Natural material scaffolds originate from biological tissues or their extracts, mainly including natural polymer polymers and decellularized matrices. Natural polymer polymers can be further divided into two subcategories: 1) Protein-based biomaterials: Common examples include collagen, gelatin, silk fibroin, fibronectin, and keratin. 2) Polysaccharide-based biomaterials: Mainly including hyaluronic acid, alginate, chitosan, cellulose, and chondroitin sulfate.

Collagen is the main structural protein in connective tissue. Due to its wide availability, low antigenicity, good biodegradability, and excellent biocompatibility, it is widely used as a tissue engineering scaffold. Some studies suggest that the occurrence of POP is related to damage to collagen structure and composition in tissues [11]. However, collagen itself has issues such as excessively rapid biodegradation, weak mechanical properties, and poor film-forming ability, thus its use alone for pelvic floor reconstruction is relatively limited. Chitosan [12] possesses good biocompatibility, promotes wound healing, and has antibacterial and bacteriostatic properties, helping to reduce the risk of infection and mesh exposure after implantation; however, its toughness is poor, making its mechanical support as a pelvic floor repair material insufficient. Decellularized extracellular matrix (dECM) scaffolds refer to extracellular matrix scaffolds obtained by removing cells from tissues or organs through decellularization techniques. They retain ultrastructure similar to native tissue, have low immunogenicity, and are rich in various growth factors, capable of transmitting physical, chemical, and biological signals, thereby promoting cell adhesion, proliferation, migration, differentiation, and angiogenesis, which is conducive to tissue regeneration [13]. Based on source, dECM can be classified into xenografts (e.g., porcine, bovine origin) and allografts (human origin). Xenogeneic dECM (e.g., porcine dermis, bovine pericardium) is widely sourced, lower in cost, and relatively common, but residual α-Gal antigens or DNA fragments may activate Toll-like receptor (TLR) pathways, inducing a Th1-type immune response, leading to chronic inflammation or graft contraction [14]-[16]. Zhu Keying etal. [17] found that allogeneic dECM has lower immunogenicity, and its ECM components are closer to recipient tissues, but its application is limited by donor scarcity and potential viral transmission risks. Other studies have shown that xenogeneic dECM implantation often induces M1 macrophage polarization, releasing pro-inflammatory factors like TNF-α and IL-6, whereas optimizing the decellularization process can promote M2 macrophage polarization, secreting factors like IL-10 and TGF-β, creating a microenvironment conducive to tissue repair [18][19]. Furthermore, research by Liu Xiu etal. [20] indicates that placenta-derived dECM contains immunomodulatory factors such as HLA-G, which can inhibit NK cell activity, thereby reducing rejection reactions.

Currently, synthetic materials dominate as scaffold materials for POP repair, mainly divided into non-degradable and degradable categories. Non-degradable materials are represented by PP; degradable materials include Polylactic Acid (PLA), Polyglycolic Acid (PGA), Poly lactic-co-glycolic acid (PLGA), Polycaprolactone (PCL), and Polyurethane (PU).

PP mesh possesses good thermal stability and excellent mechanical properties, with a slow degradation rate, making it suitable for long-term implantation applications. It is currently the most widely used POP repair material in clinical practice. However, its clinical application is associated with significant complication risks. Therriault etal. [21] showed that the complication rate after PP mesh implantation exceeds 10%. The core mechanism lies in the host’s immune response to the foreign material, mainly characterized by the dominance of M1 pro-inflammatory macrophages, forming a pro-inflammatory signaling microenvironment that affects tissue healing. A long-term implantation study in a sheep model demonstrated that PP mesh undergoes oxidative degradation over time invivo, manifesting as surface microcrack formation and oxidative product deposition. These changes may exacerbate local inflammatory reactions and increase the risk of mesh fracture [22]. Additionally, morphometric analysis of the vaginal mucosa suggests that PP material may have potential destructive effects on the local tissue microenvironment [23]. Despite issues such as late-stage erosion, exposure, and chronic pain associated with PP mesh, research on improving its prognosis through composite with other substances remains a current focus. Among degradable materials, PLA scaffolds can mimic natural fascial structure, possessing good cell infiltration, pro-angiogenic ability, and the capacity to induce M2 macrophage responses [24], helping maintain cell phenotype, promote metabolic activity, proliferation, and matrix and collagen deposition. However, PLA degrades slowly invivo, and the acidity of its degradation products (lactic acid) and the material’s high crystallinity can easily induce inflammatory reactions. PLGA exhibits good biocompatibility, controllable biodegradability, lower inflammatory response, and good film-forming properties. Its metabolites are non-toxic, have low immunogenicity, and it easily composites with other materials, but its mechanical strength is often limited. PCL is a semi-crystalline polyester characterized by good thermal stability, suitable mechanical properties, and a slow degradation rate. Its strength is comparable to native tissue, and it is easy to process and surface modify. Coimbra etal. [25] showed that surface-modified electrospun PCL patches possess good biomechanical properties and did not cause significant inflammatory reactions invivo; however, the PCL molecular chain lacks active groups like carboxyl, making the material surface relatively hydrophobic, which limits cell adhesion and proliferation to some extent.

