A denatured collagen microfiber scaffold seeded with human fibroblasts and keratinocytes for skin grafting

Kempf, Margit; Miyamura, Yuichi; Liu, Pei-Yun; Chen, Alice C.‐H.; Nakamura, Hideki; Shimizu, Hiroshi; Tabata, Yasuhiko; Kimble, Roy M.; McMillan, James R.

doi:10.1016/j.biomaterials.2011.03.023

Cited by 84 publications

(56 citation statements)

References 35 publications

(54 reference statements)

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“…10,11 Electrospun nanofiber scaffolds, in particular, further permit control over nanofiber alignment to provide contact guidance to seeded cells. 12 In addition, it is easy to manipulate the macroscopic structure of these constructs for specific applications 13 and to encapsulate biomolecules [14][15][16][17] for a synergistic control over cell fate. To date, only few studies have demonstrated in vivo applications of electrospun synthetic nanofibers for nerve regeneration in the CNS.…”

mentioning

confidence: 99%

Nanofibrous Collagen Nerve Conduits for Spinal Cord Repair

Liu

Houlé

et al. 2012

Tissue Engineering Part A

131

105

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Nerve regeneration in an injured spinal cord is often restricted, contributing to the devastating outcome of neurologic impairment below the site of injury. Although implantation of tissue-engineered scaffolds has evolved as a potential treatment method, the outcomes remain sub-optimal. One possible reason may be the lack of topographical signals from these constructs to provide contact guidance to invading cells or regrowing axons. Nanofibers mimic the natural extracellular matrix architecturally and may therefore promote physiologically relevant cellular phenotypes. In this study, the potential application of electrospun collagen nanofibers (diameter = 208.2 -90.4 nm) for spinal cord injury (SCI) treatment was evaluated in vitro and in vivo. Primary rat astrocytes and dorsal root ganglias (DRGs) were seeded on collagen-coated glass cover slips (two-dimensional [2D] substrate controls), and randomly oriented or aligned collagen fibers to evaluate scaffold topographical effects on astrocyte behavior and neurite outgrowth, respectively. When cultured on collagen nanofibers, astrocyte proliferation and expression of glial fibrillary acidic protein (GFAP) were suppressed as compared to cells on 2D controls at days 3 ( p < 0.05) and 7 ( p < 0.01). Aligned fibers resulted in elongated astrocytes (elongation factor > 4, p < 0.01) and directed the orientation of neurite outgrowth from DRGs along fiber axes. In the contrast, neurites emanated radially on randomly oriented collagen fibers. By forming collagen scaffolds into spiral tubular structures, we demonstrated the feasibility of using electrospun nanofibers for the treatment of acute SCI using a rat hemi-section model. At days 10 and 30 postimplantation, extensive cellular penetration into the constructs was observed regardless of fiber orientation. However, scaffolds with aligned fibers appeared more structurally intact at day 30. ED1 immunofluorescent staining revealed macrophage invasion by day 10, which decreased significantly by day 30. Neural fiber sprouting as evaluated by neurofilament staining was observed as early as day 10. In addition, GFAP immunostained astrocytes were found only at the boundary of the lesion site, and no astrocyte accumulation was observed in the implantation area at any time point. These findings indicate the feasibility of fabricating 3D spiral constructs using electrospun collagen fibers and demonstrated the potential of these scaffolds for SCI repair.

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mentioning

confidence: 99%

Nanofibrous Collagen Nerve Conduits for Spinal Cord Repair

Liu

Houlé

et al. 2012

Tissue Engineering Part A

131

105

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“…33 Other studies have shown that when a collagen matrix with keratinocytes and fibroblasts is implanted in a full-thickness wound, the epidermal and dermal layers are present in the neoskin. 28,29,34 There is clearly room for improvement in existing skin grafts, and adding endothelial cells to a network is a step in this direction. There is some evidence that the addition of endothelial vessel networks will achieve viable integration.…”

Section: Discussionmentioning

confidence: 99%

In Vivo Assessment of Printed Microvasculature in a Bilayer Skin Graft to Treat Full-Thickness Wounds

Yanez

Rincon

Dones

et al. 2015

Tissue Engineering Part A

137

114

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Chronic wounds such as diabetic foot ulcers and venous leg ulcers are common problems in people suffering from type 2 diabetes. These can cause pain, and nerve damage, eventually leading to foot or leg amputation. These types of wounds are very difficult to treat and sometimes take months or even years to heal because of many possible complications during the process. Allogeneic skin grafting has been used to improve wound healing, but the majority of grafts do not survive several days after being implanted. We have been studying the behavior of fibroblasts and keratinocytes in engineered capillary-like endothelial networks. A dermo-epidermal graft has been implanted in an athymic nude mouse model to assess the integration with the host tissue as well as the wound healing process. To build these networks into a skin graft, a modified inkjet printer was used, which allowed the deposit of human microvascular endothelial cells. Neonatal human dermal fibroblast cells and neonatal human epidermal keratinocytes were manually mixed in the collagen matrix while endothelial cells printed. A full-thickness wound was created at the top of the back of athymic nude mice and the area was covered by the bilayered graft. Mice of the different groups were followed until completion of the specified experimental time line, at which time the animals were humanely euthanized and tissue samples were collected. Wound contraction improved by up to 10% when compared with the control groups. Histological analysis showed the neoskin having similar appearance to the normal skin. Both layers, dermis and epidermis, were present with thicknesses resembling normal skin. Immunohistochemistry analysis showed favorable results proving survival of the implanted cells, and confocal images showed the human cells' location in the samples that were collocated with the bilayer printed skin graft.

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“…The scaffold degrades by hydrolysis in 20-30 days while fibroblasts produce growth factors and ECM components (vitronectin, tenascin, collagens, and glycosaminoglycans), helping to reconstitute a dermal layer. The disadvantages of this product include a necessity for multiple applications, higher cost and safety issues owing to allogeneic cells incorporated into this bio construct [46].…”

Section: Cultured Neonatal Fibroblasts Grown On Different Scaffoldsmentioning

confidence: 99%

Advanced therapies of skin injuries

Maver

Stana‐Kleinschek

et al. 2015

Wien Klin Wochenschr

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The loss of tissue is still one of the most challenging problems in healthcare. Efficient laboratory expansion of skin tissue to reproduce the skins barrier function can make the difference between life and death for patients with extensive full-thickness burns, chronic wounds, or genetic disorders such as bullous conditions. This engineering has been initiated based on the acute need in the 1980s and today, tissue-engineered skin is the reality. The human skin equivalents are available not only as models for permeation and toxicity screening, but are frequently applied in vivo as clinical skin substitutes. This review aims to introduce the most important recent development in the extensive field of tissue engineering and to describe already approved, commercially available skin substitutes in clinical use.

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A denatured collagen microfiber scaffold seeded with human fibroblasts and keratinocytes for skin grafting

Cited by 84 publications

References 35 publications

Nanofibrous Collagen Nerve Conduits for Spinal Cord Repair

Nanofibrous Collagen Nerve Conduits for Spinal Cord Repair

In Vivo Assessment of Printed Microvasculature in a Bilayer Skin Graft to Treat Full-Thickness Wounds

Advanced therapies of skin injuries

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