In the group treated with adipose-derived stromal cells preoperatively, eight patients (13.5 percent) underwent revision rhinoplasty after the operation. The reasons for revision surgery were infection (two patients), deviation (one patient), warping (two patients), and cosmetic dissatisfaction (three patients). The nasal infections were treated with antibiotics, including intraoperative antibiotics, irrigation, and postoperative antibiotic administration for 2 weeks. Patients with cosmetic dissatisfaction underwent revision surgery 6 months later without further complications. Two patients with warping refused to undergo further surgical correction. There were no other postoperative complications (Table 3).
In cases of severely deformed nasal tip or delayed wound healing at the nasal tip after surgery, additional adipose-derived stromal cell injections were applied. Nine patients (15.2 percent) received additional isolated adipose-derived stromal cell therapies 2 days after the operation (Figs. 6 and 7). They received on average 9.2 injections during a period of 15 days. Patients who received postoperative adipose-derived stromal cell injections had improvement in tip dimpling without any complications.
A 29-year-old patient exhibited skin discoloration, hardness, significant dimpling, and a cobblestone-like nasal envelope. Her surgical history included six prior rhinoplasties. She had her first surgery 10 years previously. During prior operations, silicone and Gore-Tex (W. L. Gore & Associates, Flagstaff, Ariz.) implants were used. Donor sites for prior grafts included septum, bilateral ear, and seventh rib cartilage. Six months before our treatment, she received Juvéderm (Allergan, Inc., Irvine, Calif.) filler injection from another clinic after nasal implants, and grafts were removed because of infection.
She received adipose-derived stromal cell therapy for 2 months (24 times) and showed improvement in skin discoloration and skin dimpling. After confirming the mobility of the nasal skin envelope, she underwent revision rhinoplasty. The rhinoplasty was performed using autologous ninth rib cartilage and dermal fat grafts. A composite scapha graft was also used to correct alar retraction. After rhinoplasty, she underwent additional adipose-derived stromal cell injections on the nasal tip for 2 weeks (Fig. 6).
A 25-year-old woman presented with tight immobile nasal skin and severely retracted columella. Her surgical history included five rhinoplasties. The first operation was performed 5 years previously. Two months previously, her silicone implant and cartilage grafts were removed because of infection. The patient underwent 40 days of isolated adipose-derived stromal cell treatment (26 times) to soften the nasal envelope. The patient then underwent revision rhinoplasty with autologous ninth rib cartilage for columellar strut grafting and dermal fat grafting for dorsal augmentation. The defect region at the soft triangle was treated with auricular composite grafting14 (Fig. 7).
A 22-year-old patient presented with a history of three rhinoplasties. The last operation was performed 2 months previously with a silicone implant and irradiated homologous costal cartilage. She then developed nasal infection, and 2 weeks before visiting our clinic, the implant and graft were removed. Severe infection and sustained inflammation collapsed the nostril and led to columella retraction. After 18 adipose-derived stromal cell treatments during a period of 30 days, the nasal envelope became soft and mobile. The autologous rib cartilage grafts from the seventh and ninth ribs were used for dorsal augmentation and columellar strut grafting, respectively. The patient was dissatisfied with the incomplete correction of the columellar retraction. Six months later, the retracted columella was further corrected with auricular grafting (Fig. 8).
The control group did not show any improvement in expansion of the nasal envelope or improvement of the nasal tip dimpling or mobility. One month after saline injections, all 21 patients underwent revision rhinoplasty with rib cartilage grafts. There was one case of nasal infection, which was treated with local antibiotic irrigations and oral antibiotics. One patient had warping of the dorsal bridge, which required revision surgery. Eight patients were dissatisfied with inadequate tip projection and overall aesthetic outcome (Fig. 9). None of these eight patients wished to undergo further corrective surgery.
There are two factors that need to be addressed in the correction of the severely contracted nose. One is expansion of the constricted nasal envelope, and the other is reestablishment of the desired stable internal framework. Expansion of the soft tissue in the contracted nose needs to be sufficient to allow for tension-free redraping during revision augmentation.
There are two ways to expand the nasal skin envelope. One is intraoperative expansion by means of wide dissection; the other is by softening the nasal envelope before surgery. First, in the mild or moderately contracted nose, intraoperative expansion by means of wide dissection of the nasal envelope from the surrounding cartilages, bone, and retaining ligaments is often sufficient to allow for tension-free redraping. However, in the severely contracted nose, the tight constricted nasal envelope does not expand adequately even with wide dissection. The limiting factor is the intrinsic thickening of the entire nasal envelope, including the skin. Even if the nasal envelope is maximally expanded intraoperatively, the tight nasal skin exerts pressure on the reconstructed internal framework, especially at the tip. Second, the vascular supply to the nasal envelope is tenuous from multiple surgical traumas and inflammation. Aggressive wide undermining may compromise the blood supply to the nose.
