Background/Objectives: As the incidence of breast cancer increases, reliable, effective, and innovative solutions are required for breast deformities following breast-conserving surgery. We aimed to evaluate the biocompatibility and efficacy of optimized three-dimensional (3D) micro-nanofiber scaffolds and demonstrate their clinical potential through preclinical experiments. Methods: Seven-week-old male Sprague-Dawley rats were randomized into four groups. Group I (control group) received a 2-dimensional (2D) micro-nanofiber scaffold weighing 0.2 g; Groups II–IV received 3D micro-nanofiber scaffolds weighing 0.2, 0.3, and 0.6 g, respectively. These were subcutaneously implanted into the dorsal region and harvested with the surrounding tissues at 4, 8, and 16 weeks for histological evaluation. Results: The number of inflammatory cells was higher in Group IV than in Groups II and III at 4 weeks, with a significant increase in Group IV (p < 0.01) compared with that in Group I. At 8 weeks, it was significantly increased in Group III compared with that in Group I. Furthermore, at 16 weeks, it was significantly reduced in Group IV (p < 0.05) compared with that in Group I. The fibrosis depth in the 3D scaffolds revealed significant differences in Groups II, III, and IV (p < 0.001) compared with Group I at 4 weeks. The collagen fiber densities in the 3D groups were higher than those in the 2D group at 8 and 16 weeks. There were no statistically significant differences between the 3D groups. Conclusions: Absorbable 3D micro-nanofiber scaffolds enhance tissue integration and extracellular matrix formation following post-mastectomy breast reconstruction.

Tissue engineering and regenerative medicine are shifting from passive tissue replacement toward instructive platforms that regulate cellular behavior, immune responses, vascularization, and extracellular matrix remodeling. This review examines recent advances in natural, synthetic, composite, and stimuli-responsive biomaterials, biofabrication and 3D bioprinting, stem and progenitor cell therapies, extracellular vesicles and other cell-free products, immunomodulatory scaffolds, skin organoids and organ-on-a-chip systems, nanotechnology, and artificial intelligence-assisted design. Particular emphasis is placed on plastic, reconstructive, and aesthetic applications, including skin and wound repair, craniofacial bone and cartilage regeneration, peripheral nerve reconstruction, vascularization, and dental and periodontal repair. The review also considers biomodulators and skinboosters as emerging regenerative-aesthetic interventions that aim to improve dermal hydration, fibroblast activity, collagen remodeling, and skin quality rather than provide volume replacement alone. Importantly, these technologies differ substantially in translational maturity, ranging from in vitro and preclinical platforms to early clinical interventions, established clinical products, and commercially available treatments for which durable regenerative efficacy remains incompletely validated. Throughout this review, biological plausibility and preclinical efficacy are therefore distinguished from human clinical evidence, regulatory or established clinical use, and commercial availability. Progress will require standardized characterization, mechanism-linked potency assays, clinically relevant models, and outcome measures that capture functional integration, durability, safety, and aesthetic performance.