Biocompatibility of Agarose Gel as a Dermal Filler: Histologic Evaluation of Subcutaneous Implants

Fernández-Cossío, Sergio; León-Mateos, A.; Sampedro, Francisco Gude; Oreja, María Teresa Castaño

doi:10.1097/01.prs.0000279475.99934.71

Cited by 55 publications

(54 citation statements)

References 34 publications

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“…In our current system, the polysaccharide agarose provides structural support to the hydrogel system and is used to facilitate harvesting of formed beads from the emulsification vessel. Agarose has been shown to be well integrated with host tissue in a rat dermal model; agarose gel was degraded and newly formed collagen fibers were visible in the implants with no noticeable granuloma formation 32. The need for a structural filler (e.g., alginate) in the production of collagen beads has been also reported in other bead formulation protocols 33,34.…”

Section: Discussionmentioning

confidence: 82%

Osteogenic differentiation of mesenchymal stem cells in defined protein beads

et al. 2008

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There is a need to develop improved methods for directing and maintaining the differentiation of human mesenchymal stem cells (hMSC) for regenerative medicine. Here, we present a method for embedding cells in defined protein microenvironments for the directed osteogenic differentiation of hMSC. Composite matrices of collagen I and agarose were produced by emulsification and simultaneous polymerization in the presence of hMSC to produce 30–150 μm diameter hydrogel “beads.” The proliferation, morphology, osteogenic gene expression, and calcium deposition of hMSC in bead environments were compared to other two- and three-dimensional culture environments over 14–21 days in culture. Cells embedded within 40% collagen beads exhibited equivalent proliferation rates to those in gel disks, but showed upregulation of bone sialoprotein and increased calcium deposition over 2D controls. Osteocalcin gene expression was not changed in 3D beads and disks, while collagen type I gene expression was downregulated relative to cells in 2D culture. The hydrogel bead format allows controlled cell differentiation and is a cell delivery vehicle that may also enhance vascular invasion and host incorporation. Our results indicate that the application of such beads can be used to promote the osteogenic phenotype in hMSC, which is an important step toward using them in bone repair applications.

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Section: Discussionmentioning

confidence: 82%

Osteogenic differentiation of mesenchymal stem cells in defined protein beads

et al. 2008

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“…Agarose has been previously shown to be biocompatible in long-term studies, and so was chosen here to provide support to the collagen-filled channels. 15,47 The BNIs were reproducibly prepared by a casting device that accommodates an external MicroRenathane Ò tube (Braintree Scientific, Inc; OD 3 mm, ID 1.75 mm, and length of 12 mm) and manually perforated to increase nutrient and gas exchange (250 lm perforations, every 1 mm on all sides of the tube). A brush made of metal fibers (250 and 500 lm diameter) was inserted through the tube into a ''loading well''.…”

Section: The Biosynthetic Nerve Implantmentioning

confidence: 99%

Peripheral Nerve Repair Through Multi-Luminal Biosynthetic Implants

et al. 2011

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Peripheral nerve damage is routinely repaired by autogenic nerve grafting, often leading to less than optimal functional recovery at the expense of healthy donor nerves. Alternative repair strategies use tubular scaffolds to guide the regeneration of damaged nerves, but despite the progress made on improved structural materials for the nerve tubes, functional recovery remains incomplete. We developed a biosynthetic nerve implant (BNI) consisting of a hydrogel-based transparent multichannel scaffold with luminar collagen matrix as a 3-D substrate for nerve repair. Using a rat sciatic nerve injury model we showed axonal regeneration through the BNI to be histologically comparable to the autologous nerve repair. At 10 weeks post-injury, nerve defects repaired with collagen-filled, single lumen tubes formed single nerve cables, while animals that received the multi-luminal BNIs showed multiple nerve cables and the formation of a perineurial-like layer within the available microchannels. Total numbers of myelinated and unmyelinated axons in the BNI were increased 3-fold and 30%, respectively, compared to collagen tubes. The recovery of reflexive movement confirmed the functional regeneration of both motor and sensory neurons. This study supports the use of multi-luminal BNIs as a viable alternative to autografts in the repair of nerve gap injuries.

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“…In vivo studies have demonstrated that agarose provides a microenvironment that supports the non-hypertrophic and non-proliferative chondrogenic phenotype [55]. The physiological response to agarose resembles a wound-healing response similar to other biomaterials commonly used in the context of tissue repair [56]. Studies in both animals and humans have shown that agarose can be completely biodegraded and cleared after implantation without adverse effects [55, 57].…”

Section: Introductionmentioning

confidence: 99%

Collagen Type II enhances chondrogenic differentiation in agarose-based modular microtissues

et al. 2016

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Background Cell-based therapies have made an impact on the treatment of osteoarthritis, however the repair and regeneration of thick cartilage defects is an important and growing clinical problem. Next-generation therapies that combine cells with biomaterials may provide improved outcomes. We have developed modular microenvironments that mimic the composition of articular cartilage as a delivery system for consistently differentiated cells. Methods Human bone marrow-derived mesenchymal stem cells (MSC) were embedded in modular microbeads consisting of agarose (AG) supplemented with 0%, 10%, and 20% collagen Type II (COL-II) using a water-in-oil emulsion technique. AG and AG/COL-II microbeads were characterized in terms of their structural integrity, size distribution, and protein content. The viability of embedded MSC and their ability to differentiate into osteogenic, adipogenic and chondrogenic lineages over three weeks in culture were also assessed. Results Microbeads made with <20% COL-II were robust, generally spheroidal in shape and 80 ± 10 µm in diameter. MSC viability in microbeads was consistently high over a week in culture, while viability in corresponding bulk hydrogels decreased with increasing COL-II content. Osteogenic differentiation of MSC was modestly supported in both AG and AG/COL-II microbeads, while adipogenic differentiation was strongly inhibited in COL-II containing microbeads. Chondrogenic differentiation of MSC was clearly promoted in microbeads containing COL-II, compared to pure AG matrices. Conclusions Inclusion of collagen Type II in agarose matrices in microbead format can potentiate chondrogenic differentiation of human MSC. Such compositionally tailored microtissues may find utility for cell delivery in next-generation cartilage repair therapies.

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Biocompatibility of Agarose Gel as a Dermal Filler: Histologic Evaluation of Subcutaneous Implants

Abstract: Agarose gel is a biocompatible product that can be considered for use as a tissue filler. Further investigation is required to assess its long-term efficacy and safety.

Cited by 55 publications

References 34 publications

Osteogenic differentiation of mesenchymal stem cells in defined protein beads

Osteogenic differentiation of mesenchymal stem cells in defined protein beads

Peripheral Nerve Repair Through Multi-Luminal Biosynthetic Implants

Collagen Type II enhances chondrogenic differentiation in agarose-based modular microtissues

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