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. Author manuscript; available in PMC: 2025 Sep 26.
Published in final edited form as: Aesthet Surg J. 2025 Oct 16;45(11):1130–1140. doi: 10.1093/asj/sjaf100

Histomorphologic outcomes of GalaFLEX Scaffold used in breast surgery – clinical follow-up from 6 weeks to 63 months

Bruce W Van Natta 1,*, Catalina Pineda Molina 2,*, Vincent Antonelli 3, George S Hussey 4, Stephen F Badylak 5,&
PMCID: PMC12461751  NIHMSID: NIHMS2108028  PMID: 40614234

Abstract

Background:

The use of scaffolds in reconstructive and aesthetic breast surgeries for soft tissue reinforcement has increased over time. However, histomorphologic outcomes with the use of such materials are not typically reported. The present study describes the histologic findings associated with the use of the GalaFLEX™ Scaffold by BD (Lexington, MA), an absorbable biosynthetic material, when used as soft tissue support in breast surgery.

Objectives:

The present study evaluates the histomorphologic patterns of a 10-patient cohort that received GalaFLEX™ Scaffolds as soft tissue support in breast surgery, with and without breast implants.

Methods:

Tissue biopsy specimens that included the implanted GalaFLEX™ Scaffold were collected during revision from 6 weeks to 63 months post-implantation. General staining and specific immunolabeling were used to determine cellular infiltration, tissue composition and organization, and vascularization.

Results:

Biopsy specimens showed slow degradation of the GalaFLEX™ Scaffold, robust vascularization, mononuclear cell infiltration that decreased with time, and deposition of an organized collagenous connective tissue matrix in the interfiber space of the GalaFLEX™ Scaffold. There was no evidence for chronic inflammation or a foreign body response. The pattern of tissue remodeling around and within the fibers suggests a constructive tissue remodeling process rather than the formation of dense capsular tissue with contraction.

Conclusions:

Implantation of the GalaFLEX™ Scaffold for reconstructive and cosmetic breast surgery appears to be safe and is associated with slow scaffold degradation, neovascularization and mononuclear cell infiltration that diminishes with time, and a constructive remodeling response devoid of chronic inflammation or foreign body response. These conclusions are limited by the size of the 10-patient cohort.

1. Introduction

Reconstructive and aesthetic breast surgeries have significantly increased in popularity over the past two decades.1 These procedures encompass a range of interventions, including aesthetic surgeries such as breast augmentation, mastopexy, reduction, correction of congenital deformities, revision surgeries, and reconstruction following cancer treatment.

Breast augmentation remains one of the most common aesthetic surgical procedures for women, with 2.2 million procedures performed globally in 2023—a 29% increase since 2021. Overall, the number of breast-related procedures performed by plastic surgeons exceeded 4.1 million in 2023.2 In the United States alone, the American Society of Plastic Surgeons (ASPS) reported over 500,000 aesthetic breast procedures and more than 177,000 reconstructive surgeries in 2023.3

Breast reconstruction, which restores breast morphology following mastectomy or lumpectomy, has increasingly shifted toward implant-based techniques over flap-based methods.4 Although not yet FDA approved for breast reconstruction applications, the use of scaffolds in plastic and reconstructive breast surgeries has increased in recent years for a variety of reasons including the ability to address surgical challenges of ptosis, thin skin flaps, reduced skin elasticity, and fluctuation in weight that can complicate breast reconstruction, among others.5,6

Biologic, biosynthetic, and synthetic scaffolds in breast surgeries are frequently used to reinforce soft tissue and/or provide implant coverage in various clinical scenarios, including mastopexy (with or without implants), prevent implant rotation and malposition, and correct symmastia and asymmetry following reconstructions.7,8 Such scaffolds may enhance aesthetic outcomes by reshaping the implant pocket, offering improved support, and facilitating tissue integration.9 Additionally, scaffolds have been shown to reduce the risk of implant-related complications, such as capsular contracture, a common issue in breast reconstruction.10

