Protocol for single-arm clinical trial evaluating medical grade polycaprolactone breast scaffold implantation with autologous fat grafting for breast implant revision and congenital defect correction surgery

Abstract

Introduction

Revision surgery following primary breast augmentation is common due to well-reported long-term limitations of permanent silicone implants. There are limited options for revision breast augmentation which avoids using silicone implants. Scaffold-guided breast tissue engineering (SGBTE) is a novel technique which uses breast scaffolds additively manufactured from medical grade polycaprolactone (mPCL), which is implanted and filled with autologous fat graft. This approach avoids limitations as observed with permanent silicone breast implants as the scaffold is porous and biodegradable. This clinical trial evaluates the safety and efficacy of SGBTE.

Methods and analysis

This study is an open, single-arm, monocentric, interventional, prospective clinical trial. The trial is being conducted at the Royal Brisbane and Women’s Hospital (RBWH) in Herston (Queensland, Australia) of the Metro North Health Service. The trial investigates 15–20 women who require breast implant surgery and/or congenital breast defect correction surgery, where a mPCL breast scaffold is implanted and filled with autologous fat graft. The primary endpoint is postoperative device safety by assessing the rate of adverse device effect rate. Secondary endpoints include general adverse event frequency and severity, number of revision surgeries, general surgical outcomes and complications, patient-reported outcomes and volume replacement outcomes.

Ethics and dissemination

The RBWH Human Research Ethics Committee (EC00172) has approved this clinical trial (ethics approval: HREC/2021/QRBW/79906). Findings from this clinical trial will evaluate the safety and efficacy of implanting mPCL scaffolds filled with autologous fat graft. The results of this clinical trial will be published in a peer-reviewed journal and presented at scientific meetings.

Trial registration number

NCT05437757.

Correspondence to Professor Owen Ung; [email protected]

STRENGTHS AND LIMITATIONS OF THIS STUDY

• This study reports a clinical trial protocol for a novel surgical approach to breast implant revision surgery and/or congenital defect correction using scaffold-guided breast tissue engineering.

• This study comprehensively describes the recruitment strategy, surgical intervention and analysis for a clinical trial.

• This clinical trial protocol has been registered and approved by the Royal Brisbane and Women’s Hospital Human Research Ethics Committee, and the trial has commenced.

• This study is limited to establishing the safety and feasibility of implanting polycaprolactone breast scaffolds in breast revision surgery and/or congenital breast defect correction.

Introduction

Breast augmentation using silicone implants is one of the most common cosmetic surgical procedures, where 298 658 procedures were performed in 2022 in the USA.¹ However, revision rates following primary breast augmentation are common and are as high as 36%.² This is largely due to the well-reported complications from permanent prostheses such as capsular contracture and implant rupture, which essentially limits the lifespan of the implant.^{3 4} There is also an associated risk of developing rare breast implant-associated malignancies such as anaplastic large cell lymphoma⁵ and squamous cell carcinoma,⁶ as well as breast implant illness.⁷

Revision surgery usually involves removal of the implant with a capsulectomy and replacement with another silicone implant. However, some patients decline use of another silicone implant due to preference, and in this population, there are limited options for breast augmentation. One option is transferring autologous fat graft.⁸ However, its use is limited to small volume or contour corrections and usually requires repeat procedures due to variability in fat graft survival.⁹

Scaffold-guided breast tissue engineering (SGBTE) is a concept which uses additively manufactured scaffolds which are implanted to regenerate soft tissue and can be used as a method of breast augmentation in primary or revision surgery. These scaffolds can be designed and manufactured specific to the patient and are filled with autologous fat graft. Over time, the body acts as a bioreactor which supports tissue regeneration while the scaffold dissolves, resulting in a tissue-engineered construct of autologous tissue. Importantly, it avoids the use of permanent silicone implants and its associated issues as it is bioresorbable. The scaffold also offers mechanical protection of the transferred autologous fat graft, improving its survival and reliability.¹⁰ Ultimately, this SGBTE approach has the potential to improve the outcomes of breast revision surgery.

Robust preclinical data were the basis for the design of this trial. Our research group has been able to successfully apply SGBTE to regenerate soft tissue in multiple large animal studies^{11 12} as well as in a first-in-human case.¹³ The proposed trial is a feasibility safety assessment study of an absorbable medical grade polycaprolactone (mPCL) breast scaffold indicated for breast implant revision and/or congenital breast defect correction surgery.

Methods and analysis

Hypothesis

mPCL breast scaffold with autologous fat graft is a safe and effective method of soft tissue regeneration following breast implant revision or congenital defect correction surgery.

Objective

The objective of the clinical investigation is to demonstrate the safety and clinical performance of the mPCL breast scaffold in combination with autologous fat grafting for breast implant revision and congenital defect correction surgeries.

