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Arrayed Hollow Channels in Silk-based Scaffolds Provide Functional Outcomes for Engineering Critically-sized Tissue Constructs.

ABSTRACT: In the field of regenerative medicine there is a need for scaffolds that support large, critically-sized tissue formation. Major limitations in reaching this goal are the delivery of oxygen and nutrients throughout the bulk of the engineered tissue as well as host tissue integration and vascularization upon implantation. To address these limitations we previously reported the development of a porous scaffold platform made from biodegradable silk protein that contains an array of vascular-like structures that extend through the bulk of the scaffold. Here we report that the hollow channels play a pivotal role in enhancing cell infiltration, delivering oxygen and nutrients to the scaffold bulk, and promoting in vivo host tissue integration and vascularization. The unique features of this protein biomaterial system, including the vascular structures and tunable material properties, render this scaffold a robust and versatile tool for implementation in a variety of tissue engineering, regenerative medicine and disease modeling applications.

SUBMITTER: Rnjak-Kovacina J

PROVIDER: S-EPMC4225637 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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Arrayed Hollow Channels in Silk-based Scaffolds Provide Functional Outcomes for Engineering Critically-sized Tissue Constructs.

Rnjak-Kovacina Jelena J Wray Lindsay S LS Golinski Julianne M JM Kaplan David L DL

Advanced functional materials 20140401 15

In the field of regenerative medicine there is a need for scaffolds that support large, critically-sized tissue formation. Major limitations in reaching this goal are the delivery of oxygen and nutrients throughout the bulk of the engineered tissue as well as host tissue integration and vascularization upon implantation. To address these limitations we previously reported the development of a porous scaffold platform made from biodegradable silk protein that contains an array of vascular-like st ...[more]

PMID: 25395920

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Project description:Symptomatic osteoarthritic lesions span large regions of joint surfaces and the ability to engineer cartilage constructs at clinically relevant sizes would be highly desirable. We previously demonstrated that nutrient transport limitations can be mitigated by the introduction of channels in 10 mm diameter cartilage constructs. In this study, we scaled up our previous system to cast and cultivate 40 mm diameter constructs (2.3 mm overall thickness); 4 mm diameter and channeled 10 mm diameter constructs were studied for comparison. Furthermore, to assess whether prior results using primary bovine cells are applicable for passaged cells-a more clinically realistic scenario-we cast constructs of each size with primary or twice-passaged cells. Constructs were assessed mechanically for equilibrium compressive Young's modulus (EY), dynamic modulus at 0.01 Hz (G*), and friction coefficient (μ); they were also assessed biochemically, histologically, and immunohistochemically for glycosaminoglycan (GAG) and collagen contents. By maintaining open channels, we successfully cultured robust constructs the size of entire human articular cartilage layers (growing to ∼52 mm in diameter, 4 mm thick, mass of 8 g by day 56), representing a 100-fold increase in scale over our 4 mm diameter constructs, without compromising their functional properties. Large constructs reached EY of up to 623 kPa and GAG contents up to 8.9%/ww (% of wet weight), both within native cartilage ranges, had G* >2 MPa, and up to 3.5%/ww collagen. Constructs also exhibited some of the lowest μ reported for engineered cartilage (0.06-0.11). Passaged cells produced tissue of lower quality, but still exhibited native EY and GAG content, similar to their smaller controls. The constructs produced in this study are, to our knowledge, the largest engineered cartilage constructs to date which possess native EY and GAG, and are a testament to the effectiveness of nutrient channels in overcoming transport limitations in cartilage tissue engineering.

Dataset Information

Arrayed Hollow Channels in Silk-based Scaffolds Provide Functional Outcomes for Engineering Critically-sized Tissue Constructs.

Publications

Arrayed Hollow Channels in Silk-based Scaffolds Provide Functional Outcomes for Engineering Critically-sized Tissue Constructs.

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