Melt Electrowritten Biodegradable Mesh Implants with Auxetic Designs for Pelvic Organ Prolapse Repair

Abstract

Pelvic organ prolapse (POP) is a common condition among women, characterized by the descent of pelvic organs through the vaginal canal. Although traditional synthetic meshes are widely utilized, they are associated with complications such as erosion, infection, and tissue rejection. This study explores the design and fabrication of biodegradable auxetic implants using polycaprolactone and melt electrowriting technology, with the goal of developing implants that closely replicate the mechanical behavior of vaginal tissue while minimizing implant-related complications. Four distinct auxetic mesh geometries—re-entrant Evans, Lozenge grid, square grid, and three-star honeycomb—were fabricated with a 160 $\mathrm{\mu }$m diameter and mechanically evaluated through uniaxial tensile testing. The results indicate that the square grid and three-star honeycomb geometries exhibit hyperelastic-like behavior, closely mimicking the stress–strain response of vaginal tissue. The re-entrant Evans geometry has been observed to exhibit excessive stiffness for applications related to POP, primarily due to material overlap. This geometry demonstrates stiffness that is approximately five times greater than that of the square grid or the three-star honeycomb configurations, which contributes to an increase in local rigidity. The unique auxetic properties of these structures prevent the bundling effect observed in synthetic meshes, promoting improved load distribution and minimizing the risk of tissue compression. Additionally, increasing the extrusion diameter has been identified as a promising strategy for further refining the biomechanical properties of these meshes. These findings lay a solid foundation for the development of next-generation biodegradable implants.

1. Introduction

Advancements in medical research and biomedical engineering have significantly contributed to increasing human lifespans and improving quality of life. As the population ages, organ dysfunction and tissue degeneration become more prevalent. This increased prevalence necessitates innovative solutions for tissue repair and regeneration. Pelvic organ prolapse (POP) is a prevalent condition primarily affecting women who have gone through menopause, with the highest occurrence between the ages of 60 and 69 years [1]. This condition involves the displacement of one or more pelvic organs (such as the uterus, bladder, and/or rectum) from their normal anatomical position into the vaginal canal [2]. Figure 1 illustrates the incremental descent of the uterus.

There is no universally accepted surgical method for these situations. Native tissue repairs have a high recurrence rate of 16% to 29%, along with complications such as erosion, infection, and chronic pain [3]. Due to the complications associated with synthetic mesh implants, the FDA banned certain transvaginal synthetic meshes in 2019 [4]. Biodegradable meshes have been developed to address these challenges. They function as temporary scaffolds, supporting tissue regeneration and minimizing long-term complications associated with permanent implants. Research has shown the efficacy of synthetic materials in procedures such as abdominal prolapse repair and suburethral sling placements. However, their success in transvaginal applications remains uncertain, as there is a lack of comprehensive randomized clinical trials to evaluate their long-term safety and effectiveness in this setting thoroughly.

In the field of tissue engineering, synthetic and biologically derived meshes play a critical role in restoring damaged tissues and organs by providing structural support and facilitating cell growth and tissue integration [5]. Polycaprolactone (PCL) is a widely studied biodegradable polymer recognized for its biocompatibility, adjustable mechanical properties, and controlled degradation rate [6,7,8,9]. Due to these characteristics, along with its FDA approval for medical applications, PCL has emerged as a promising candidate for pelvic floor reconstruction [10,11]. With a melting point ranging from 59 to 64 °C and a glass transition temperature of −60 °C, PCL is well suited for 3D printing and polymer blending, allowing for the management of the degradation period [12]. PCL degrades through hydrolysis and microbial action, exhibiting a prolonged degradation time frame of 2 to 3 years compared to other polyesters such as PGA and PLLA [11].

