Mitigation of hypertrophic scar contraction via an elastomeric biodegradable scaffold

Lorden, Elizabeth R.; Miller, Keith L.; Bashirov, Latif; Ibrahim, Mohamed M.; Hammett, Ellen; Jung, Youngmee; Medina, Manuel A.; Rastegarpour, Ali; Selim, M. Angélica; Leong, Kam W.; Levinson, Howard

doi:10.1016/j.biomaterials.2014.12.003

Cited by 56 publications

(63 citation statements)

References 55 publications

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“…However, ePCL in vivo degradation studies showed only 20-30% molecular weight reduction after 3-6 months, without structural deterioration [28–31]. Similarly, in our study, there was no significant degradation of the scaffold at explantation, and ePCL fibers could still been seen on histology.…”

Section: Discussionsupporting

confidence: 64%

“…A prior study suggested that the loss of architecture due to rapid degradation of the scaffold prior to the completion of tissue remodeling could impair cellular alignment and cause scar formation [28]. However, ePCL in vivo degradation studies showed only 20-30% molecular weight reduction after 3-6 months, without structural deterioration [28–31].…”

Section: Discussionmentioning

confidence: 99%

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Orthogonally oriented scaffolds with aligned fibers for engineering intestinal smooth muscle

Kobayashi

Wang

et al. 2015

Biomaterials

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Controlling cellular alignment is critical in engineering intestines with desired structure and function. Although previous studies have examined the directional alignment of cells on the surface (x-y plane) of parallel fibers, quantitative analysis of the cellular alignment inside implanted scaffolds with oriented fibers has not been reported. This study examined the cellular alignment in the x-z and y-z planes of scaffolds made with two layers of orthogonally oriented fibers. The cellular orientation inside implanted scaffolds was evaluated with immunofluorescence. Quantitative analysis of coherency between cell orientation and fiber direction confirmed that cells aligned along the fibers not only on the surface (x-y plane) but also inside the scaffolds (x-z & y-z planes). Our study demonstrated that two layers of orthogonally aligned scaffolds can generate the histological organization of cells similar to that of intestinal circular and longitudinal smooth muscle.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Orthogonally oriented scaffolds with aligned fibers for engineering intestinal smooth muscle

Kobayashi

Wang

et al. 2015

Biomaterials

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“…Scaffolds, whether biological or synthetic, offer the prospect of creating a favorable physical and chemical environment for tissue restoration. Scaffold pore size, morphology, and interconnectivity [52, 53] as well as the scaffold degradation rate [1, 54] can potentially reduce scar formation; however, the effects of substrate modulus on matrix deposition and alignment, angiogenesis, and macrophage phenotype have been less extensively investigated. Mechanical stress can have beneficial effects on cutaneous regeneration via enhanced proliferation, angiogenesis, and stem cell recruitment [55], but it also increases infiltration of inflammatory cells and decreases apoptosis of local cells involved in wound remodeling, both of which are major factors in tissue fibrosis and scarring [56].…”

Section: Discussionmentioning

confidence: 99%

“…While many studies have focused on the acceleration of wound closure, a growing number of studies have aimed to restore the function of impaired tissue through a more restorative wound approach [1]. Local delivery of recombinant human (rh) growth factors, such as platelet-derived growth factor (rhPDGF), transforming growth factor-β (rhTGF-β), and vascular endothelial growth factor (rhVEGF), from scaffolds has improved wound repair and restoration [2-4].…”

Section: Introductionmentioning

confidence: 99%

“…Three values of substrate modulus were investigated: 5 MPa (less rigid than a collagen fiber), 24 MPa (comparable to a collagen fiber (32 MPa [31])), and 266 MPa (more rigid than a collagen fiber). Previous studies have reported that regeneration is enhanced under conditions where (1) the bulk modulus of the scaffold ( K *) exceeds that of host dermal tissue (0.05 MPa) [32], and (2) the scaffold perists throughout all stages of the remodeling process [1]. In order to isolate the effects of substrate modulus on healing, t-FDM scaffolds with K * ≥ 0.5 MPa were fabricated using a slow-degrading polymer composition (5 – 10% mass loss at 3 weeks [33]).…”