Since its introduction in 2011, the GalaFLEX™ Scaffold by Becton Dickinson &Co. - BD (Lexington, MA) has emerged as an alternative to biologic and synthetic scaffolds derived from decellularized tissue extracellular matrices (ECM) or chemically derived polymers, respectively.7 GalaFLEX™ is an absorbable knitted monofilament scaffold composed of poly-4-hydroxybutyrate (P4HB),11,12 which degrades in the body to release its monomer 4HB, a molecule that is naturally present in mammalian tissue. Knitted P4HB meshes have previously shown to be effective in abdominal wall reconstruction and tendon repair.12–14 P4HB surgical meshes promote constructive tissue remodeling, reduce chronic inflammatory responses and fibrosis, and stimulate the secretion of antimicrobial peptides by macrophages.13–16 Clinical applications of the GalaFLEX™ Scaffold in breast applications have shown its ability to provide mechanical strength during the wound healing process which supports breast weight and maintains long-term tissue morphology, particularly when implanted in the lower pole of the breast.11

Previous studies have shown favorable outcomes with GalaFLEX™ Scaffold in a wide range of breast surgical procedures, including revision breast surgeries,5 immediate17 and two-staged18 prepectoral breast reconstruction, and direct-on-implant augmentative mastopexy.11,19 However, few publications have reported the histomorphologic tissue integration outcomes of GalaFLEX™ breast implantation.11,20 The present study evaluated the histopathologic characteristics and tissue integration patterns of GalaFLEX™ Scaffolds used as soft tissue support in breast tissue from a 10-patient cohort, with implantation times ranging from 6 weeks to 63 months.

1. Methods

The present study has been reviewed by Pearl IRB. An exemption was granted on the research project according to federal regulations: 45 CFR 46.104(d)(4) Secondary Research Uses of Data or Specimens 45 CFR 46.104(d)(4)(ii), 45 CFR 46.104(d)(4)(iii).

1.1. Surgical Procedures

The present study includes the histologic description of breast biopsy specimens from 10 patients that received a GalaFLEX™ Scaffold implant as part of their elective surgical plan. The primary surgical procedures included mastopexies, reductions, and implant augmentations as described in Table 1. Surgeries were performed between 2013 and 2016. All patients had informed consent for the primary procedure. The primary reason for revision in each patient was unrelated to the implanted scaffold. All primary surgical procedures and revisions were performed by a single plastic and reconstructive surgeon.

Table 1.

Patient histories of GalaFLEX™ explant specimens evaluated in this report.

Patient number Original Surgery Explant Timepoint Breast Implant? Reason for Revision Surgery
1 Dual plane augmentation with mastopexy 6 weeks Yes Persistent ptosis
2 Mastopexy 6 months No Recurrent ptosis
3 Mastopexy 7 months No Weight loss post bariatric
4 Reduction 9 months No Implant augmentation
5 Augmentation with inframammary skin excision 11 months Yes Persistent ptosis
6 Mastopexy 24 months No Macromastia
7 Augmentation 27 months Yes Correction of implant malposition
8 Reduction 30 months No Recurrent macromastia
9 Mastopexy 52 months No Scar revision
10 Reduction 63 months No Recurrent macromastia
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1.2. Specimen Collection

Tissue biopsy specimens were collected during revision surgeries performed between 2013 and 2020, ranging from 6 weeks to 63 months post-implantation. In all cases, samples were collected from waste tissue. From each patient, one to three samples containing the GalaFLEX™ Scaffold and surrounding breast tissue were harvested and placed in 10% neutral buffered formalin (NBF) followed by washes and preservation in 70%—95% ethanol.

1.3. Histomorphologic and Immunolabeling Methods

Fixed specimens were further processed at Alizée Pathology, LLC (Thurmont, MD). Each tissue sample was embedded in paraffin, sectioned and stained with Hematoxylin & Eosin (H&E) and Masson’s Trichrome (MT). Each sample was separately immunolabeled against CD-31 (Cat. No. PS5–16301, polyclonal rabbit) Invitrogen (Waltham, MA), smooth muscle actin (SMA) (Cat. No. BSB 5034, monoclonal mouse) BioSB (Goleta, CA), collagen type I (Cat No. ab138492, monoclonal rabbit) Abcam (Waltham, MA), and collagen type III (Cat. No. ab7778, polyclonal rabbit) Abcam (Waltham, MA). Briefly, each slide was deparaffinized with xylene and rehydrated with sequential washes in decreasing concentrations of ethanol. Following an antigen retrieval process, the slide was incubated with the primary antibody. Indirect detection of the antigen-antibody complex was performed with one of the following secondary antibodies: Rabbit-on-Farma HRP (Cat No. BRR4009) Biocare Medical (Houston, TX) or Mouse-on-Farma HRP (Cat No. BRR4002) Biocare Medical (Houston, TX), and visualized with DAB (Cat No. ACT500) ScTek Laboratories (Logan, UT). Finally, each slide was counterstained with hematoxylin. The presence and morphology of the P4HB fibers and the tissue response to the implanted GalaFLEX™ Scaffold was evaluated for cellular infiltration, tissue composition and organization, and vascularization. Two independent pathologists, one at Alizée Pathology and one at the McGowan Institute for Regenerative Medicine, provided a qualitative analysis of the samples.