Various fabrication methods are utilized to produce PCL scaffolds, including solvent casting, porogen leaching, electrospinning, and 3D printing. Among these techniques, electrospinning is acknowledged as the most effective for generating ultra-fine fibers and three-dimensional scaffolds, while 3D printing allows for precise design and the controlled placement of biomaterials [13]. Recent advancements have showcased the potential of PCL composites, such as PCL/hydroxyapatite scaffolds for bone regeneration, thereby expanding its applications within the biomedical field [12,14].

Melt electrowriting (MEW) technology has emerged as a promising technique for fabricating highly controlled, micro-scale polymeric structures that closely mimic the extracellular matrix of native tissues [15]. This technology has gained significant attention in medical research, particularly in tissue engineering, biomedical engineering, and biotechnology. The MEW technique provides exact control over the fiber diameter, porosity, and scaffold design. The optimal mesh should be biocompatible, long-lasting, resistant to infection and shrinkage, and capable of restoring normal anatomy and functionality [16]. With the advent of MEW technology, it is now possible to fabricate PCL-based scaffolds with customized geometries that enhance mechanical performance and promote cellular interactions [6]. These scaffolds are emerging as a viable alternative to traditional synthetic meshes [8]. Research has indicated that MEW-based PCL meshes can simulate the behavior of vaginal tissue, positioning them as a promising option for the treatment of POP. MEW is preferred over techniques like electrospinning and conventional extrusion-based 3D printing for producing precise and mechanically stable mesh implants for POP repair. It offers better stability and control in fiber deposition, resulting in more consistent scaffold architecture. Additionally, MEW can create much thinner fibers, closely mimicking the native vaginal tissue’s mechanical properties. However, MEW faces challenges with slower fabrication speeds, which may limit large-scale production.

Knitted meshes remain the predominant choice for surgical implants in POP repair; however, their implementation is frequently accompanied by graft-related complications. To mitigate these challenges, innovative mesh designs that incorporate microscale fibers have been posited to enhance cell attachment and facilitate tissue integration [17]. The bundling effect, frequently observed in traditional knitted and woven meshes, occurs when fibers gradually engage under tensile load, resulting in localized stiffening and the uneven distribution of forces. This phenomenon can lead to tissue erosion, chronic inflammation, and foreign-body reactions, as excessive mechanical stress is concentrated on small areas of the surrounding tissue [18].

A promising solution to mitigating this issue involves the use of auxetic scaffolds—structures characterized by a negative Poisson’s ratio, which display unique mechanical properties such as transverse expansion under axial tension. These properties facilitate superior adaptability, durability, and enhanced cellular integration in comparison to conventional scaffolds [15]. Auxetic behavior has been observed in various biological tissues, including skin, cancellous bone, arteries, tendons, and the intervertebral disk annulus fibrosus. The natural auxeticity of these tissues contributes to their mechanical resilience and ability to withstand physiological loads [19,20,21]. Inspired by these biological structures, researchers have explored the development of auxetic scaffolds for biomedical applications, including bio-prostheses, stents, and orthopedic implants [15].

MEW enables the precise manufacturing of auxetic PCL-based scaffolds, which have shown promise in soft tissue engineering, particularly in the treatment of POP [15]. These engineered scaffolds closely replicate the mechanical properties of vaginal tissue, offering a potential alternative to traditional synthetic meshes. Despite their potential, auxetic scaffolds pose challenges in design and fabrication due to their complex geometries. Studies indicate that variations in aspect ratio significantly influence the mechanical behavior of these structures, necessitating precise control over scaffold architecture to achieve optimal biomechanical performance [22].

This study aimed to develop novel mesh geometries with an auxetic design, including four distinct auxetic patterns: re-entrant Evans, lozenge grid, square grid, and three-star honeycomb. These meshes were subsequently fabricated using PCL through the MEW technique. Mechanical characterization, including uniaxial tensile tests, was conducted. Additionally, mechanical testing of sow vaginal tissue was performed to compare the load-strain behavior of the auxetic meshes with that of the biological tissue.

