Postmastectomy radiotherapy causes capsular contracture due to fibroproliferation of the capsular tissue around the implant. In fibrosis, unlike normal wound healing, structural and functional disorders are observed in the tissues caused by excessive/irregular accumulation of extracellular matrix proteins. It has been reported that transforming growth factor-Ī²3 (TGF-Ī²3) prevents and reverses fibrosis in various tissues or provides scarless healing with its antifibrotic effect. Additionally, TGF-Ī²3 has been shown to reduce fibrosis in radiotherapy-induced fibrosis syndrome. However, no study in the literature investigates the effects of exogenously applied TGF-Ī²3 on capsular contracture in aesthetic or reconstructive breast implant application. TGF-Ī²3, which has a very short half-life, has low bioavailability with parenteral administration. Within the scope of this study, free TGF-Ī²3 was loaded into the nanoparticles to increase its low bioavailability and extend its duration of action by providing controlled release. The aim of this study is to investigate the preventive/improving effects of radiation induced capsular contracture using chitosan film formulations containing TGF-Ī²3 loaded poly(lactic-co-glycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG) nanoparticles in implant-based breast reconstruction. In the characterization studies of nanoparticles, the particle size and zeta potential of the TGF-Ī²3-loaded PLGA-b-PEG nanoparticle formulation selected to be used in the treatment group were found to be 123.60 Ā± 2.09 nm and ā34.87 Ā± 1.42 mV, respectively. The encapsulation efficiency of the formulation was calculated as 99.91 %. A controlled release profile was obtained in in vitro release studies. Chitosan film formulations containing free TGF-Ī²3 or TGF-Ī²3-loaded PLGA-b-PEG nanoparticles were used in in vivo studies. In animal studies, rats were randomly distributed into 6 groups (n = 8) as sham, implant, implant + radiotherapy, implant + radiotherapy + chitosan film containing unloaded nanoparticles, implant + radiotherapy + chitosan film containing free TGF-Ī²3, implant + radiotherapy + chitosan film containing TGF-Ī²3 loaded nanoparticle. In all study groups, a 2 cm incision was made along the posterior axillary line at the thoracic vertebral level in rats to reach the lateral edge of the latissimus dorsi. The fascial attachment to the chest wall was then bluntly dissected to create a pocket for the implants. In the treatment groups, the wound was closed after films were placed on the outer surface of the implants. After administering prophylactic antibiotics, rats were subjected to irradiation with 10 Gy photon beams targeted to each implant site. Each implant and the surrounding excised tissue were subjected to the necessary procedures for histological (capsule thickness, cell density), immunohistochemical, and biochemical (Ī±-SMA, vimentin, collagen type I and type III, TGF-Ī²1 and TGF-Ī²3: expression level/protein level) examinations. It was determined that the levels of TGF-Ī²1 and TGF-Ī²3 collagen type III, which decreased as a result of radiotherapy, were brought to the control level with free TGF-Ī²3 film and TGF-Ī²3 nanoparticle film formulations. Histological analyses, consistent with biochemical analyses, showed that thick collagen and fibrosis, which increased with radiotherapy, were brought to the control level with free TGF-Ī²3 film and TGF-Ī²3 nanoparticle film treatments.In biochemical analyses, the decrease in thick collagen was compatible with the decrease in the collagen type I/type III ratio in the free TGF-Ī²3 film and TGF-Ī²3 nanoparticle film groups. Changes in protein expression show that TGF-Ī²3 loaded nanoparticles are more successful than free TGF-Ī²3 in wound healing. In line with these results and the literature, it is thought that the balance of TGF-Ī²1 and TGF-Ī²3 should be maintained to ensure scarless wound healing with no capsule contracture.