Distinctive structure, composition and biomechanics of collagen fibrils in vaginal wall connective tissues associated with pelvic organ prolapse

Chi, Naiwei; Lozo, Svjetlana; Rathnayake, Rathnayake A C; Botros, Sylvia M.; Ma, Yin; Damaser, Margot S.; Wang, Rong R.

doi:10.1016/j.actbio.2022.08.059

Cited by 17 publications

(13 citation statements)

References 60 publications

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“…Collagen is the predominant structural protein in the tissues. Consistent with reports in the literature [ 14 , 15 , 16 ], reduced collagen content, increased collagen I (COLI) to collagen III (COLIII) ratio and abnormal nanoscopic to microscopic structures of fibrillar collagen in pelvic floor connective tissues of POP patients were observed in our previous studies [ 17 , 18 , 19 ]. These are closely relevant to the cellular deficit of patients’ fibroblasts, which synthesize collagen and relevant metabolites to regulate the structure and function of the fibrous matrix in connective tissues [ 10 , 14 , 16 ].…”

Section: Introductionsupporting

confidence: 93%

“…In an extracellular matrix, fibrillar COLI offers high tensile strength, whereas COLIII is found alongside COLI in tissues that require flexibility and distension [ 18 , 30 ]. A matrix with a high COLI/COLIII ratio, as in the case of collagen in prolapse patients’ pelvic floor connective tissues, is correlated with stiffer collagen fibers [ 19 ]. Grown on the stiff, aligned SF-CNT fibers, the fibroblasts responded to ES by synthesizing more COLIII than COLI to remodel the matrix and attain a softer substrate with reduced COLI/COLIII ratio ( Figure S3 ).…”

Section: Resultsmentioning

confidence: 99%

“…Fibroblasts of POP patients were characterized by reduced COLI and COLIII expression in comparison to that of non-POP individuals [ 6 ]. Additionally, the synthesized collagen is at an abnormally high COLI to COLIII ratio, leading to a loose and fragile collagen fiber network inadequate to support the pelvic organs [ 17 , 18 , 19 ]. The deficit fibroblasts are accountable for the connective tissue failure.…”

Section: Discussionmentioning

confidence: 99%

“…Concerns over high rates of complications, such as erosions, pain, infections, vaginal shrinkage, poor biocompatibility or lack of long-term effects undermined their usage. Additionally, the constructs provide physical support to relieve the stress of the local tissue and lift up the prolapsed organs, but do not rectify the aberrant biophysical and biochemical properties of collagen for tissue regeneration [ 19 ]. Availability of more management options and affordable treatments are highly desirable.…”

Section: Discussionmentioning

confidence: 99%

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Electrospun Silk Fibroin-CNT Composite Fibers: Characterization and Application in Mediating Fibroblast Stimulation

et al. 2022

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Electrospinning is a simple, low-cost, and highly efficient technique to generate desirable nano/microfibers from polymer solutions. Silk fibroin (SF), a biopolymer found in Bombyx mori cocoons, has attracted attention for various biomedical applications. In this study, functionalized CNT was incorporated in SF to generate biocomposite fibers by electrospinning. The electrospun (E-spun) fibers were well aligned with morphology mimicking the locally oriented ECM proteins in connective tissues. While as-spun fibers dissolved in water in just two minutes, ethanol vapor post-treatment promoted β-sheet formation leading to improved fiber stability in an aqueous environment (>14 days). The addition of a minute amount of CNT effectively improved the E-spun fiber alignment and mechanical strength while retained high biocompatibility and biodegradability. The fibers’ electrical conductivity increased by 13.7 folds and 21.8 folds, respectively, in the presence of 0.1 w% and 0.2 w% CNT in SF fibers. With aligned SF-CNT 0.1 % fibers as a cell culture matrix, we found electrical stimulation effectively activated fibroblasts from patients of pelvic organ prolapse (POP), a connective tissue disorder. The stimulation boosted the fibroblasts’ productivity of collagen III (COLIII) and collagen I (COLI) by 74 folds and 58 folds, respectively, and reduced the COLI to COLIII ratio favorable for tissue repair. The developed material and method offer a simple, direct, and effective way to remedy the dysfunctional fibroblasts of patients for personalized cell therapeutic treatment of diseases and health conditions associated with collagen disorder.