2. Materials and Methods

2.1. Printing Machine and PCL

The MEW prototype, developed under the SPINMESH project funded by the Foundation for Science and Technology (FCT), features a modular design that integrates components like structural support, control systems, motion mechanisms, and a high-voltage generator (60 kV–150 W, minimum output current of 0.01 mA) [8]. It employs an XY-moving collector and Z-moving print head, allowing a maximum height of 70 mm. The collector plate, made of 3 mm-thick aluminum and measuring 270 × 270 mm², ensures stability during printing, with a positive voltage applied to the collector and negative to the nozzle for controlled fiber deposition [9].

The melt electrowriting machine was modified to include a heated print bed Figure 2 to improve both printing quality and the structural integrity of fabricated meshes. This enhancement optimizes filament fusion and strengthens inter-fiber bonding. Maintaining an ideal bed temperature keeps the deposited PCL fibers partially molten upon contact, improving adhesion between layers and individual filaments. This modification significantly minimizes the risk of fiber detachment, resulting in mechanically stable and uniform meshes, which is particularly advantageous for biodegradable implants that demand structural integrity.

In this study, the biodegradable PCL filament, Facilan^TM from 3D4Makers, was used. It has a density of 1.1 g/cm³ and a diameter of 1.75 mm, with a printing temperature range of 130 °C to 170 °C and a bed temperature of 30 °C to 45 °C. With a tensile strength of 45 MPa and a tensile modulus of 350 MPa, it is suitable for soft tissue engineering [23].

2.2. 3D Printing Parameters

Printing parameters included a nozzle temperature of 200 °C, a bed temperature of 50 °C, a voltage of 7.10 kV, and a bed speed of 150 mm/min, with a nozzle-collector distance of 3 mm and a nozzle diameter of 0.4 mm.

To output the designed geometries for the mesh implants, it was essential to generate a tailored G-code for the MEW device. This G-code defines the movement of the print head, regulates the filament extrusion rates, and outlines the layer deposition strategy. The auxetic meshes G-code was developed using FullControl software, allowing for customizable printing parameters [24].

In G-code, the E parameter is utilized to regulate the movement of the extruder in 3D printing (see Equation (1)). This value, represented in millimetres, corresponds to the amount of filament fed into the extruder and can be adjusted to accommodate different filament diameters. The calculation can be performed using Equation (1), where $D_{\mathrm{extrusion}}$ represents the desired fiber diameter in micrometres (µm). A conversion factor of $0.001$ is applied to transform measurements from micrometres to millimetres. The variable $L_{\mathrm{extrusion}}$ denotes the total length of the filament path as defined by the custom-generated G-code for each specific printed geometry, which can vary based on the geometric design and mesh dimensions. Moreover, the factor of $1.5$ serves as a calibration factor that has been empirically determined from preliminary experiments. The diameter of the PCL filament, referred to as $D_{\mathrm{market}\mathrm{filament}}$, is 1.75 mm.

$$E={\displaystyle \frac{{\left(D_{\mathrm{extrusion}}\times 0.001\times 1.5\right)}^2\times L_{\mathrm{extrusion}}}{{D_{\mathrm{market}\mathrm{filament}}}^2}}$$

(1)

All auxetic geometric designs utilized a consistent fiber diameter of 160 m throughout the fabrication process. This diameter was chosen based on previous studies and serves as a reference parameter for this research [7,25]. This study did not aim to conduct a parametric evaluation of fiber diameter but, rather, to assess the performance differences among various geometrically shaped designs.

2.3. Geometry Conception

Porosity is a crucial parameter in the design of auxetic mesh implants, significantly influencing both their mechanical stability and biological functionality. The mesh structure must be robust enough to prevent the collapse of small pores while maintaining geometric precision, an issue observed in synthetic meshes.

Below are descriptions of four auxetic designs used in this study:

1.

Lozenge grid, Figure 3a:

This configuration modifies the traditional hexagonal honeycomb by incorporating re-entrant (inward-buckling) cell walls. This design allows the structure to contract laterally under compression and to expand laterally when stretched. The angles of the re-entrant walls and the thickness can be adjusted to refine both the auxetic properties and mechanical performance of the material [26].

