Construction of a Microstructured Collagen Membrane Mimicking the Papillary Dermis Architecture and Guiding Keratinocyte Morphology and Gene Expression

Lammers, Gerwen; Roth, Günter; Heck, M.; Zengerle, Roland; Tjabringa, Geuranne S.; Versteeg, E.M.M.; Hafmans, T.G.M.; Wismans, Ronnie G.; Reinhardt, Dieter P.; Verwiel, Eugène; Zeeuwen, Patrick L.J.M.; Schalkwijk, Joost; Brock, Roland; Daamen, Willeke F.; Kuppevelt, Toin H. Van

doi:10.1002/mabi.201100443

Cited by 27 publications

(15 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Later, Watt et al examined stem cell patterning in the IF epidermis by correlating the regional variation in integrin expression levels in human skin with the colony forming efficiency of keratinocytes [12, 17–19]. Additionally, a recent study of keratinocytes seeded on a microfabricated dermal papilla template showed differential gene expression on micropatterned membranes compared to flat controls [27]. Given the continued lack of understanding of the role of microtopography in directing cellular phenotype, function and fate, we suggest that the topography of the dermal-epidermal junction is largely responsible for driving the clustering of these keratinocyte sub-populations and hypothesize that topographical cues can be used to direct keratinocyte phenotype and create stem cell reservoirs.…”

Section: Introductionmentioning

confidence: 99%

Micropatterned dermal–epidermal regeneration matrices create functional niches that enhance epidermal morphogenesis

2013

View full text Add to dashboard Cite

Although tissue engineered skin substitutes have demonstrated some clinical success for the treatment of chronic wounds such as diabetic and venous ulcers, persistent graft take and stability remain concerns. Current bilayered skin substitutes lack the characteristic microtopography of the dermal-epidermal junction that gives skin enhanced mechanical stability and creates cellular microniches that differentially promote keratinocyte function to form skin appendages and enhance wound healing. We developed a novel micropatterned dermal-epidermal regeneration matrix (μDERM) which incorporates this complex topography and substantially enhances epidermal morphology. Here, we describe the use of this 3D in vitro culture model to systematically evaluate different topographical geometries, to determine their relationship to keratinocyte function. We identified three distinct keratinocyte functional niches: the proliferative niche (narrow geometries), the basement membrane protein synthesis niche (wide geometries) and the putative keratinocyte stem cell niche (narrow geometries and corners). Specifically, epidermal thickness and keratinocyte proliferation is significantly (p<0.05) increased in 50 and 100 μm channels while laminin-332 deposition is significantly (p<0.05) increased in 400 μm channels compared to flat controls. Additionally, β1brip63+ keratinocytes, putative keratinocyte stem cells, preferentially cluster in channel geometries (similar to clustering observed in native skin) compared to a random distribution on flats. This study identifies specific target geometries to enhance skin regeneration and graft performance. Furthermore, these results suggest the importance of μDERM microtopography in designing next generation skin substitutes. Finally, we anticipate that 3D organotypic cultures on μDERMS will provide a novel tissue engineered skin substitute for in vitro investigations of skin morphogenesis, wound healing and pathology.

show abstract

Section: Introductionmentioning

confidence: 99%

Micropatterned dermal–epidermal regeneration matrices create functional niches that enhance epidermal morphogenesis

2013

View full text Add to dashboard Cite

show abstract

“…In the epidermis, the specific architecture of the rete ridges provides a mechanical niche for keratinocytes. This knowledge may be used in TE/RM, as in constructs with an architecture comparable to this rete ridge structure the epithelialization rate was higher than in constructs with a flat surface, and the expression of genes related to proliferation and migration was increased in keratinocytes . Mechanical strain has further been found to increase the proliferation of keratinocytes by both static and cyclic stretch, whereas differentiation was down‐regulated by static stretch .…”

Section: Mechanical Strain In Te/rm Of Orofacial Skin and Mucosamentioning

confidence: 98%

“…This knowledge may be used in TE/RM, as in constructs with an architecture comparable to this rete ridge structure the epithelialization rate was higher than in constructs with a flat surface, and the expression of genes related to proliferation and migration was increased in keratinocytes. [124][125][126] Mechanical strain has further been found to increase the proliferation of keratinocytes by both static and cyclic stretch, 38,40 whereas differentiation was down-regulated by static stretch. 40 Keratinocyte proliferation may be beneficial in the closure of wounds but can also cause a thickened epidermis as observed in hypertrophic scars and psoriasis.…”

Section: Mechanical Strain In Te/rm Of Orofacial Skin and Mucosamentioning

confidence: 99%

Mechanical cues in orofacial tissue engineering and regenerative medicine

Brouwer

Lundvig

Middelkoop

et al. 2015

Wound Repair Regeneration

View full text Add to dashboard Cite

Cleft lip and palate patients suffer from functional, aesthetical, and psychosocial problems due to suboptimal regeneration of skin, mucosa, and skeletal muscle after restorative cleft surgery. The field of tissue engineering and regenerative medicine (TE/RM) aims to restore the normal physiology of tissues and organs in conditions such as birth defects or after injury. A crucial factor in cell differentiation, tissue formation, and tissue function is mechanical strain. Regardless of this, mechanical cues are not yet widely used in TE/RM. The effects of mechanical stimulation on cells are not straight-forward in vitro as cellular responses may differ with cell type and loading regime, complicating the translation to a therapeutic protocol. We here give an overview of the different types of mechanical strain that act on cells and tissues and discuss the effects on muscle, and skin and mucosa. We conclude that presently, sufficient knowledge is lacking to reproducibly implement external mechanical loading in TE/RM approaches. Mechanical cues can be applied in TE/RM by fine-tuning the stiffness and architecture of the constructs to guide the differentiation of the seeded cells or the invading surrounding cells. This may already improve the treatment of orofacial clefts and other disorders affecting soft tissues.

show abstract

“…It has been widely applied in skin, nerves, heart, ocular, bone and cartilage tissue engineering [65][66][67][68].…”

Section: Tissue Regeneration and Engineeringmentioning

confidence: 99%

Chondroitin Sulfate as a Bioactive Macromolecule for Advanced Biological Applications and Therapies

Volpi

2016

Biomaterials From Nature for Advanced Devices and Therapies

View full text Add to dashboard Cite

Construction of a Microstructured Collagen Membrane Mimicking the Papillary Dermis Architecture and Guiding Keratinocyte Morphology and Gene Expression

Cited by 27 publications

References 40 publications

Micropatterned dermal–epidermal regeneration matrices create functional niches that enhance epidermal morphogenesis

Micropatterned dermal–epidermal regeneration matrices create functional niches that enhance epidermal morphogenesis

Mechanical cues in orofacial tissue engineering and regenerative medicine

Chondroitin Sulfate as a Bioactive Macromolecule for Advanced Biological Applications and Therapies

Contact Info

Product

Resources

About