Long-term Outcomes of Poly-4-Hydroxybutyrate (P4HB) in Aesthetic Breast Surgery

Abstract

Background

Over the past decade, the use of poly-4-hydroxybutyrate (P4HB) in aesthetic breast surgery has grown in popularity. Published data on long-term outcomes, however, is scarce.

Objectives

The purpose of this study was to assess long-term outcomes with utilization of P4HB in various aesthetic breast procedures.

Methods

A retrospective review of all patients undergoing breast procedures with P4HB was performed by the senior author between July 2012 and March 2022. All patients with greater than 1 year of follow-up were evaluated, including demographics, surgical indications, complications, secondary procedures, and patient satisfaction. A Kruskal-Wallis test was performed to assess the stability of satisfaction over time.

Results

A total of 248 patients were evaluated. The mean follow-up length was 2.9 years (range, 1-9.3 years). The most common surgical indication was breast ptosis, which comprised 68% (n = 167) of patients. The overall complication rate was 8.0% (n = 20), with an unplanned reoperation rate of 2.8% (n = 7). Across the entire study population, the mean satisfaction score was 3.42 out of 4. When satisfaction scores were compared to follow-up length, Kruskal-Wallis test demonstrated no statistical differences (H = 18.2, P = .89, degrees of freedom [df]= 2), suggesting stability of satisfaction over time.

Conclusions

This study presents the senior author’s entire experience with P4HB across a wide range of aesthetic breast procedures. With an average follow-up length of almost 3 years, P4HB appears to be a both safe and effective tool to support soft tissue in aesthetic breast surgery. Further, high patient satisfaction appears stable.

Level of Evidence: 4

Poly-4-hydroxybutyrate (P4HB) is a component of human connective tissue and biomedically produced thermoplastic polyester.¹ After receiving initial United States Food and Drug Administration (FDA) clearance in 2007, an implantable monofilament P4HB scaffold was developed and FDA approved for soft tissue support in plastic and reconstructive surgery procedures in 2011 (GalaFLEX Scaffold; Becton, Dickinson, and Co., Franklin Lakes, NJ). When placed in breast tissue, P4HB is rapidly vascularized and subsequently resorbed over 12 to 18 months. The senior author (W.P.A.) was the 1st surgeon to use P4HB scaffold in aesthetic breast surgery in 2013.² Since then, multiple studies have reported on the safety and efficacy of P4HB in mastopexy and reduction mammaplasty up to 1 year postoperatively.^3,4 In these cases, the P4HB scaffold strengthens attenuated skin and breast tissue to stabilize breast shape and the nipple-areola complex.² Although the popularity of P4HB scaffold in aesthetic breast surgery has grown, long-term outcomes data beyond 1 year have not been formally investigated. The purpose of this study was to assess long-term outcomes with P4HB in various aesthetic breast procedures.

METHODS

A retrospective review of all patients undergoing breast procedures with P4HB performed by the senior author (W.P.A.) between July 2012 and March 2022. These dates encompass the senior author’s entire experience with P4HB, while allowing a minimum of 1 year of follow-up at the time of study execution (April 2023). Any patient whose surgery included P4HB scaffold was included. The only exclusion criteria was follow-up length of less than 1 year.

Data collected during chart review included age, surgical indication, specific surgical procedure, complications, length of follow-up, and secondary procedures performed (planned vs unplanned). During follow-up, patients were asked to rate their satisfaction with a 4-point Likert scale (1 = very dissatisfied; 2 = somewhat dissatisfied; 3 = somewhat satisfied; 4 = very satisfied). Patients were also asked about other breast procedures, both aesthetic and oncologic, they had potentially undergone elsewhere.

To evaluate the stability of patient satisfaction over time, patients were categorized by 3 groups based on length of follow-up (Group 1 = 1-2.5 years; Group 2 = 2.5-5 years; Group 3 = 5-9 years). A Kruskal-Wallis test was then performed to assess statistical significance between the 3 groups (P < .05). Statistical analysis was performed utilizing Excel (Microsoft Corp., Redmond, WA).

RESULTS

During the study period, a total of 345 patients underwent breast procedures with P4HB scaffold. Of this total cohort, 248 patients had documented follow-up of at least 1 year. The mean patient age was 38.2 years. The mean follow-up length was 2.9 years (range, 1-9.3 years). The most common surgical indication was breast ptosis, which comprised 68% (n = 167) of patients. Accordingly, mastopexy and augmentation-mastopexy were the most commonly performed procedures (35.5% and 33%, respectively). The remaining surgical indications and procedures are demonstrated in Tables 1 and 2.

The overall complication rate was 8.0% (n = 20), with an unplanned reoperation rate of 2.8% (n = 7). The most common complication was delayed wound healing, which occurred in 2.8% (n = 7) of patients. Four of these patients did have exposed P4HB scaffold, and were all successfully treated with excision of exposed scaffold and local wound care in the office. The only complication that could be directly attributed to P4HB occurred in 1 patient, who had palpable P4HB, requiring a return to the operating room for removal. The remaining complications can be found in Table 3.