2.

Re-entrant Evans, Figure 3b:

The re-entrant honeycomb structure features unit cells with angles that protrude inward, forming an inverted or concave polygon shape. This arrangement enables the material to demonstrate a negative Poisson’s ratio, thus exhibiting auxetic behavior. The degree of auxeticity can be modified by altering the cell angles and the structure’s relative density [27,28,29].

3.

Three-star honeycomb, Figure 3c:

This configuration features unit cells shaped like three-pointed stars, with arms extending from a central point. When mechanical forces are applied, the arms of the stars flex and rotate, resulting in a negative Poisson’s ratio [30].

4.

Square grid, Figure 3d:

Lozenge grids consist of diamond-shaped units arranged in a grid pattern. When subjected to tensile or compressive forces, the lozenge shapes can rotate and deform in a manner that leads to auxetic behavior. The extent of this behavior is influenced by the geometry of the lozenges and their connectivity [30].

Figure 3. Auxetic designs: (a) lozenge grid geometry; (b) re-entrant Evans geometry; (c) three-star honeycomb geometry; (d) square grid geometry.

Figure 3. Auxetic designs: (a) lozenge grid geometry; (b) re-entrant Evans geometry; (c) three-star honeycomb geometry; (d) square grid geometry.

The cell unit dimensions of the auxetic meshes were designed to optimize mechanical performance and align with the biomechanical properties of vaginal tissue. Each geometry had distinct unit cell features affecting their stress distribution and mechanical behavior. As shown in Figure 4, each geometry exhibited distinct unit cell characteristics and dimensions.

2.4. Mechanical Testing

2.4.1. Auxetic Meshes

This research aimed to elucidate how various structural designs influence the mechanical properties of mesh implants, particularly in the context of their potential applications for POP repair. The mechanical behavior of biodegradable mesh implants produced through MEW was assessed via uniaxial tensile testing. Each experimental sample was designed using one of four specific auxetic geometries: the lozenge grid, re-entrant Evans, three-star honeycomb, and square grid geometries. These geometries were deliberately chosen based on their established negative Poisson’s ratio attributes, which considerably enhance their capacity to endure physiological loads while maintaining requisite flexibility.

A MECMESIN^® MultiTest 2.5-dV tensile testing machine was used, and to ensure stability during testing, the specimens were secured with mechanical wedge grips. Each sample was meticulously cut from the central region of the printed mesh, measuring 80 × 10 mm, to minimize potential edge effects that could result from variations in the geometry of the mesh perimeter. A total of three samples from each geometric design were tested to ensure consistent and reliable mechanical evaluation. Special attention was given to preserving critical structural elements and maintaining fiber continuity during the extraction of the samples.

All tests were conducted at a constant speed of 10 mm/min, with data recorded at a sampling rate of 10 Hz using a 100 N load cell. This setup captured measurements of force, displacement, and time.

Figure 5 presents the auxetic samples used in tensile testing.

2.4.2. Sow Tissue

The anatomical and cellular structure of the porcine vaginal region closely resembles that of humans, making it an effective model for investigating pelvic support and related disorders. Multiple studies have confirmed that the anatomical and histological characteristics of the porcine vaginal region are similar to those of humans, establishing pigs as a valuable model for researching pelvic support and associated disorders [31,32]. Sow tissue was also used in previous mechanical characterization studies to assess its performance [33,34].

Soft tissue samples from sows, as depicted in Figure 6, were sourced from a slaughterhouse (Euroabate—Matadouro Industrial, Lda, Marco de Canavezes, Portugal). Two female pigs (sows) were selected for this study, both approximately six months old and of comparable body weight. From each animal, three longitudinal tissue samples were taken from the mid-region of the vaginal wall, resulting in a total of six specimens for testing. The collection of multiple samples from each animal allowed for the evaluation and consideration of biological variability. For the uniaxial tensile testing of these soft tissues, longitudinal samples were collected and cut into rectangular specimens measuring 10 mm in width and 55 mm in length, with an average thickness of approximately 4 mm.