Study design and timeline

This study is an open, single-arm, monocentric, interventional, prospective clinical trial. The trial is being conducted at the Royal Brisbane and Women’s Hospital (RBWH) in Herston (Queensland (QLD), Australia) of the Metro North Health Service. The RBWH Human Research Ethics Committee (HREC) (EC00172) has approved this clinical trial (ethics approval: HREC/2021/QRBW/79906).

The clinical trial aims to recruit 15–20 patients. The study duration is 24 months per person. The clinical trial commenced in June 2022 and is ongoing with an expected completion date in December 2025.

Patient selection

Recruitment for this trial involved patients requiring breast implant revision by implant removal, capsulectomy and replacement, or patients with congenital defects who required reconstructive surgery with or without prior implants. Patients with a previous history of mastectomy or radiation were excluded. We have targeted this patient population because they already require revision breast surgery and have refused another silicone implant, where there is no established alternative. An unmet clinical need was addressed with this trial, maximising potential benefit for the patient and minimising the risk. In addition, it allows the safety and feasibility of implanting mPCL scaffolds to be primarily established in a population without a previous history of breast cancer surgery or ongoing treatment. The specific inclusion and exclusion criteria are listed in table 1.

Table 1

Inclusion/exclusion criteria for the clinical trial in scaffold-guided breast tissue engineering

Inclusion criteria

Females over the age of 18 requiring breast implant revision or congenital defect correction surgery, unilateral or bilateral. Patients willing and able to comply with the study requirements. Patients eligible to undergo MRI (ie, no implanted incompatible metal or metal devices, no history of severe claustrophobia). Patients capable of providing valid informed consent. Patients with sufficient body fat for homologous transplantation.

Exclusion criteria

Patients who have undergone radical mastectomy or radical removal of chest wall soft tissue. Patients who have had breast or chest wall irradiation. Patients with a prior history of infection in the breast region in the preceding 12 months. Patients diagnosed with or having a prior history of breast implant-associated anaplastic large cell lymphoma (BIA-ALCL). Patients having any condition or disease, including uncontrolled diabetes (eg, HbA1c >8%), that is clinically known to impact wound healing ability. Patients with a known history of immunodeficiency including HIV, concomitant systemic corticosteroid therapy, chemotherapy, synchronous haematological malignancy or other causes for secondary/primary immunodeficiency. Patients with known severe concurrent or intercurrent illness, including cardiovascular, respiratory, immunological illnesses, psychiatric disorders, alcohol or chemical dependence, or possible allergies that could compromise safety, compliance, or interfere with interpretation of study results. Patients with a body mass index (BMI) below 20 and above 30 (patients with a BMI above 30 may still be eligible pending assessment by the investigating team and documentation of rationale). Patients with a polycaprolactone (PCL) allergy. Women who are currently pregnant or breastfeeding, or who are planning to become pregnant within 2 years after the breast surgery. Patients who are ineligible to undergo MRI. Patients unable or unwilling to comply with the treatment protocol. Patients unwilling or unable to provide fully informed consent, including but not limited to patients with intellectual or mental impairment. Patients with a history of smoking (patients with a history of smoking may still be eligible pending assessment by the investigating team and documentation of rationale).

Consent

Before enrolment into the study and performing any screening activities related to the trial, each prospective participant will be given a full explanation of the study. Those individuals who are potentially eligible and wish to participate will be provided with the trial ‘Participant Information Sheet and Consent Form’ prior to participation approved by the RBWH HREC. During this procedure, the investigator informs the patient extensively about all aspects of the trial, including the provision of physical examples of mPCL breast scaffold. Potential participants will be given time to read through the information and ask any questions. The formal consent process will be undertaken by the treating surgeon and will be documented by the trial coordinator.

Recruitment strategy

Although the research team does not expect significant clinical complications based on previous animal and human studies, as an additional precaution, a risk management staged recruitment strategy is adopted. There is a checkpoint after the recruitment of the first patient to determine if any serious adverse event (SAE) or trial stopping criterion has occurred. If no criteria are met, then recruitment progresses, and another checkpoint is performed after the recruitment of the next four patients. This strategy is shown in figure 1.

Figure 1. Staged patient recruitment strategy adopted for the clinical trial in scaffold-guided breast tissue engineering. CA, competent authority; DSMC, Data Safety Monitoring Committee; HREC, Human Research Ethics Committee; SAE, serious adverse event.

Investigational device

The investigated device is legally manufactured by BellaSeno (HRB 32486) (Leipzig, Germany), which is a company specialising in the design and manufacturing of implantable class III (MDR - medical device reporting) medical devices made from mPCL. This device is manufactured by three-dimensional (3D) printing using mPCL which is filamentous, highly porous and absorbable. The volume of devices that will be implanted in this study will be limited to 200 cc and the maximum projection of the scaffold that will be implanted in this study will be limited to 4.9 cm. Selection of an appropriate breast shape and size of the device for an individual patient will be determined both by the investigating surgeon and patient based on the patient’s body shape, size and overall preference.