Regarding secondary surgeries, the vast majority were planned as staged procedures. Twenty patients underwent staged augmentation after mastopexy, and 6 patients underwent staged mastopexy after augmentation. The revision rate for patients who underwent single-stage augmentation-mastopexy was 3.7% (n = 3/82), all of which were done to increase implant size. Regarding procedures done at outside practices, 1 patient underwent a lumpectomy for a benign lesion. There were no diagnoses of atypical hyperplasia or malignancy reported. No patients underwent procedures concerning breast findings at another medical facility.

Across the entire study population, the mean satisfaction score was 3.42 out of 4. The breakdown of patient satisfaction scores for the study population can be seen in Figure 1. The mean patient satisfaction scores by follow-up length (Figure 2) were 3.4 (Group 1), 3.4 (Group 2), and 3.5 (Group 3). Kruskal-Wallis test demonstrated no statistical differences (H = 18.2, P = .89, degrees of freedom [df] = 2) between the 3 groups, suggesting stability of satisfaction over time. Representative cases are demonstrated in Figures 3-5.

DISCUSSION

Plastic surgeons have long searched for an alloplastic material to support soft tissue during breast surgery. In the 1980s, Johnson described the use of permanent polypropylene mesh (Marlex; C.R. Bard, Inc., Murray Hill, NJ) during reduction mammoplasty, anchoring the lifted breast tissue to the second rib.⁵ Relying on a permanent product, this technique often caused long-term patient discomfort. Further, polypropylene mesh in mastopexy has been implicated in a report of chronic abscess formation.⁶

Góes further investigated the ability of alloplastic meshes and scaffolds to provide predictable long-term support in mastopexy.^7-11 His preferred mesh was a combination of permanent polyester and resorbable polyglactin fibers.¹⁰ More recently, 3-dimensional knitted permanent polyester mesh has been advocated, with a single-patient histologic study showing a thin layer of reactive collagen on the surface of the mesh; however, it is unclear if permanent polyester mesh strengthens the native tissue.^12,13

In 2017, W.P.A. published his initial experience with long-term resorbable P4HB scaffold to support the lower pole after mastopexy.² This product was chosen due to its unique properties: monofilament predictability, rapid rate of tissue ingrowth (95% integration in 7 days), 12- to 18-month resorption time, long-term strength (3-5x after resorption), and established history of human use.¹⁴ A subsequent multicenter study further demonstrated the ability of P4HB scaffold to support breast tissue in mastopexy and reduction mammoplasty up to 1 year postoperatively.³ Further, P4HB did not hinder mammographic or ultrasonographic breast surveillance. A more recent study by Mallucci expanded the published uses to include augmentation-mastopexy and correction of implant malposition.⁴ Although in this study only outcomes up to 1 year postoperatively were formally assessed, the mean follow-up time was 14 months with at least 1 patient followed for 3 years.⁴ Still, studies focusing on long-term outcomes in aesthetic breast surgery are lacking.

P4HB scaffold has also been utilized in breast reconstruction. In a study comparing acellular dermal matrix (ADM) to P4HB scaffold in subpectoral tissue expander–based breast reconstruction overall trends toward a decrease in infection rates, seroma rates, expansion times, and time until drain removal in patients treated with P4HB were found.¹⁵ Sigalove demonstrated the safety and cost effectiveness of a combined P4HB and acellular dermal matrix (ADM) construct in prepectoral breast reconstruction.¹⁶ Rehnke has described a novel prepectoral breast reconstruction technique that combines a 3-dimensional P4HB construct with autologous fat grafting.¹⁷ A recent publication described 2-stage prepectoral breast reconstruction with P4HB scaffold as a safe and effective technique with high patient satisfaction up to 2 years postoperatively.¹⁸

This study represents the largest experience with P4HB in aesthetic breast surgery. Further, it expands follow-up data beyond 1 year. In line with previous studies, the most common indication for surgery, and P4HB, was breast ptosis. Patients presenting for mastopexy and augmentation-mastopexy have, by definition, failure of the soft tissue suspensory system of the breast. In W.P.A.’s practice, all patients presenting with breast ptosis are offered P4HB scaffold. As previously published, patients with a vertical excess less than 6 cm are offered a simultaneous augmentation-mastopexy.¹⁹ Notably, in this cohort, the revision rate for single-stage augmentation-mastopexy was 3.7%, which is nearly identical to previously published data.²⁰

Consistent with Malucci's experience, P4HB is helpful in implant malposition corrections.⁴ In these cases, the pocket is revised with capsulorrhaphy, or a neosubpectoral pocket is created. P4HB is then utilized to bolster the repair or the neopocket against the weight of the implant. Additionally, P4HB can be helpful in preventing implant malposition in primary augmentation, which is important in patients with chest wall anomalies, including pectus carinatum, pectus excavatum, and sloping chest walls. Finally, P4HB improves implant pocket control and unique breast form stability after capsulectomy. P4HB appears to be protective against capsular contracture, likely through its unique gradation, antiinflammatory remodeling, and antimicrobial peptides it stimulates. There is an ongoing randomized controlled trial to formally investigate this.