Section: Introductionmentioning

confidence: 99%

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Substrate modulus of 3D-printed scaffolds regulates the regenerative response in subcutaneous implants through the macrophage phenotype and Wnt signaling

Merkel

Sterling

et al. 2015

Biomaterials

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The growing need for therapies to treat large cutaneous defects has driven recent interest in the design of scaffolds that stimulate regenerative wound healing. While many studies have investigated local delivery of biologics as a restorative approach, an increasing body of evidence highlights the contribution of the mechanical properties of implanted scaffolds to wound healing. In the present study, we designed poly(ester urethane) scaffolds using a templated-Fused Deposition Modeling (t-FDM) process to test the hypothesis that scaffolds with substrate modulus comparable to that of collagen fibers enhance a regenerative versus a fibrotic response. We fabricated t-FDM scaffolds with substrate moduli varying from 5 – 266 MPa to investigate the effects of substrate modulus on healing in a rat subcutaneous implant model. Angiogenesis, cellular infiltration, collagen deposition, and directional variance of collagen fibers were maximized for wounds treated with scaffolds having a substrate modulus (Ks = 24 MPa) comparable to that of collagen fibers. The enhanced regenerative response in these scaffolds was correlated with down-regulation of Wnt/β-catenin signaling in fibroblasts, as well as increased polarization of macrophages toward the restorative M2 phenotype. These observations highlight the substrate modulus of the scaffold as a key parameter regulating the regenerative versus scarring phenotype in wound healing. Our findings further point to the potential use of scaffolds with substrate moduli tuned to that of the native matrix as a therapeutic approach to improve cutaneous healing.

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Use of Elastic, Porous, and Ultrathin Co‐Culture Membranes to Control the Endothelial Barrier Function via Cell Alignment

Yoo

Kim

Park

et al. 2020

Adv Funct Materials

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Porous membranes used in co‐culture enable the in vitro partitioning of cellular microenvironments, while still permitting physical and biochemical crosstalk between cells. Thus, features of the co‐culture membrane are crucial for recapitulating the physiological functions of co‐cultured cells. This study presents elastic, porous, and ultrathin membranes (EPUMs), which enhance cell–cell interactions and control cell alignment with surface topology created by stretching the membranes. The EPUM is fabricated using poly(lactide‐co‐caprolactone) as the base material, and the porous feature is endowed by a vapor‐induced phase separation process induced by the presence of hygroscopic salt. Owing to its elastic property, the membrane can be stretched, and the deformed porous structures on the membrane surfaces act as nanostructured topographical cues, resulting in cell alignment. By co‐culturing human mesenchymal stem cells (hMSCs) and human umbilical vein endothelial cells (HUVECs) on the opposite sides of the membrane, rapid endothelialization occurs through the membranes, as compared to the commercial membranes. Furthermore, the stretched membranes induce the alignment of hMSCs and HUVECs and ultimately exhibit enhanced endothelial barrier function. The co‐culture membrane developed in this study may provide an effective tool for recapitulating endothelial basement membranes with a controllable endothelial barrier function.

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Mitigation of hypertrophic scar contraction via an elastomeric biodegradable scaffold

Cited by 56 publications

References 55 publications

Orthogonally oriented scaffolds with aligned fibers for engineering intestinal smooth muscle

Orthogonally oriented scaffolds with aligned fibers for engineering intestinal smooth muscle

Substrate modulus of 3D-printed scaffolds regulates the regenerative response in subcutaneous implants through the macrophage phenotype and Wnt signaling

Use of Elastic, Porous, and Ultrathin Co‐Culture Membranes to Control the Endothelial Barrier Function via Cell Alignment

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