3. Results

Figure 7 illustrates the individual force–strain curves derived from the uniaxial tensile tests conducted on all samples, organized by each auxetic geometry (including re-entrant Evans, Lozenge grid, square grid, and three-star honeycomb). The bold curve represents the mean curve, calculated by averaging the force values at corresponding strain points.

Figure 8 provides a comparative overview of these averaged curves alongside the mechanical responses of vaginal tissue, a commercial synthetic mesh (Restorelle), and a conventional biodegradable square-shaped mesh from prior research. This comparison highlights the mechanical compatibility of the developed auxetic geometries in relation to both native tissue and existing implant solutions.

The re-entrant Evans geometry exhibited the highest load-bearing capacity, withstanding forces of approximately 7 N before significant deformation. This configuration demonstrated a negative Poisson’s ratio behavior, enabling lateral expansion under tensile loading. These characteristics make the Evans geometry particularly suitable for applications requiring enhanced structural stability and resistance to mechanical stress, such as POP repair.

The lozenge grid geometry exhibited an intermediate mechanical response, supporting loads of approximately 3.5 N. Its deformation behavior was similar to that of traditional square-shaped meshes. This design offers a balance between mechanical compliance and stiffness, making it a suitable transitional alternative for applications requiring moderate load adaptation while still benefiting from auxetic properties.

The square grid and three-star honeycomb geometries exhibited similar mechanical performance, demonstrating hyperelastic behavior and withstanding loads between 1 N and 1.5 N. Their lower stiffness indicates that they may be more suitable for applications where deformability is prioritized over load-bearing capacity, although they may offer limited stress distribution capabilities compared to the Evans and Lozenge designs.

4. Discussion

This study reveals valuable insights into the role of auxetic geometries in enhancing the mechanical performance of biodegradable melt electrowritten meshes designed for POP repair. The results show noteworthy variations in load-bearing capacity, stress distribution, and auxetic behavior among the different designs tested, reinforcing the promise of auxetic meshes as effective alternatives to traditional synthetic meshes.

Among the geometries investigated, the re-entrant Evans design stands out with the highest load-bearing capacity, enduring about 7 N before significant deformation occurs. However, its rigidity raises concerns: the mechanical properties diverge considerably from the vaginal tissue, suggesting that it may be too stiff for optimal performance in POP repair. This stiffness can partly be attributed to the manufacturing process, which causes material overlaps in certain areas, leading to increased thickness and resistance to deformation. As a result, while its strength is impressive, the re-entrant Evans configuration may not be ideal for cases requiring softer tissue compliance. Nevertheless, this does not warrant completely dismissing the design, as its inherent auxetic properties and impressive load-bearing capacity could prove beneficial if the printing process is optimized, as previously demonstrated in some studies [35]. Future efforts should concentrate on fine-tuning the G-code to minimize material over-deposition and to facilitate a mechanical response that more closely resembles vaginal tissue.

On the other hand, the Lozenge grid geometry, which supports around 3.5 N, showcases a more balanced mechanical profile, akin to traditional biodegradable square-shaped meshes [25]. Its auxetic properties offer a well-regulated response, making it a promising transitional option between high-strength designs and more flexible alternatives. This balanced behavior positions it well for moderate-load applications, where a mix of stability and adaptability is essential. Additionally, future studies could explore variations in the geometric angles to further refine its mechanical properties, optimizing its performance for pelvic organ prolapse repair [36].

The square grid and three-star honeycomb geometries reveal hyperelastic-like behaviors, supporting small loads. Compared to the lozenge grid, these structures exhibit 50–85% lower mechanical resistance than the re-entrant Evans design. Their force–strain curves closely mirror the mechanical response of vaginal tissue, positioning them as the most biomechanically compatible geometries in this study. Given that this work utilized a 160 $\mathrm{\mu }$m extrusion diameter, future investigations aim to explore larger fiber diameters to further align these geometries with the behavior of native vaginal tissue.

