The impact of bacterial contamination on the host response towards fully absorbable poly-4-hydroxybutyrate and nonabsorbable polypropylene pelvic floor implants

Verhorstert, Kim W.J.; Riool, Martijn; Bulten, Tess; Güler, Zeliha; Boer, Leonie de; Roovers, Jan‐Paul W. R.; Zaat, Sebastian A. J.

doi:10.1016/j.mtbio.2022.100268

Cited by 5 publications

(4 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…For the current study, we produced our own absorbable electrospun P4HB scaffolds. P4HB was chosen as knitted P4HB implants have shown promise in reconstructive surgery for ventral hernia repair and in our preclinical studies for pelvic floor repair. ,,, In addition, electrospun P4HB for other applications such as a dural or dermal , substitution are encouraging, but the available studies are limited, and no studies on electrospun P4HB for pelvic floor repair have been conducted. Because fibroblasts are the main cell type of the connective tissue of the vaginal wall and are responsible for maintaining the ECM, , their function is critical in assessing implant performance in the pelvic floor and to predict how the implant will interact with the host.…”

Section: Discussionmentioning

confidence: 99%

Absorbable Electrospun Poly-4-hydroxybutyrate Scaffolds as a Potential Solution for Pelvic Organ Prolapse Surgery

Verhorstert

Gudde

Weitsz

et al. 2022

ACS Appl. Bio Mater.

Self Cite

View full text Add to dashboard Cite

Women with pelvic organ prolapse (POP) have bothersome complaints that significantly affect their quality of life. While native tissue repair is associated with high recurrence rates, polypropylene knitted implants have caused specific implant-related adverse events that have detrimental, often irreversible, effects. We hypothesize that surgical outcome can be improved with a tissue-engineered solution using an absorbable implant that mimics the natural extracellular matrix (ECM) structure, releases estrogen, and activates collagen metabolism by fibroblasts as the main regulators of wound healing. To this aim, we produced electrospun poly-4-hydroxybutyrate (P4HB) scaffolds and biofunctionalized them with estradiol (E2). The cell–implant interactions relevant for POP repair were assessed by seeding primary POP vaginal fibroblasts isolated from patients on electrospun P4HB scaffolds with 1%, 2%, or 5% E2 and without E2. To test our hypothesis on whether ECM mimicking structures should improve regeneration, electrospun P4HB was compared to knitted P4HB implants. We evaluated vaginal fibroblast proliferation, ECM deposition, and metabolism by quantification of collagen, elastin, and matrix metalloproteinases and by gene expression analysis for 28 days. We established effective E2 drug loading with a steady release over time. Significantly higher cell proliferation, collagen-, and elastin deposition were observed on electrospun P4HB scaffolds as compared to knitted P4HB. For this study, physical properties of the scaffolds were more determinant on the cell response than the release of E2. These results indicate that making these electrospun P4HB scaffolds E2-releasing appears to be technically feasible. In addition, electrospun P4HB scaffolds promote the cellular response of vaginal fibroblasts and further studies are merited to assess if their use results in improved surgical outcomes in case of POP repair.

show abstract

Section: Discussionmentioning

confidence: 99%

Absorbable Electrospun Poly-4-hydroxybutyrate Scaffolds as a Potential Solution for Pelvic Organ Prolapse Surgery

Verhorstert

Gudde

Weitsz

et al. 2022

ACS Appl. Bio Mater.

Self Cite

View full text Add to dashboard Cite

show abstract

“… 8 , 40 , 46 − 48 Implantation of P4HB in a subcutaneous rat model showed a host response to the implant compared to sham surgery. 49 In a sheep model, the host response was moderate, with good tissue integration and dense connective tissue, following vaginal implantation of P4HB. 14 Although these results are promising, further evaluation in a more complex in vivo environment of an animal model should determine if the ECM remodeling on the VVF implant is well-balanced and results in functional healing.…”

Section: Discussionmentioning

confidence: 97%

“…A meta-analysis on the application of AM in reconstructive surgery showed no or a minimal foreign body response, low inflammation scores, and good epithelialization when the AM was applied in different human and animal models . This is supported by preclinical research that shows that AM exhibits anti-inflammatory, − immunosuppressive, − antifibrotic, , antimicrobial, and immunomodulatory properties. ,,− Implantation of P4HB in a subcutaneous rat model showed a host response to the implant compared to sham surgery . In a sheep model, the host response was moderate, with good tissue integration and dense connective tissue, following vaginal implantation of P4HB .…”

Section: Discussionmentioning

confidence: 99%

The Regenerative Capacity of Tissue-Engineered Amniotic Membranes

Maljaars,

Gudde,

Oosthuysen

et al. 2024

ACS Appl. Bio Mater.