Each mPCL breast scaffold is pretreated with oxygen plasma to improve its hydrophilicity, and then gamma sterilised. It is enclosed in separate double-blister packaging, which includes the name of the product, the scaffold unique device identification (UDI), dimensions, instructions for safe use, expiry date, storage information and manufacturer information. A label will be affixed on each product box with large text stating that the products are for use in a clinical investigation only. In addition to the device, the implant card will be included, which details intended use, storage information, safety information, warnings and the manufacturer’s contact information.

Intervention

The procedure is performed in the operating theatres of the RBWH (QLD, Australia). Participants are placed under general anaesthesia, administered prophylactic perioperative antibiotics, positioned supine, prepped with antiseptic solution and draped. A suitable incision will be made that provides access, maintains contour and optimises blood supply and cosmesis. If the participant has a pre-existing implant, an implant removal and capsulectomy are performed. The capsule is sent for histological analysis. The breast pocket is washed with normal saline or an antiseptic solution. A surgical drain shall be placed in the pocket at the discretion of the surgeon. If a plane change is required, the pectoralis major muscle is sutured back onto the chest wall and a new prepectoral pocket is dissected to accommodate the breast scaffold. A change of sterile gloves is performed, the device packaging is opened and the mPCL breast scaffold is inspected for quality control checks, ensuring that the device is correct for the patient and sterility is maintained. The scaffold is then inserted through the inframammary fold (IMF) incision into the prepectoral pocket. The scaffold is filled with autologous fat graft harvested from the participant, aiming for the scaffold to be 50% filled according to volume, although this may be limited by the amount available to be harvested. The scaffold is filled by creating ribbons of fat graft in a fan-like projection and layered. The IMF wound is closed using 2-0 Vicryl (Ethicon, USA) or Monocryl (Ethicon) and 3-0 Monocryl (Ethicon) sutures in layers and dressed with sterile dressings.

Autologous fat graft is harvested from the participant’s abdominal region and/or thighs during the procedure. Small 2–3 mm stab incisions are made and the liposuction cannula is introduced. Tumescent solution containing 1 mg of epinephrine and 200 mg of ropivacaine in 1000 mL Hartmann’s solution is infiltrated in the harvest sites. Suction is then applied to the liposuction cannula and fat is harvested and collected in a sterile container. Once sufficient volume is harvested, the fat is washed in Hartmann’s solution to remove excess byproducts such as blood and tumescent fluid, then transferred into smaller syringes. A blunt large bore cannula is used to inject harvested fat graft into the scaffold. The harvest sites are sutured closed and dressed with a sterile dressing.

The participant is admitted overnight for postoperative observation and surgical wound review. It is expected that the participant is safe for discharge the following day after the procedure, but this is up to the discretion of the treating surgeon. Participants are assessed by the investigation team postoperatively at 1 week and 2, 6, 12 and 24 months.

Dependent on outcomes, there may be a need for a second fat grafting procedure. If less than 50% of the injected fat graft is retained on MRI, then this secondary procedure will be considered, depending on clinical safety and availability of donor sites. If a regrafting procedure is required, then core biopsy samples will also be taken for histological analysis to correlate clinical, radiographic and histological findings.

Table 2 outlines the schedule of study visits and actions required.

Table 2

Schedule of study visits for the clinical trial in scaffold-guided breast tissue engineering

	MDT review	Enrolment	Reconstruction surgery	1-week review	2-month review	6, 12 and 24-month reviews
Timepoint	−t2	−t1	t0	t1	t2	T3–5
Participant visit No	0	1	2	3	4	5–7
Time buffer	N/A	N/A	N/A	±3 days	±7 days	±7 days
Enrolment
Eligibility screen	X	X
Informed consent		X
Demographics		X
Medical history	X	X		X	X	X
Intervention
Reconstruction			X
Autologous fat graft			X
Assessments
Medical imaging
MRI		X			X	X
DCE-MRI						Optional
Ultrasound		X			X	X
Clinical assessment		X	X	X	X	X
Medication review		X		X	X	X
Adverse events review			X	X	X	X
Holger wound classification			X	X	X
Numerical pain rating		X	X	X	X
Assessment measures		X			X	X
BREAST-Q		X			X	X
Safety bloods and b-HCG		X		X	X	X
Clinical photography, 3D scan and/or 180° video		X		X	X	X

.BREAST-Q, BREAST Questionnaire; 3D, three dimensional; DCE-MRI, dynamic contrast-enhanced MRI; HCG, human chorionic gonadotrophin; MDT, multidisciplinary team.