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Section: Introductionsupporting

confidence: 93%

Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Electrospun Silk Fibroin-CNT Composite Fibers: Characterization and Application in Mediating Fibroblast Stimulation

et al. 2022

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“…2 The fibroblast function in the vaginal connective tissue of POP patients is altered with impaired production and remodeling of collagen. 3,4 Studies report that the imbalance in collagen metabolism associates with changes in vaginal stiffness, suggesting an affected mechanical integrity of the tissue. 5−7 Stiffness is an important parameter in functional healing of vaginal connective tissue, not only as a contributor to being load bearing but also as a property of the vaginal fibroblast microenvironment.…”

Section: Introductionmentioning

confidence: 99%

Vaginal Fibroblast Behavior as a Function of Stiffness Changes in a Polyisocyanide Hydrogel for Prolapse Repair

Gudde,

van Velthoven,

Türkel

et al. 2023

ACS Appl. Bio Mater.

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There is an urgent need for improved outcomes in the treatment of pelvic organ prolapse (POP). Success of primary surgery relies on the load bearing capacity of plicated connective tissue underneath the vaginal wall, which is compromised due to an altered vaginal fibroblast function and collagen composition. There is an important factor in connective tissue repair that relates to changes in stiffness of the vaginal fibroblast microenvironment, which influences cell activity through cellular mechanosensing. The aim of this study is to investigate the effect of stiffness changes on vaginal fibroblast functions that relate to connective tissue healing in prolapse repair. The substrate stiffness was controlled by changing the polymer concentration in the fibrous and strongly biomimetic polyisocyanide (PIC) hydrogel. We analyzed stiffness during cell culture and assessed the consequential fibroblast proliferation, morphology, collagen deposition, and contraction. Our results show that increasing stiffness coincides with vaginal fibroblast alignment, promotes collagen deposition, and inhibits PIC gel contraction. These findings suggest that the matrix stiffness directly influences vaginal fibroblast functionality. Moreover, we observed a buildup in stiffness and collagen, with an enhanced fibroblast and collagen organization on the PIC-substrate, which indicate an enhanced structural integrity of the hydrogel-cell construct. An improved tissue structure during healing is relevant in the functional repair of POP. Therefore, this study encourages future research in the use of PIC gels as a supplement in prolapse surgery, whereby the hydrogel stiffness should be considered.

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Dual‐Crosslinked Bioactive Hydrogel Scaffold for Accelerated Repair of Genital Tract Defect

Wang,

Cheng,

Chen

et al. 2024

Adv Funct Materials

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Reproductive health concerns like Mayer‐Rokitansky‐Küster‐Hauser (MRKH) syndrome are prevalent in today's society. MRKH syndrome is a condition that severely affects women's sexual life, fertility, and mental health and has a high prevalence of one out of 5000 female births. Vaginoplasty is the primary method to regain patients’ reproductive health. However, conventional vaginoplasty faces various challenges, including complex and non‐customized treatment procedures causing intense pains and complications. To bring new advances to vaginoplasty, a 3D‐printed hydrogel scaffold is developed to provide satisfactory mechanical support and bioactivity for accelerating defect repair after surgery. The hydrogel scaffold consisting of gelatin methacryloyl (gelMA) and carrageenan (Car) is custom 3D‐printed using an ambient temperature printing system. Furthermore, the scaffold undergoes dual‐crosslinking through chemical crosslinking of gelMA and ionic crosslinking of Car with magnesium ions (Mg2+). This dual‐crosslinking strategy substantially improves the overall mechanical properties of the scaffold and introduces bioactive Mg2+. The sustained release of Mg2+ plus the extracts from the dual‐crosslinked scaffold significantly promotes cell proliferation, migration and angiogenesis. In a preclinical rat model with penetrating genital tract defects mimicking vaginoplasty, the implantation of dual‐crosslinked scaffold repairs the penetrating wounds to near‐normal levels within one week, showing potential as an alternative for better regaining reproductive health.

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Distinctive structure, composition and biomechanics of collagen fibrils in vaginal wall connective tissues associated with pelvic organ prolapse

Cited by 17 publications

References 60 publications

Electrospun Silk Fibroin-CNT Composite Fibers: Characterization and Application in Mediating Fibroblast Stimulation

Electrospun Silk Fibroin-CNT Composite Fibers: Characterization and Application in Mediating Fibroblast Stimulation

Vaginal Fibroblast Behavior as a Function of Stiffness Changes in a Polyisocyanide Hydrogel for Prolapse Repair

Dual‐Crosslinked Bioactive Hydrogel Scaffold for Accelerated Repair of Genital Tract Defect

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