sites. New bone formation was assessed using microcomputed tomography and histological analyses 8 weeks after transplantation. Results confirmed that our microencapsulation system significantly enhanced MSC viability and osteogenic differentiation in vitro compared with non-RGD-containing alginate hydrogel microspheres with larger diameters. Results confirmed that PDLSCs were able to repair the calvarial defects by promoting the formation of mineralized tissue, while GMSCs showed significantly lower osteogenic differentiation capability. Further, results revealed that RGD-coupled alginate scaffold facilitated the differentiation of oral MSCs toward an osteoblast lineage in vitro and in vivo, as assessed by expression of osteogenic markers Runx2, ALP, and osteocalcin. In conclusion, these results for the first time demonstrated that MSCs derived from orofacial tissue encapsulated in RGD-modified alginate scaffold show promise for craniofacial bone regeneration. This treatment modality has many potential dental and orthopedic applications.

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“…Using alginate as matrix for embedding human chondrocytes to form a three-dimensional construct, the physiological environment of cartilage tissue is imitated well [7,8]. Images of live/dead staining displayed round-shaped phenotype of chondrocytes encapsulated within alginate matrix as single cells or a cell couple indicating cartilage-like arrangement as clusters.…”

Section: Discussionmentioning

confidence: 99%

Transient supplementation of growth factor TGF-β1 effectively initiates chondrogenic redifferentiation of human chondrocytes

Hiemer

Achenbach

Pasold

et al. 2017

Current Directions in Biomedical Engineering

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Cartilage tissue is avascular with less regeneration potential and therefore, cartilage regeneration is still a major challenge for therapeutic approaches. Commonly used treatment strategies involve the transplantation of autologous chondrocytes into the defect. Before that, it is required to increase the cell number in vitro resulting in unwanted chondrocyte dedifferentiation. This could impair subsequent tissue regeneration. Both growth factors TGF-ß1 and IGF-1 are used as strong inducer of chondrogenic redifferentiation, however, a controlled application of TGF-ß1 is essential to avoid adverse effects. Therefore, in the present study, we investigated the time-dependent influence of TGF-ß1 administration on chondrocyte redifferentiation.Human chondrocytes were embedded in alginate and cultured in serum-free DMEM containing ascorbic acid, dexamethasone, ITS TM and IGF-1. TGF-β1 was supplemented for 3, 7 and 21 days. Afterwards, cell viability and synthesis of extracellular matrix (ECM) proteins was analyzed by histological staining.Live/dead staining of chondrocytes incubated with TGF-β1 for 21 days displayed an enhanced proliferation and formation of cell clusters resulting in excessive outgrowth of fibroblastic-like cells. However, exposure to TGF-β1 over only 7 days caused also cell clustering with moderate cell proliferation. Additionally, after 21 days of cultivation proteoglycan synthesis was identified by alcian blue staining after both TGF-β1 supplementation for 21 and also 7 days. Aggrecan was also detected in the periphery of the cell clusters after TGF-β1 incubation for only 7 days. Chondrocytes lacked proteoglycan expression after three-day TGF-β1 administration.We could show, that prolonged administration of TGF-β1 results in massive proliferation of chondrocytes which is accompanied by cell outgrowth. We found that TGF-ß1 exposure for seven days is sufficient for achievement of cell clustering without excessive cell proliferation, which is important for inducing subsequent chondrogenic differentiation. Results indicate that even an initial TGF-β1 administration could be sufficient for inducing chondrocyte proliferation and differentiation in vitro.

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A highly organized three-dimensional alginate scaffold for cartilage tissue engineering prepared by microfluidic technology

Cited by 176 publications

References 51 publications

Natural assembly of platelet lysate-loaded nanocarriers into enriched 3D hydrogels for cartilage regeneration

Natural assembly of platelet lysate-loaded nanocarriers into enriched 3D hydrogels for cartilage regeneration

Bone Regeneration Potential of Stem Cells Derived from Periodontal Ligament or Gingival Tissue Sources Encapsulated in RGD-Modified Alginate Scaffold

Transient supplementation of growth factor TGF-β1 effectively initiates chondrogenic redifferentiation of human chondrocytes

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