2. Results

2.1. Patient’s Demographics

Samples from 10 female patients were included in this study. All patients were in good health at the time of primary and revision surgeries. The age of the patients at the time of the primary surgery ranged between 30 to 64 years old. The Body Mass Index (BMI) for 9 patients ranged within a healthy weight category, and one patient was categorized as overweight, based on the BMI metrics defined by the Centers for Disease Control and Prevention (CDC).21 All patients had previously had pregnancies, with 8 of these patients confirmed to have breastfed. A summary of demographic information from the patients is presented in Table 2.

Table 2.

Demographic data from patients

Patient number Age (years) Height Weight (pounds) Body Mass Index (BMI) BMI category* Parity Breastfed
1 33 5’5” 115 19.1 Healthy weight G2P2 Yes
2 35 5’8” 138 21.0 Healthy weight G3P4 Yes
3 50 5’0” 120 23.4 Healthy weight G2P2 Unknown
4 62 5’1” 103 19.5 Healthy weight G2P2 Yes
5 40 5’2” 128 23.4 Healthy weight G7P3 Yes
6 53 5’6” 135 21.8 Healthy weight G2P3 Yes
7 49 5’4” 120 20.6 Healthy weight G2P2 Yes
8 48 5’4” 120 20.6 Healthy weight G2P2 Yes
9 64 5’4” 165 28.3 Overweight G2P2 Yes
10 58 5’6” 145 23.4 Healthy weight G2P2 No
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*

CDC’s BMI categories: Underweight (BMI<18.5), healthy weight (BMI 18.5 to 24.9), overweight (BMI 25 to 39.9), obese (BMI ≥40).20

Gross inspection of the implanted GalaFLEX™ scaffolds at the time of revision surgery showed good tissue integration and good vascularization in all cases. None of the patients showed signs of infection or inflammation at the implant site. For all patients, revision surgeries included the removal of a section of tissue as part of the procedure, which contained GalaFLEX™ scaffold.

2.2. GalaFLEX™ Scaffold Material was Visible in Breast Tissue from all Samples Ranging From 6 Weeks to 63 Months Post-Implantation

All explanted specimens showed the presence of the P4HB fibers or residual P4HB material surrounded by various numbers of cells and vascularized extracellular matrix. These fibers did not stain positively with H&E (Figure 1). However, the fibers were visible as “grey” colored material in Masson’s Trichrome stained sections (Figure 2). The GalaFLEX™ Scaffold fibers were clearly identifiable within round to oval clear spaces early in the series, with the empty spaces becoming more irregular in shape and size at later time points, and the grey fibers becoming fragmented and less abundant. The fibers had well-defined surfaces, with acellular and homogeneous staining that varied with the duration of the implant.

Figure 1. Cellular response to GalaFLEX™ Scaffolds in the breast tissue.

Figure 1.

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Representative images of hematoxylin and eosin (H&E) stained cross sections at 6 weeks (A), 6 months (B), 7 months (C), 9 months (D), 11 months (E), 24 months (F), 27 months(G), 30 months (H), 52 months (I), and 63 months (J) after GalaFLEX™ Scaffold implantation in the breast. Scale bars 500 μm. Asterisks (*) identify the P4HB fiber or P4HB remnant material location within the tissue. Right bracket (]) indicate new tissue deposition in areas previously occupied by P4HB fibers. Arrows (→) identify the infiltration of mononuclear cells. Arrowheads (^) show the presence of multinucleate giant cells. Left braces ({) indicate an organized band of connective tissue immediately adjacent to the silicone implant location.

Figure 2. Tissue deposition around and within implanted GalaFLEX™ Scaffolds in the breast tissue.

Figure 2.