Self Cite

View full text Add to dashboard Cite

Scaffolds can be introduced as a source of tissue in reconstructive surgery and can help to improve wound healing. Amniotic membranes (AMs) as scaffolds for tissue engineering have emerged as promising biomaterials for surgical reconstruction due to their regenerative capacity, biocompatibility, gradual degradability, and availability. They also promote fetal-like scarless healing and provide a bioactive matrix that stimulates cell adhesion, migration, and proliferation. The aim of this study was to create a tissue-engineered AM-based implant for the repair of vesicovaginal fistula (VVF), a defect between the bladder and vagina caused by prolonged obstructed labor. Layers of AMs (with or without cross-linking) and electrospun poly-4-hydroxybutyrate (P4HB) (a synthetic, degradable polymer) scaffold were joined together by fibrin glue to produce a multilayer scaffold. Human vaginal fibroblasts were seeded on the different constructs and cultured for 28 days. Cell proliferation, cell morphology, collagen deposition, and metabolism measured by matrix metalloproteinase (MMP) activity were evaluated. Vaginal fibroblasts proliferated and were metabolically active on the different constructs, producing a distributed layer of collagen and proMMP-2. Cell proliferation and the amount of produced collagen were similar across different groups, indicating that the different AM-based constructs support vaginal fibroblast function. Cell morphology and collagen images showed slightly better alignment and organization on the un-cross-linked constructs compared to the cross-linked constructs. It was concluded that the regenerative capacity of AM does not seem to be affected by mechanical reinforcement with cross-linking or the addition of P4HB and fibrin glue. An AM-based implant for surgical repair of internal organs requiring load-bearing functionality can be directly translated to other types of surgical reconstruction of internal organs.

show abstract

“…Gross anatomical examination of the explanted vagina was performed using the following parameters for implant-related complications: fluid collection, exposure of the implant, synechiae, and signs of infection. Exposure is defined as a mesh that is visible through the vaginal epithelium [ 20 , 21 ]. Vaginal explants (vaginal tissue/implant complex) were dissected into four pieces for assessing passive biomechanical properties, histomorphology, in vivo degradation (only for P4HB), and SEM images.…”

Section: Methodsmentioning

confidence: 99%

Two-Year Preclinical Evaluation of Long-Term Absorbable Poly-4-hydroxybutyrate Scaffold for Surgical Correction of Pelvic Organ Prolapse

Guler,

Kaestner,

Vodegel

et al. 2024

Int Urogynecol J

Self Cite

View full text Add to dashboard Cite

Introduction and hypothesis Fully absorbable implants may be an alternative to permanent meshes in the correction pf pelvic organ prolapse (POP) as they may reduce adverse events by promoting tissue regeneration and collagen metabolism. This study was aimed at evaluating the long-term host and biomechanical response to a fully absorbable poly-4-hydroxybutyrate (P4HB) scaffold in comparison with polypropylene (PP) mesh. Methods Poly-4-hydroxybutyrate scaffold (n = 16) and PP mesh (n = 16) were surgically implanted in the posterior vaginal wall of parous female Dohne Merino sheep. Vaginal explants were evaluated in terms of gross necropsy, host response (immune response, collagen deposition, tissue regeneration), biomechanics, and degradation of P4HB at 12 and 24 months post-implantation. Results Gross necropsy revealed no infection or fluid collection using P4HB or PP. At 12 months, exposures were observed with both P4HB (3 out of 8) and PP (4 out of 8), whereas at 24 months, exposures were observed only with PP (4 out of 8). The tensile stiffness of the P4HB explants was maintained over time despite complete absorption of P4HB. The collagen amount of the vaginal tissue after P4HB implantation increased over time and was significantly higher than PP at 24 months. P4HB scaffolds exhibited significantly lower myofibroblast differentiation than PP meshes at 24 months. Conclusions The P4HB scaffold allowed for gradual load transfer to the vaginal wall and resulted in mechanically self-sufficient tissue. P4HB scaffold had a more favorable host response than PP mesh, with higher collagen content, lower myofibroblastic differentiation, and no exposures at 24 months. P4HB scaffolds have potential as an alternative to permanent implants in treating POP.

show abstract

The impact of bacterial contamination on the host response towards fully absorbable poly-4-hydroxybutyrate and nonabsorbable polypropylene pelvic floor implants

Cited by 5 publications

References 48 publications

Absorbable Electrospun Poly-4-hydroxybutyrate Scaffolds as a Potential Solution for Pelvic Organ Prolapse Surgery

Absorbable Electrospun Poly-4-hydroxybutyrate Scaffolds as a Potential Solution for Pelvic Organ Prolapse Surgery

The Regenerative Capacity of Tissue-Engineered Amniotic Membranes

Two-Year Preclinical Evaluation of Long-Term Absorbable Poly-4-hydroxybutyrate Scaffold for Surgical Correction of Pelvic Organ Prolapse

Contact Info

Product

Resources

About