Plastic and reconstructive surgery relies heavily on implant-based devices, particularly implants used in breast augmentation, craniofacial repair, and soft-tissue reconstruction, making them among the most common procedures in this field worldwide. Among these, silicone implants (commonly polydimethylsiloxane, PDMS-based) are the most widely used, with polyurethane-coated implants and other variants also applied in clinical practice. A natural consequence surrounding implants is the formation of a fibrous capsule, which is essentially a foreign body reaction (FBR). However, this often leads to unexpected complications such as capsular contracture [1], [2], bacterial biofilm infections [3], increased risk of implant rupture [2], [4]. These complications compromise long-term implant stability and functionality. Patients are typically required to undergo implant replacement within 10–20 years due to these complications [5]. Therefore, exploring effective strategies to mitigate peri-implant capsule formation in plastic surgery has become a critical issue that needs to be urgently addressed.

The formation of a fibrous capsule involves six stages: (i) blood-biomaterial interaction, (ii) provisional matrix formation, (iii) acute inflammation, (iv) chronic inflammation, (v) foreign body giant cell (FBGCs) formation, (vi) fibrous capsule formation. Following implantation, the initial event is the blood-biomaterial interaction, where plasma proteins (primarily albumin and fibrinogen) adsorb onto the material surface. Depending on the surface properties of the material, these proteins undergo conformational changes, triggering a protein recognition pattern that recruits innate immune cells—neutrophils, monocytes, macrophages, and polymorphonuclear leukocytes (PMNs)—forming a provisional matrix. During the acute inflammatory phase, neutrophils serve as the first responders, arriving at the implantation site within 2 days [6]. PMNs play a crucial role in this process by migrating from blood vessels and infiltrating the implant site. These PMNs secrete cysteinyl leukotrienes (CysLTs)—a class of potent pro-inflammatory lipid mediators—which regulate their own recruitment and survival via autocrine and paracrine signaling pathways. Additionally, CysLTs stimulate fibroblast migration and proliferation during subsequent chronic inflammation [7]. The acute phase typically lasts about one week before subsiding spontaneously. However, if a foreign body persists, the acute inflammation transitions into chronic inflammation [8]. This stage, lasting approximately 3 weeks, is characterized by monocyte infiltration and macrophage activation [9]. Activated macrophages can polarize into M1 (pro-inflammatory) and M2 (anti-inflammatory/tissue-remodeling) subtypes. M1 macrophages secrete pro-inflammatory cytokines, including interleukin-1 (IL-1), and chemokines [10], while M2 macrophages upregulate anti-inflammatory pathways, secrete transforming growth TGF-β and tissue repair. Initially, M1 macrophages dominate the immune response to tissue injury. As chronic inflammation resolves, macrophage polarization shifts toward M2 phenotypes, promoting natural wound healing. However, the presence of an implant delays this transition, sustaining pro-inflammatory macrophage proliferation. Macrophages attempt to eliminate the implant via phagocytosis, releasing reactive oxygen species (ROS) and matrix metalloproteinases (MMPs) [11]. For slowly degradable or non-degradable implants, persistent macrophage frustration leads to their fusion into FBGCs [12]. Antigen-presenting pro-inflammatory macrophages also activate adaptive immune cells. Among them, ILCs, γδ+ T cells, and CD4 + T cells secrete IL-17 to promote fibrosis, with the interplay between IL-17 and senescent cells further exacerbating fibrotic progression [13]. In addition, different T-cell subsets (Th1, Th2, Th17, Treg, γδT, and CD8 + T cells) orchestrate both pro-fibrotic and anti-fibrotic responses in peri-implant tissues [14]. When the extracellular matrix (ECM) is compliant or adhesion to the material surface is insufficient, cells mainly form immature focal adhesions that are unstable under low tension [15]. To stabilize adhesion, fibroblasts enhance contractility via the Rho/ROCK signaling pathway [16]. In parallel, factor-beta (TGF-β) released from activated macrophages and fibroblasts synergistically activates both Smad-dependent and Smad-independent (including Rho/ROCK) pathways [17]. These signals drive fibroblast differentiation into myofibroblasts, which are characterized by the expression of α-smooth muscle actin (α-SMA) in cytoplasmic stress fibers and the secretion of collagen (primarily type III) [18]. Ultimately, these processes generate a dense, avascular collagenous network—the fibrous capsule—encasing the implant. In prolonged immune responses, the capsule thickens, with type I collagen becoming predominant [19]. Fibrosis is a complex process involving multiple molecular events, including enzymatic regulation. The primary enzymes responsible for ECM degradation are MMPs [20], which are counterbalanced by tissue inhibitors of metalloproteinases (TIMPs) [21]. The MMP/TIMP equilibrium ultimately dictates collagen deposition and ECM composition.

Current strategies to mitigate capsular fibrosis in plastic surgery implants primarily fall into two categories: (i) targeting upstream nonspecific protein adsorption (i.e., fouling) (ii) intervening in downstream inflammatory events [22]. Common anti-fouling approaches include surface modification techniques and ECM coatings, while anti-inflammatory strategies encompass drug-eluting coatings and bioactive factor delivery. However, many interventions simultaneously address both mechanisms, making strict classification impractical. Substantial evidence implicates bacterial biofilm formation as a critical contributor to capsular fibrosis and even capsular contracture [23], [24], [25]. Consequently, antibacterial technologies are frequently employed as adjuvant preventive measures. Additionally, intraoperative optimizations and postoperative adjunct therapies play indispensable roles. This review systematically consolidates current intervention strategies for reducing peri-implant capsular formation in plastic surgery, focusing on four key approaches: material surface modification techniques, pharmacological interventions, bioactive therapies, as well as intraoperative optimizations and postoperative adjuvant treatments (Graphical abstract), while also outlining potential future research directions in this field.