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Representative images of Masson’s Trichrome stained cross sections showing the patterns of collagenous fibrous tissue deposition at 6 weeks (A), 6 months (B), 7 months (C), 9 months (D), 11 months (E), 24 months (F), 27 months(G), 30 months (H), 52 months (I), and 63 months (J) after GalaFLEX™ Scaffold implantation in the breast. Scale bars 500 μm. Asterisks (*) identify the P4HB fiber or P4HB remnant material location within the tissue. Left braces ({) indicate an organized band of connective tissue immediately adjacent to the silicone implant location.

For all specimens at the earlier timepoints (6 weeks and 6–11 months) there was no appreciable degradation and no visible fragmentation of the fibers. As the length of time of implantation progressed (24–63 months), the integrity of the fibers diminished as evidenced by fragmentation of the material and more frequent “folding” that results from the microtome knife as the thin, 5–7 uM sections are created (Figure 1). In addition, the grey color intensity of the material diminishes with time. Moreover, the total area within the fiber spaces that was occupied by the P4HB material typically diminished compared to the area that was occupied by the material in the earlier time points. As shown in samples at 27, 30, 52 and 63 months, these areas were occupied with new extracellular matrix deposited around the fibers.

2.3. GalaFLEX™ Scaffolds Promote a Constructive Host Tissue Response

Evaluation of the specimens at all timepoints showed a non-adverse host tissue integration around and within the GalaFLEX™ Scaffold, with no signs of tissue encapsulation or foreign body response. The cellular infiltrate present in these samples was dominated by mononuclear cells that had morphology consistent with macrophages with lesser number of fibroblasts. The quantity of these cells within the tissue specimens diminished with time. The earliest specimen, at 6 weeks, showed the greatest number of mononuclear cells and these cells tended to be arranged in clusters. By the 6–11-month timepoints, the number and distribution of cells appeared to reach a steady state; that is, although cells undoubtedly continuously migrate into the scaffold, the number and distribution of these cells are not consistent with a typical inflammatory response but rather a healthy tissue remodeling process. Specifically, there was a virtual absence of polymorphonuclear cells and foci of necrosis and multinucleate giant cells, and there was a modest decrease in vascularization. The distribution of the mononuclear cells can be found both adjacent to and between the fibers of the GalaFLEX™ Scaffold. One of the more notable findings was the mononuclear cell distribution at later timepoints. Specifically, these cells were not concentrated adjacent to the GalaFLEX™ fibers as is typically seen with synthetic surgical meshes (Figure 1). Rather, these cells were present either individually or in small clusters in the interfiber space. In addition, there were rare multinucleate giant cells present in the earlier samples (6 weeks and 6 months) and such cells were virtually absent from the later time point specimens. The multinucleate giant cell is the sine qua non of the foreign body response; thus, this classic tissue response to biomaterials that reside for longer periods of time in the body does not apply herein.

The other cells that were present as part of the infiltrate and remodeling tissue include the endothelial cells that compose the vasculature and the fibroblasts that contribute to the collagen rich extracellular matrix. These cells are further described in the following sections.

2.4. GalaFLEX™ Scaffold does not promote capsular contraction in the human breast tissue

Collagenous connective tissue was present in and around all P4HB fibers within these specimens. This connective tissue filled the entire interfiber space and was associated with the presence of spindle shaped cells consistent with fibroblasts. Fibroblasts secrete the collagenous extracellular matrix.22,23 The confirmation that these specimens were dominated by collagen can be found in Masson’s Trichrome stained slides (Figure 2) and the immunolabelled slides for Collagen types I (Figure 3) and III (Figure 4).

Figure 3. Mature Collagen type I around and within implanted GalaFLEX™ Scaffolds in the breast tissue.

Figure 3.

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Representative images of immunostaining against collagen type I showing the patterns of mature collagenous fibrous tissue deposition at 6 weeks (A), 6 months (B), 7 months (C), 9 months (D), 11 months (E), 24 months (F), 27 months(G), 30 months (H), 52 months (I), and 63 months (J) after GalaFLEX™ Scaffold implantation in the breast. Scale bars 500 μm. Asterisks (*) identify the P4HB fiber or P4HB remnant material location within the tissue. Arrows (→) identify dark brown stain positive for collagen type I. Left braces ({) indicate an organized band of connective tissue immediately adjacent to the silicone implant location.

Figure 4. Deposition of Collagen type III around implanted GalaFLEX™ Scaffolds in the breast tissue.

