Oncoplastic techniques aim to optimize cosmetic and oncologic results after BCS. Absorbable scaffolds may aid volume replacement while preserving radiotherapy (RT) planning and follow-up imaging, though clinical evidence remains limited. This interim analysis of a prospective, multicenter, single-arm trial (Tens-BBC/003/2021; NCT05941299) included 25 patients with 6 month follow-up after BCS and whole-breast RT. Outcomes were adverse events (AEs), device usability, pain (VAS), satisfaction, quality of life (BREAST-Q©), cosmetic and imaging results, and RT tolerance. Mean age was 53.6 years, BMI 24.8 kg/m2. Tumors were mainly in the upper-outer quadrant (52%); T1c in 56%, T1b in 20%, T2 in 24%. Histology was invasive ductal carcinoma in 72%, nodal status cN0 in 96%. Mean surgery time was 74.7 min; drains were used in 76%. REGENERA™ type A (70 mL) was implanted in 84%, type B (100 mL) in 16%. No major complications occurred. Of 94 AEs within 90 days, all were mild/moderate and unrelated to the device; four later AEs (in one patient) were possibly implant-related. Investigator satisfaction (VAS) improved from 8.4 at implantation to 9.2 at 6 months; usability targets were exceeded. Pain decreased from 2.3 to 1.56. BREAST-Q© showed higher breast satisfaction (+ 8.9, p = 0.041), reduced distress (–10.3, p = 0.006), and a modest decline in physical well-being (–11.6, p = 0.012). All patients completed RT; acute toxicity occurred in 44%, all grade 1–2. Cosmetic outcomes were good to excellent in 88%. Radiological integration was satisfactory, with no significant interference in MRI. REGENERA™ is safe, feasible, and biocompatible for volume replacement in BCS. It provides high satisfaction and favorable cosmetic results without compromising RT or follow-up imaging. Early results support its integration into oncoplastic practice, though long-term evaluation is required.