Our control group, which had saline injection to simulate the mass effect of tissue expansion before surgery, had insufficient skin envelope expansion. This is because patients with a severely contracted nose have hard scar tissue not only in the subcutaneous layer but also in the dermis. The mass effect of tissue expansion cannot restore the fibrotic dermis into healthy pliable dermis. We have also tried nonprocessed fat grafts in the past without any significant benefit.
We believe that the effectiveness of adipose-derived stromal cells is attributable to a high level of mesenchymal stem cells, which have regenerative properties.15–17 These properties have been noted in various clinical settings, including treatment of acute complications of nasal skin necrosis after filler injection.18 Adipose-derived stromal cells increased angiogenesis, which was visualized and assessed by CD31 and NG2 immunofluorescence stains and thermal infrared imaging.19–21 Therefore, adipose-derived stromal cells can be a therapeutic modality for ischemic conditions.22 In addition, adipose-derived stromal cell injection increased collagen synthesis and the number of fibroblasts in a mouse model.21 In chronic nonhealing wounds, such as Crohn fistulae, adipose-derived stromal cell treatment led to wound closure.23
We isolated adipose-derived stromal cells from harvested fat grafts through an enzymatic digestion and filtration process. By concentrating isolated adipose-derived stromal cells, we increased the number of adipose-derived stromal cells per amount injected. It is possible that growth factors were depleted during the process of adipose-derived stromal cell isolation. Although we did not directly compare fat grafting itself to adipose-derived stromal cell therapy, we found that adipose-derived stromal cell isolation effectively softened the hardened and contracted nasal envelope. Our method does not require cell culturing and is relatively simple to perform for use in a clinical setting.
By converting the hardened and contracted nasal envelope to a soft, mobile nasal envelope, we did not need to excise capsule or perform an extensively wide dissection. Excision of the capsule can lead to nasal envelope irregularity or excessive thinning of the nasal skin. Because these patients underwent multiple operations, the blood supply to the nasal skin was already tenuous. Avoiding extensive dissection and excision of the capsule minimizes circulation injury. Although all our patients presented to our clinic after the implant was removed, certainly adipose-derived stromal cells can be injected at the time of implant removal in the absence of infection.
In reestablishing the internal framework, tip projection, dorsal augmentation, and alar composite grafting were needed. For the tip projection, ninth rib cartilages were used in all our series as a columellar strut. Patients in our study already had septal and ear cartilage grafts. The rigid columellar strut served as a stable platform for the lower lateral cartilage to attach and remain at its desired position during the healing process. In addition, the extended tip position also tents the expanded dorsal skin and therefore helps maintain adequate space for the dorsal grafts. The dorsal graft is a carved rib cartilage graft or dermal fat graft depending on the dorsal height desired. A rib cartilage graft was used for moderate to significant dorsal projection, whereas a dermal fat graft was used for minimal augmentation. Although dermal fat grafts do not have firm or solid properties, the desired shape did not deform because of the minimal contractile force from the preexpanded soft nasal envelope. Other studies have used irradiated rib cartilages for internal framework,4 , 5 but we found that irradiated cartilage exhibits unpredictable resorptive properties. The use of various autologous grafts should be determined based on the surgeon’s preference or experience.
Nonsevere contracted ala can be solved with alar grafts.24 However, in severely retracted ala, skin expansion with isolated fat injection was inadequate. Therefore, composite skin cartilage grafts from scapha were needed in our series.
Patients with the most severely pinched and depressed tips required additional postoperative adipose-derived stromal cell injections for the nasal tip skin to soften. Certainly, we could have delayed revision surgery until the nasal tip healed sufficiently. However, patients with these deformities experience significant psychological difficulty and wish to undergo surgery as soon as possible. These patients often avoid social gatherings, and their nasal deformities negatively affect them in their work settings as well. We believe that as long as the nasal skin was expanded sufficiently to allow the internal framework to be established without being buckled by the tight nasal envelope, surgery could proceed. Postoperative adipose-derived stromal cell injection facilitated tip depression healing and was a viable postoperative treatment.
The degree of capsule softening versus dermal softening was not quantified, nor did we quantify the movement after each injection. The injection of adipose-derived stromal cells was in the plane between the capsule and the dermis. We did not see any fat grafts that we would normally see after fat grafting. We speculate that softening of both the capsule and the dermis contributed to softening of the overall softness of the nasal envelope. With each injection, there were improvements, but determining the amount of incremental improvement on the capsule and dermis would need further investigation on a standardized scar tissue model.
In our series, there were two cases of nasal infection. These two patients had significant postoperative swelling and seroma. The accumulated fluid was not drained and eventually led to infections that had to be treated with antibiotics for 1 month. Avoiding extensive wide dissection and meticulously applying external tape and compressive dressings to avoid dead space is important in avoiding seroma accumulation and potential postoperative infection.
Preoperative injection of isolated adipose-derived stromal cells into the contracted nasal scar tissue resulted in softening of the nasal envelope. Intraoperative release of remaining scar tissue and reconstruction of the internal framework with autologous grafts resulted in stable postoperative results. There were no recurrences of contracture and there were no ischemic injuries to the overlying skin.
Patients provided written consent for the use of their images.
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