Figure 4.

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Representative images of immunostaining against collagen type III showing the patterns of new collagenous tissue deposition at 6 weeks (A), 6 months (B), 7 months (C), 9 months (D), 11 months (E), 24 months (F), 27 months(G), 30 months (H), 52 months (I), and 63 months (J) after GalaFLEX™ Scaffold implantation in the breast. Scale bars 500 μm. Asterisks (*) identify the P4HB fiber or P4HB remnant material location within the tissue. Arrows (→) identify dark brown stain positive for collagen type III.

The deposition of the collagenous fibrous tissue occurred relatively early following implantation and appears as swarming bundles between the P4HB fibers. The earliest timepoint examined in this study was 6 weeks post implantation, at which time the collagenous connective tissue was less organized (more randomly oriented). The second earliest timepoint examined in this study was 6 months and the connective tissue was more dense and less randomly organized compared to the 6-week timepoint, often present in aligned bundles traversing the interfiber space. By the 11-month time point, there was evidence of progressive connective tissue remodeling, and the eventual consistent presence of organized collagenous connective tissue arranged in linear bands and swarming bundles surrounding the embedded P4HB fibers. This organized arrangement of fibers was present at all later time points that were represented in the cohort of patients (Figure 2).

It is worth noting that most samples showed randomly distributed small clusters of adipose connective tissue. These adipose clusters were more prominent at earlier time points compared to later timepoints. The adipose tissue clusters were randomly distributed throughout the thickness of the P4HB scaffold and interspersed within the fibrous connective tissue component.

It is clinically relevant that the spindle shaped fibroblasts present within the deposited collagen fibers did not stain positive for smooth muscle actin (SMA) (Figure 5), the molecular component most responsible for cell and associated tissue contraction. Stated differently, the deposited mature collagen seen in the P4HB specimens was not consistent with the histological presentation seen with the clinical phenomenon of “capsular contraction”10,24.

Figure 5. Smooth muscle actin (SMA) around implanted GalaFLEX™ Scaffolds in the breast tissue.

Figure 5.

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Representative images of immunostaining against smooth muscle actin showing the location of positive vascular myocytes and myofibroblasts at 6 weeks (A), 6 months (B), 7 months (C), 9 months (D), 11 months (E), 24 months (F), 27 months(G), 30 months (H), 52 months (I), and 63 months (J) after GalaFLEX™ Scaffold implantation in the breast. Scale bars 500 μm. Asterisks (*) identify the P4HB fiber or P4HB remnant material location within the tissue. Arrows (→) identify dark brown stain positive for SMA.

2.5. GalaFLEX™ Scaffolds support a vascularized remodeling response

The vascularity present within all specimens represented in this study was very robust, consisting of a mixture of capillary size vessels and arterioles. The identity of these structures as blood vessels was confirmed by immunolabeling with CD31 (a marker for endothelial cells) (Figure 6) and the presence of an adjacent layer of SMA-positive spindle cells (i.e., smooth muscle cells) (Figure 5) that form around arterioles and arteries. There was a modest decrease in the quantity of blood vessels in the specimens that represented longer implant duration, but even these specimens were well vascularized. As connective tissue assumes a more dense and mature phenotype, vascularity typically decreases. This pattern was observed in the present collection of specimens, although as stated above, the amount of vascularity was still robust even in the longer implant specimens. Vascularity was less within the scattered islands of adipose tissue which is consistent with the pattern of vascularity of normal adipose tissue.

Figure 6. Vascularization around implanted GalaFLEX™ Scaffolds in the breast tissue.

Figure 6.

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Representative images of immunostaining against DC-31 showing blood vessels around and within the GalaFLEX™ Scaffold at 6 weeks (A), 6 months (B), 7 months (C), 9 months (D), 11 months (E), 24 months (F), 27 months(G), 30 months (H), 52 months (I), and 63 months (J) after implantation in the breast. Scale bars 500 μm. Asterisks (*) identify the P4HB fiber or P4HB remnant material location within the tissue. Arrows (→) identify dark brown stain positive for DC-31.

2.6. Histomorphologic interactions of GalaFLEX™ Scaffolds and breast implants

Three of the evaluated specimens were from patients that had an augmentation procedure performed, with smooth, round, silicone gel implant (samples from revisions at 6 weeks, 11 and 27 months). The interface between the implant and the GalaFLEX device consisted of an organized band of collagenous connective tissue with a single layer of epithelioid cells occupying the surface of the fibrous tissue, i.e., immediately adjacent to the silicone implant (Figure 1A, 1E, 1G).