PU serves as a physical carrier for pelvic floor implantation, maintaining its own strength and excellent elasticity, and can withstand certain pressure. PU can be customized according to the required elasticity and degradability. Shafaat etal.’s research confirmed that Z3 electrospun PU scaffolds with appropriate strength and elasticity have the potential to promote angiogenesis, showing application prospects for supporting pelvic floor structures [26]. Furthermore, Callewaert etal. [27] compared electrospun PU mesh and PP mesh in a sheep model, finding that both integrated well, with PU inducing a milder inflammatory response.

The pelvic floor repair environment is dynamic and complex, and single materials often struggle to fully meet its requirements. Consequently, researchers have developed composite material scaffolds by combining natural and synthetic materials, aiming to integrate the advantages of both: retaining the bioactivity of natural components (such as promoting cell proliferation and tissue regeneration) while achieving controllability in mechanical stability, degradation rate, and macroscopic structure from synthetic materials. The mechanism of action is primarily reflected in: the biological signals provided by natural components enhance cell adhesion and proliferation, while the synthetic skeleton ensures sufficient mechanical support during the initial stage of tissue regeneration; simultaneously, the composite strategy allows for fine control of the overall degradation rate by adjusting the component ratio, better matching the formation process of new tissue.

Wolf etal. [28] coated porcine dermis-derived extracellular matrix hydrogel onto the surface of polypropylene mesh. Invivo implantation in rats showed that compared to uncoated PP mesh, this hydrogel coating significantly alleviated foreign body reaction, oxidative stress, and cell apoptosis, indicating that modifying PP mesh through a composite strategy may enhance its clinical applicability for POP repair. Stangel-Wójcikiewicz etal. [29] conducted a comparative study in a sheep model, showing that chitosan material implantation induced a milder inflammatory response and resulted in better vaginal tissue healing compared to PP mesh implantation. However, the application of such composite materials still faces challenges in practice, such as sometimes low compatibility between materials, often requiring the addition of active components like cytokines to optimize function. Additionally, whether the degradation products of the material have adverse effects on surrounding tissues requires careful evaluation.

In recent years, 3D printing technology has brought new breakthroughs in the preparation of tissue engineering scaffolds. This technology allows precise control over the macroscopic structure and microscopic pores of scaffolds, enabling ordered distribution of seed cells in three-dimensional space. A review has systematically summarized the research progress on the application of 3D bioprinting in the pelvic floor field [30]. Paul etal. [31] utilized 3D bioprinting technology, using melt electrospun fibers as a supporting framework and printing endometrial mesenchymal stem cells (eMSCs) encapsulated in an aloe-alginate hydrogel. The results showed that compared to 3D printed mesh alone, this cellularized scaffold significantly reduced foreign body reaction and degradation-related adverse responses, recruited more host macrophages, and promoted scaffold-host tissue integration. Wu etal. [32] used a composite material of PCL and silk fibroin as bioink to prepare composite mesh via 3D printing that exhibited excellent mechanical properties, good biocompatibility, controllable degradation, and the ability to promote ligament and muscle fiber repair. Chen etal. [33] combined solution-extrusion 3D printing with coaxial electrospinning technology to develop a biodegradable pelvic floor prolapse repair pad. This repair pad utilized a PCL mesh as a scaffold, surface-coated with a PLGA nanofiber layer loaded with multiple active ingredients (lidocaine, estradiol, metronidazole, and connective tissue growth factor), structurally mimicking the characteristics of the natural connective tissue extracellular matrix. Recent studies further indicate [34] that combining computational modeling with 3D printing for degradable meshes holds promise for achieving personalized and safer surgical treatment of POP.