Nanofat augmented fat grafting: a combined protocol for treatment of capsular contracture and actinic damage in patients undergoing implant-based breast reconstruction

Introduction In Italy and worldwide, breast reconstruction following mastectomy is most commonly approached with implant placement. A frequent and fearsome complication of this approach is capsular contracture, affecting severely 15-20% of women, causing shrinking of the implant and resulting in hindering pain, implant displacement and severe asymmetries. This complication can be as high as 40% in patients undergoing radiotherapy due to a synergistic effect between capsule formation and actinic-induced fibrosis. Current options to manage this complication include capsulotomy or capsulectomy with implant exchange, but this approach is burdened by a high percentage of relapse. Nonetheless, many patients are not willing to undergo a further major reconstructive procedure. Hence, more conservative but still effective approaches have been sought to improve this condition. In this scenario, regenerative medicine represents a valid option to improve tissue regeneration through adipose tissue transfer. Specifically, fat grafting presents both a filling action which improves breast irregularities and volume, and a regenerative action thanks to adipose derived stem cells (ADSCs) contained in the stromal vascular fraction (SVF) which, through in situ differentiation and production of growth and angiogenic factors, are able to improve actinic skin damage. At date, adipose tissue transfer to the breast is used to improve breast irregularities and volume and performed through the microfat injection technique, which involves liposuction from the abdomen or thighs of the patient, discard of non-fat cells and injection of adipose tissue to fill hollows. The problem with this technique is that a breast presenting capsular contracture and actinic fibrosis is stiff and not able to host large amount of tissue. This implies performing several procedures before reaching the desired result. A possible solution to this problem is the nanofat grafting technique, which consists in mechanical emulsification of the lipoaspirate obtaining a very fluid product which can be easily injected in stiff tissues, while maintaining the same adipose derived stem cells’ concentration. Currently nanofat grafting is applied effectively in facial rejuvenation and treatment of retracting scars, but is not extensively performed for treatment of implant-related complications. The aim of this study is to investigate whether a combined treatment with microfat and nanofat grafting is more effective than conventional microfat grafting alone in improving capsular contracture, breast actinic damage and patient pain. This might introduce a less invasive approach to a common problem in breast reconstruction, reducing the number of surgical procedures. Methods A prospective randomized case-control study was designed, setting as primary endpoint the assessment of improvement in skin actinic damage in the two groups using the LENT-SOMA scoring system. The assessment of capsular contracture in the two groups was made using Baker’s classification, while patient pain was assessed using a validated patient reported outcome measure which is the BREAST-Q. Candidates for the study are patients with previous implant-based breast reconstruction presenting severe capsular contracture and breast skin actinic damage. Patients presenting skin ulceration requiring implant removal, patients willing to undergo implant exchange or autologous breast reconstruction and patients with mild capsular contracture and actinic skin damage were excluded from the study. Preoperatively, demographic and perioperative data collection was performed together with patient evaluation which consisted in performing standardized preoperative photos, LENT-SOMA assessment of skin damage, Baker’s assessment of capsular contracture and preoperative administration of the BREAST-Q questionnaire. Patients were then randomly divided in a control group which received conventional microfat grafting and a study group receiving nanofat augmented fat grafting. The first postoperative evaluation happened six months postoperatively, when the injected adipose tissue was well integrated with the recipient site and had begun to exert its regenerative action. This evaluation follows the same criteria as the preoperative one. Homogeneity of the two groups was assessed to check for the presence of any confounding variables. Postoperative scores were compared between the two groups in order to assess whether one protocol was more effective than the other. Furthermore, pre and postoperative scores of each group will be compared to detect the improvement rate in each group. Power analysis was performed setting type I/II error at 0.05 and power to at least 80%. Results Fifty patients per group were recruited and the power of the study with this sample size was beyond 90%. Preoperative evaluation did not detect any statistically significant difference between the two groups when comparing the LENT-SOMA (p=0.977), Baker (p=0.233) and BREAST-Q scores (p=0.415). This demonstrates homogeneity between the two groups reducing the risk of bias in the postoperative evaluation. Postoperative evaluation showed a statistically significant improvement of skin actinic damage (p<0.001), pain and satisfaction with breasts (p=0.022) in patients receiving nanofat augmented microfat grafting compared to those receiving microfat grafting alone. Capsular contracture also showed better scores in the study group, but the difference was not statistically significant (p=0.055). Nanofat augmented fat grafting is a versatile and promising technique in treatment of capsular contracture and breast skin actinic damage after implant-based breast reconstruction and post-mastectomy radiotherapy. Considering the paucity of evidence in the present literature, more studies with a longer follow-up are needed in order to better assess these findings.