3. Discussion

The use of biologic, biosynthetic, and synthetic scaffolds in breast tissue reinforcement has become commonplace in plastic and reconstructive surgeries.5,11,25,26 Although not yet FDA-approved for breast augmentation or reconstructions, plastic surgeons often employ these scaffolds off-label, after thoroughly evaluating the associated risks and benefits with patients.18 These scaffolds provide structural support to the breast and help improve aesthetic outcomes.18 Among the commercially available scaffolds, those most commonly used in breast procedures include biologic scaffolds derived from human, porcine, or bovine dermal extracellular matrices, such as AlloDerm™,27 Strattice™,28 FlexHD®,29 and Fortiva®;6,9,10,30 absorbable biosynthetic scaffolds like GalaFLEX™31 Scaffold; and synthetic absorbable scaffolds, such as TIGR® Matrix,32 and DuraSorb®6,10,33 (Table 3).

Table 3.

Composition and properties of scaffold materials used in breast plastic and reconstructive surgery

Commercial Scaffold Name Composition Category In vivo Resorption Time Ref.
AlloDerm™ Human-Derived Acellular Dermal Matrix Biologic Scaffold 12 Months 27
Strattice™ Porcine-Derived Acellular Dermal Matrix Biologic Scaffold 12 Months 28
FlexHD® Human-Derived Acellular Dermal Matrix Biologic Scaffold 12 Months 29
Fortiva® Porcine-Derived Acellular Dermal Matrix Biologic Scaffold 12 Months 30
GalaFLEX™ Poly 4-hydroxybutyrate (P4HB) Biosynthetic Absorbable Monofilament 12–18 Months 31
TIGR® Fast Resorbing Copolymer: Glycolide, Lactide and Trimethylene Carbonate (TMC)

Slow Resorbing Copolymer: Lactide and Trimethylene Carbonate		 Synthetic Absorbable Multifilament 4 Months and 26 Months 32
DuraSorb® Poly dioxanone Synthetic Absorbable Monofilament 9 Months 33
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The specific characteristics of each scaffold, including material composition, three-dimensional structure, and absorption time influence the host immune response and the integration of surrounding breast tissue and associated connective tissues. Previous studies have shown that the GalaFLEX™ Scaffold provides structural support, long-term retention of breast position, and a reduced rate of capsular contracture when used for ptosis, whether in combination with breast implants or as a standalone soft tissue support.7,8,11,18 The present study evaluated clinical tissue samples for which GalaFLEX™ Scaffold was used as a soft tissue support, with and without breast implants, to assess histomorphological integration of the P4HB scaffold over time, from 6 weeks to 63 months, in a cohort of 10 patients that required revision surgery.

The host response to implanted scaffolds is a dynamic process, initiated by blood protein adsorption onto the biomaterial (known as the Vroman Effect), and continues until the scaffold is either fully resorbed and eliminated from the host tissue or embedded within the fibrous capsule of the foreign body response.34 Different phases in this process involve distinct cellular responses that play roles in determining the outcome.35,36 Following protein adsorption, an acute inflammatory cell response occurs, initially driven by neutrophils and later by mononuclear cells. This response generates a microenvironment that can either promote a constructive tissue remodeling or lead to chronic inflammation, encapsulation, and fibrosis.37,38 The activation and plasticity of immune cells, particularly macrophages, during the acute and subacute response (7–14 days post-implantation), influence the eventual outcome. A transition from pro-inflammatory M1-like macrophages to pro-remodeling M2-like macrophages is required to avoid a chronic inflammatory state.37,39,40

Histological analysis of the tissue biopsies from the present study showed a dynamic cellular response to the P4HB scaffold. The early timepoints showed the expected acute inflammatory response that progressively transitioned into an active tissue remodeling process. This tissue remodeling was characterized by a non-inflammatory cellular response, neovascularization and deposition of a swarming pattern of neomatrix. Over time, a steady state was reached, in which spindle cells and a low number of mononuclear cells comprised the microenvironment surrounding the remaining fiber architecture. This steady state with the presence of identifiable P4HB fiber substance persisted for at least 63 months.