Overall, the complication and revision rates in our cohort were favorable. The most common complication was delayed wound healing. If P4HB scaffold is placed in the subcutaneous plane, delayed wound healing, particularly at the T-junction of an inverted-T pattern, may result in exposed scaffold. Due to the intrinsic monofilament and antimicrobial properties of P4HB, exposed scaffold should be managed with local removal of the exposed scaffold and local wound care.²¹ In our experience, this has led to full healing without long-term complications in every patient.

Only 1 complication was directly attributable to P4HB. In this patient, an encapsulated piece remained palpable long-term, and therefore required excision. In this case, the scaffold was folded on itself, so that a central core of P4HB was not resorbed. To facilitate resorption, care must be taken that at least 1 side of the scaffold is placed against vascularized tissue. This is particularly important in revisional breast surgery—for example, if placed during capsulorrhaphy, discontinuous capsulotomies or partial capsulectomies should be performed adjacent to the P4HB to provide vascularity and properly integrate the scaffold.

P4HB is a scaffold, rather than a mesh, meaning it predictably resorbs, yet provides long-term added strength of the native tissue. Conversely, absorbable meshes provide no long-term strength. Additionally, P4HB exhibits a unique anti-inflammatory response during the tissue remodeling phase. In general, macrophages can be categorized by 2 subtypes, M1 and M2. M1 macrophages promote acute inflammation, cytotoxicity, and tumor suppression, whereas M2 macrophages promote resolution of inflammation, matrix deposition, and tissue remodeling.²² In vivo, macrophages exist on a spectrum between these 2 types, shifting their function based on the extracellular environment.²³ In response to a surgical mesh, a greater number of M2 macrophages and a higher ratio of M2:M1 macrophages are associated with more constructive tissue remodeling.²⁴ P4HB scaffold has been shown to produce a faster and more robust M2 response than polypropylene mesh, TIGR (Novus Scientific, Uppsala, Sweden), GORE BIO-A (Gore, Newark, DE), and acellular porcine dermis.²⁵

Due to this predominant M2 macrophage response, there has been an unsubstantiated and non-science-based concern regarding P4HB's oncologic safety. Macrophages that are found within a tumor microenvironment are termed tumor-associated macrophages (TAMs). TAMs can be either antitumorigenic or protooncogenic. Although some erroneously equate TAMs to M2 macrophages, this is an inaccurate description, because TAMs can share M1 and M2 signature polarization.²⁶ In a recent study, breast cancer TAMs have not shown a preferential enrichment for M2-associated genes.²⁷ Finally, TAMs display a unique set of cell surface molecules that are not equivalent to typical M1 or M2 cells.²⁸ Simply the presence, therefore, of a predominant M2 macrophage response does not equate to increased oncologic risk.

Clinically, we have not seen any oncologic issues in patients treated with P4HB. Although not formally assessed in this paper, no patients in our cohort reported malignant or premalignant lesions during the follow-up period. Similarly, findings have been reported in other reports in which no patients had a new breast cancer diagnosis or a recurrence of the cancer for which they originally underwent mastectomy.¹⁸ In a recent book chapter, Rehnke reported 3 local recurrences in females who had undergone breast reconstruction with 3-dimensional P4HB constructs.²⁹ Of note, all 3 patients received suboptimal oncologic treatment: the first patient did not receive trastuzumab for a Her2(+) tumor; the second patient's chemotherapy was aborted and hormonal treatment was stopped; and the third patient refused adjuvant chemotherapy and radiation treatment. Based on existing data, it appears that P4HB scaffold is safe for breast surgery. Future investigations, however, should continue to focus on oncologic safety.

Limitations of the study are those inherent to any review. First, without a control group, we cannot conclude that P4HB scaffold improved results, although that was not the emphasis and was already demonstrated in our previous publications.^2,3 The intended goal of this study was to investigate the long-term safety and efficacy of P4HB scaffold. Therefore a control comparison was not necessary. Second, patient satisfaction was not assessed with a validated patient-reported outcome measurement (PROM); however, there is no true validated scale for these types of specific procedures. Further, we have found that simple Likert analysis is easily conveyed by patients. Finally, although not a goal of this study, outcomes were not evaluated with standardized photography or quantitative measurements between defined breast landmarks.

CONCLUSIONS

Although the popularity of the poly-4-hydroxybutyrate scaffold in aesthetic breast surgery has grown, long-term data is still lacking. This study presents the senior author’s entire experience with P4HB across a wide range of aesthetic breast procedures. With an average follow-up length of almost 3 years, P4HB appears to be a both safe and effective tool to support soft tissue in aesthetic breast surgery. Further, high patient satisfaction appears stable up to 9 years postoperatively.

Disclosures

Dr Adams is a paid consultant for Becton Dickinson (BD; Franklin Lakes, NJ). Dr Adams is the corresponding author and the senior surgeon who performed all of the cases reviewed. BD was not actively involved in the study, and the research was not funded by BD. Dr Sinclair declared no potential conflicts of interest with respect to the research, authorship, and publication of this article.

Funding

The authors received no financial support for the research, authorship, and publication of this article.

REFERENCES

Author notes