Collagen-based substrates with tunable strength for soft tissue engineering

Kumar, Vivek; Caves, Jeffrey M.; Haller, Carolyn A.; Dai, Erbin; Li, Liying; Grainger, Stephanie; Chaikof, Elliot L.

doi:10.1039/c3bm60129c

Cited by 36 publications

(34 citation statements)

References 69 publications

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“…Understanding cellular interactions with collagen and the related overall mechanical behaviors of the cellularized collagen scaffolds (constructs) is an essential step for the construction of tissues. Collagen-based TEBVs can be processed by directly mixing cells with collagen during gel preparation and further molded into specific shapes such as tubular and planar 11 . Vascular cells inside the gels proliferate and remodel type I collagen 2 L/4 and A = D in L respectively (where D in is the inner diameter corresponding to the mandrel diameter, and L is the length of the construct).…”

Section: Introductionmentioning

confidence: 99%

Engineering 3D Cellularized Collagen Gels for Vascular Tissue Regeneration

Meghezi

Seifu

Bono

et al. 2015

JoVE

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Synthetic materials are known to initiate clinical complications such as inflammation, stenosis, and infections when implanted as vascular substitutes. Collagen has been extensively used for a wide range of biomedical applications and is considered a valid alternative to synthetic materials due to its inherent biocompatibility (i.e., low antigenicity, inflammation, and cytotoxic responses). However, the limited mechanical properties and the related low hand-ability of collagen gels have hampered their use as scaffold materials for vascular tissue engineering. Therefore, the rationale behind this work was first to engineer cellularized collagen gels into a tubular-shaped geometry and second to enhance smooth muscle cells driven reorganization of collagen matrix to obtain tissues stiff enough to be handled.The strategy described here is based on the direct assembling of collagen and smooth muscle cells (construct) in a 3D cylindrical geometry with the use of a molding technique. This process requires a maturation period, during which the constructs are cultured in a bioreactor under static conditions (without applied external dynamic mechanical constraints) for 1 or 2 weeks. The "static bioreactor" provides a monitored and controlled sterile environment (pH, temperature, gas exchange, nutrient supply and waste removal) to the constructs. During culture period, thickness measurements were performed to evaluate the cells-driven remodeling of the collagen matrix, and glucose consumption and lactate production rates were measured to monitor the cells metabolic activity. Finally, mechanical and viscoelastic properties were assessed for the resulting tubular constructs. To this end, specific protocols and a focused know-how (manipulation, gripping, working in hydrated environment, and so on) were developed to characterize the engineered tissues.

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Section: Introductionmentioning

confidence: 99%

Engineering 3D Cellularized Collagen Gels for Vascular Tissue Regeneration

Meghezi

Seifu

Bono

et al. 2015

JoVE

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“…Several technologies aim to mimic this by electrospinning [29, 30], utilizing nanofibrous scaffolds [31] and using biological naturally derived or reconstituted matrices [32]. However several drawbacks, such as potential acidic by-products of degradation or non-natural monomers, immune rejection, lack of mechanical tunability or loss of native structure of reconstituted biological polymers may cause adverse responses in vivo [2–4, 18, 30]. We have consequently chosen to use reconstituted collagen materials with high strength and tunable mechanical properties that are processed to maintain native structure, and fabricated to yield mechanical and structural anisotropy.…”

Section: Resultsmentioning

confidence: 99%

Microablation of collagen-based substrates for soft tissue engineering

et al. 2014

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Noting the abundance and importance of collagen as a biomaterial, we have developed a facile method for the production of dense fibrillar extracellular matrix mimicking collagen-elastin hybrids with tunable mechanical properties. Through the use of excimer laser technology, we have optimized conditions for the ablation of collagen lamellae without denaturation of protein, maintenance of fibrillar ultrastructure and preservation of native D-periodicity. Strengths of collagen-elastin hybrids ranged from 0.6 - 13 MPa, elongation at break from 9 - 70 %, and stiffness from 2.9 - 94 MPa, allowing for the design of a wide variety of tissue specific scaffolds. Further, large (centimeter scale) lamellae can be fabricated and embedded with recombinant elastin to generate collagen-elastin hybrids. Exposed collagen in hybrids act as cell adhesive sites for rat mesenchymal stem cells that conform to ablate waveforms. The ability to modulate these features allows for the generation of a class of biopolymers that can architecturally and physiologically replicate native tissue.

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“…As an alternative, multiple groups have sought to use purified monomeric collagen, as a building block for engineering more complex materials due to its capacity support cell adhesion, proliferation, and differentiation. Collagen based products, including fibers and single or multilamellar sheets or tubes can be fabricated with precise control over physical and mechanical properties [23, 31] [13]. …”

Section: Discussionmentioning

confidence: 99%

“…Recently, control over collagen processing has provided new opportunities to design and fabricate synthetic ECM constructs for tissue reconstruction [13]. Significantly, high-density collagen constructs can be designed that display slower degradation, tunable strength and flexibility, and can be modified for the delivery of therapeutics or cells.…”

Section: Introductionmentioning

confidence: 99%

Engineered composite fascia for stem cell therapy in tissue repair applications

et al. 2015

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A critical challenge in tissue regeneration is to develop constructs that effectively integrate with the host tissue. Here, we describe a composite, laser micromachined, collagen-alginate construct containing human mesenchymal stem cells (hMSCs) for tissue repair applications. Collagen type I was fashioned into laminated collagen sheets to form a mechanically robust fascia that was subsequently laser micropatterned with pores of defined dimension and spatial distribution as a means to modulate mechanical behavior and promote tissue integration. Significantly, laser micromachined patterned constructs displayed both substantially greater compliance and suture retention strength than non-patterned constructs. hMSCs were loaded in an RGD-functionalized alginate gel modified to degrade in vivo. Over a 7 day observation period in vitro, high cell viability was observed with constant levels of VEGF, PDGF-β and MCP-1 protein expression. In a full thickness abdominal wall defect model, the composite construct prevented hernia recurrence in Wistar rats over an 8-week period with de novo tissue and vascular network formation and the absence of adhesions to underlying abdominal viscera. As compared to acellular constructs, constructs containing hMSCs displayed greater integration strength (cell seeded: 0.92 ± 0.19 N/mm vs. acellular: 0.59 ± 0.25 N/mm, p = 0.01), increased vascularization (cell seeded: 2.7–2.1/hpf vs. acellular: 1.7–2.1/hpf, p < 0.03), and increased infiltration of macrophages (cell seeded: 2021–3630 µm2/hpf vs. acellular: 1570–2530 µm2/hpf, p < 0.05). A decrease in the ratio of M1 macrophages to total macrophages was also observed in hMSC-populated samples. Laser micromachined collagen-alginate composites containing hMSCs can be used to bridge soft tissue defects with the capacity for enhanced tissue repair and integration.

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Collagen-based substrates with tunable strength for soft tissue engineering

Cited by 36 publications

References 69 publications

Engineering 3D Cellularized Collagen Gels for Vascular Tissue Regeneration

Engineering 3D Cellularized Collagen Gels for Vascular Tissue Regeneration

Microablation of collagen-based substrates for soft tissue engineering

Engineered composite fascia for stem cell therapy in tissue repair applications

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