The in vivo degradation of P4HB primarily occurs through bulk hydrolysis of the polymer with degradation product consisting of the 4-hydroxybutyrate monomer (4HB) or oligomer, a short-chain naturally occurring fatty acid that is found in various tissues of the body.12,16 Prior studies have shown that 4HB can activate molecular pathways in macrophages that promote the secretion of antimicrobial peptides, helping protect the tissue from bacterial infection.16,41 Ultimately, 4HB is metabolized through the Krebs cycle, with carbon dioxide (CO2) and water (H2O) as the final byproducts, without accumulating any harmful secondary metabolites.12 This degradation profile is consistent with previous reports on P4HB meshes in both animal models and clinical applications.20,42 As the P4HB mass decreases over time, the mechanical strength of the scaffold diminishes after approximately 12–18 months.42

Collagen deposition is an important aspect of tissue remodeling including applications involving the breast. Such collagen deposition occurs largely in response to mechanical forces.43,44 The organization and density of collagen observed in the tissue specimens followed Davis’s Law, which states that the amount and organization of connective tissue deposition is a direct and appropriate consequence of the applied forces.45 In the present cohort of patients, the applied forces consisted of the weight and pressure from adjacent tissues and associated implants. The collagen and extracellular matrix components that were deposited within and around the GalaFLEX™ Scaffold showed tissue integration, not encapsulation. Encapsulation would typically result in a band of connective tissue around the exterior of the entire scaffold, without extending into the interfiber spaces. The pattern of collagen deposition with vascularization observed over the course of 6 weeks to 63 months was consistent with a constructive tissue remodeling response.

Tissue vascularization is crucial for the homeostasis of the tissue, providing oxygen, nutrients, and defense mechanisms against infections.46 In the case of implanted scaffolds, a robust blood supply is even more critical as it supports cellular infiltration, new tissue deposition and protection against infection. As cells infiltrate the scaffold through the porous structure, they require an oxygen supply that is derived from diffusion of O2 from adjacent blood vessels.47 All examined tissue specimens, from 6 weeks to 63 months, exhibited a robust vascularization, indicating a supportive microenvironment within the scaffold. Since all biomedical implants are at risk for contamination/infection, the vascularity present in these samples provides assurance that the host immune system is fully available to minimize the risk of scaffold infection. A rich vascular supply is capable of supporting a constructive connective tissue remodeling response and necessary for sustained functionality.

There are limitations to the present study. Biopsy specimens were collected from 10 patients, a relatively small number without biologic replicates of the evaluated timepoints. Larger cohort studies, especially those including a diverse patient population, are warranted in future studies to validate the results of this study.

In conclusion, this study provides valuable insights into the histomorphologic characteristics of tissue integration and long-term degradation profile of the GalaFLEX™ Scaffold in breast tissue. The slow degradation of the scaffold, the patterns of tissue remodeling around and within the fibers, and the ability to support vascularization at the interfiber spaces demonstrate its potential as a safe and effective adjunct in breast plastic and reconstructive surgery.

Acknowledgements:

Alizée Pathology, LLC: Serge D. Rousselle, Molly Friedemann, James RL Stanley.

Funding Statement:

The University of Pittsburgh holds a Physician-Scientist Institutional Award from the Burroughs Wellcome Fund (V.P.A). Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number T32CA113263 (VPA).

Footnotes

Disclosure Statement:

B.V.N., C.P.M., G.S.H., and S.F.B. are consultants with Becton Dickinson and Co. (BD). B.V.N. is the Past President of The Aesthetic Foundation. V.P.A. declared no potential conflicts of interest.

Contributor Information

Bruce W. Van Natta, Associate Professor, Plastic Surgery Section, School of Medicine, Indiana University, Private Practice: Meridian Plastic Surgery Center.

Catalina Pineda Molina, Department of Surgery, School of Medicine, McGowan Institute for Regenerative Medicine, University of Pittsburgh.

Vincent Antonelli, Department of Surgery, School of Medicine, McGowan Institute for Regenerative Medicine, University of Pittsburgh.

George S. Hussey, Department of Pathology, School of Medicine, Department of Bioengineering, Swanson School of Engineering, McGowan Institute for Regenerative Medicine, University of Pittsburgh.

Stephen F. Badylak, Department of Surgery, School of Medicine, Department of Bioengineering, Swanson School of Engineering, McGowan Institute for Regenerative Medicine, University of Pittsburgh.

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