One of the standout features of auxetic scaffolds is their ability to mitigate the bundle effect—a common issue in conventional knitted and woven meshes. This issue often leads to uneven force distribution, creating localized stress concentrations, mechanical stiffening, and the potential for tissue erosion. The square grid and three-star honeycomb geometries excel at avoiding this problem. They distribute mechanical stress more evenly while maintaining compliance and adaptability. Their smooth stress transitions and auxetic expansion may further minimize the risk of localized tissue irritation, helping to reduce implant-related complications like inflammation and mesh contraction. Compared to commercial synthetic meshes, the PCL-based auxetic designs exhibit lower peak stress values. However, their ability to mimic the mechanical behavior of native vaginal tissue indicates better long-term compatibility. This is crucial in biomedical applications, where seamless integration with soft tissues helps prevent complications such as chronic pain, mesh contraction, or foreign-body reactions.

As we look ahead, the mechanical advantages showcased by the square grid and three-star honeycomb geometries provide a robust foundation for ongoing research focused on optimizing these designs. A primary objective will be to test larger extrusion diameters to further refine their stress-strain behavior, aligning more closely with the biomechanical properties of vaginal tissue. Additionally, enhancing the G-code files to reduce material overlap during the printing process will promote greater consistency in fiber diameter, thereby improving the overall mechanical reliability of fabricated meshes.

The findings from this study highlight that auxetic meshes offer significant biomechanical advantages compared to conventional POP repair materials, facilitating better tissue integration and lowering the risk of implant-related complications. By fine-tuning the manufacturing process and conducting biological validation studies, these advancements could lead to safer and more effective solutions in pelvic reconstructive surgery. The fabrication of full-scale, clinically relevant implants using MEW technology presents significant challenges due to the complexity of the processes involved. Addressing these challenges will be an objective of future research.

Biodegradable meshes offer advantages over permanent synthetic alternatives by reducing long-term issues such as chronic inflammation and reactions to foreign bodies. However, their use in clinical settings is limited by challenges related to mechanical support during degradation and managing inflammation from degradation byproducts. For PCL meshes, the goal is gradual degradation to promote tissue ingrowth, which replaces the mesh’s initial mechanical support. This process depends on factors like degradation rate, biological environment, and mesh design, and it requires thorough validation through preclinical and clinical studies. In vivo testing is essential for evaluating biocompatibility, degradation behavior, and long-term effectiveness.

Subsequent investigations will utilize sheep as animal models to explore the intricate biological interactions of these mesh materials within complex environments. Additionally, future studies will focus on the implementation of sandwich mesh structures that integrate both auxetic and reinforcing layers. This approach aims to enhance the mechanical performance, load distribution, and tissue integration of biodegradable implants designed for the repair of POP, as evidenced by findings from existing studies [37,38,39].

5. Conclusions

This study emphasizes the potential of MEW auxetic meshes as biomechanical alternatives for the repair of POP. These meshes offer enhanced stress distribution, reduced tissue damage, and improved adaptability compared to traditional synthetic meshes. Among the various geometries tested, the square grid and three-star honeycomb designs exhibited hyperelastic-like behavior, closely resembling the mechanical properties of vaginal tissue. In contrast, the re-entrant Evans geometry, despite its impressive load-bearing capacity, demonstrated excessive stiffness, rendering it less suitable for soft tissue applications. The unique ability of auxetic structures to counteract the bundle effect facilitates better mechanical integration and minimizes implant-related complications, thereby paving the way for safer and more effective biodegradable implants. Future research should concentrate on optimizing printing parameters, adjusting fiber diameters, and conducting in vivo studies to validate the long-term clinical applicability of these scaffolds, ultimately enhancing patient outcomes in the treatment of POP.