Endpoints

The primary and secondary endpoints of this clinical trial are listed in table 3.

Table 3

Primary and secondary endpoints of the clinical trial in scaffold-guided breast tissue engineering

Outcome measure	Measure description	Time frame
Primary outcome measure
Postoperative device safety	Feasibility assessed through postoperative device safety measured through the adverse device effect (ADE) rate. ADE is defined as per EN ISO 14155:2020. This will be regularly monitored during inpatient and outpatient follow-up.	Assessed 12 and 24 months after surgery.
Secondary outcome measures
Adverse event rate and severity	Adverse events and severity are defined as per EN ISO 14155:2020. This will be regularly monitored during inpatient and outpatient follow-up.	Assessed daily during inpatient stay and as an outpatient at 1 week and 2, 6, 12 and 24 months after surgery.
Frequency of complications	Composite outcome of short-term and long-term complications. This will be regularly monitored during inpatient and outpatient follow-up.	Short-term complications will be assessed at 1 week and 2 months of follow-up visits. Long-term complications will be assessed at 6, 12 and 24 months of follow-up visits.
Number of revision surgeries due to adverse device effects	ADE is defined as per EN ISO 14155:2020. This will be regularly monitored during inpatient and outpatient follow-up with a study-specific questionnaire.	Assessed daily during inpatient stay and as an outpatient at 1 week and 2, 6, 12 and 24 months after surgery.
Feasibility assessed through frequency of successful breast surgeries	This will be assessed as a composite outcome of: Baseline and postreconstruction imaging data (MRI). Clinical images (photographs, 3D scan, 180° video). Objective baseline and postreconstruction measures measured using a tape measure: sternal notch to nipple (SN-N), breast base width (BBW), breast height, nipple to inframammary fold (IMF) (N-IMF).	The frequency of successful breast surgeries will be assessed at the 24-month visit. The outcome of the surgeries will be assessed at enrolment and at 1 week, and 2, 6, 12 and 24 months after surgery.
Feasibility assessed through patient-reported breast-specific outcomes	It will be measured using the BREAST-Q. Scales: Quality of life: Physical well-being: chest. Psychosocial well-being. Sexual well-being. Satisfaction: Breasts.	Assessed at 2, 6, 12 and 24 months after surgery.
Feasibility assessed through volume replacement	This will be assessed as a composite outcome of: Total breast, scaffold and fat volume within scaffold volume measured in cubic centimetres from MRI. SN-N, BBW, breast height and N-IMF measured in millimetres with tape measure.	Assessed at enrolment and at 2, 6, 12 and 24 months after surgery.

BREAST-Q, BREAST Questionnaire.

Analysis

Study population

All patients with at least one attempt to implant the mPCL breast scaffold device will be included in the safety population. The safety population will be the data set for the analysis of the primary study endpoint. Patients who were implanted with the mPCL breast scaffold device and additionally showing at least one measurement of a secondary endpoint will be included in the intention-to-treat population. Patients with no major protocol deviation and observed over the entire planned period constitute the per protocol population.

Surgical outcomes

Breast assessment measures will be compared at baseline and postoperatively. They include sternal notch to nipple, breast base width, breast height and nipple to IMF. General surgical outcomes such as wound healing, breast volume, laboratory results and complications will also be assessed. If an additional fat grafting procedure is required, histological analysis of a punch biopsy taken from the construct will be analysed to identify tissue type, vascularity and inflammatory reaction.

Imaging outcomes

Breast imaging will be compared at baseline and postoperatively. MRI and ultrasound will be performed to assess soft tissue volume retention and distribution. It will also be used to assess vascularity. Specialised imaging software, such as Materialise Mimics (Materialise NV), will be used to segment regions of interest for analysis. Clinical photography and 3D surface scanning will also be performed and analysed. The 3D scan is performed using an Artec Leo handheld device in a private consult room. The Artec Leo is a structured light scanner with a resolution of 0.1 mm, routinely used in clinical workflows to scan faces and bodies. The scans are processed using a validated manufacturer’s Artec Studio software to produce a digital 3D file and still images.¹⁴

Patient-reported outcomes

Pain assessment will be performed using a numerical rating scale, which is an 11-point scale ranging from ‘0’ representing no pain to ‘10’ representing worst imaginable pain. Quality of life and patient satisfaction will be assessed using the BREAST Questionnaire (BREAST-Q). The BREAST-Q module shall be used in this study assessing psychological well-being, sexual well-being, satisfaction with breasts and physical well-being with chest.

Data management

The collection of data will be performed according to Clinical Data Acquisition Standards Harmonisation. Data will be cleaned and deidentified. Data will be stored on a REDCap database, which is a secure web-based application. The application and data are stored on servers provided by Queensland Health and are managed in compliance with legislation applicable to the collection, management and storage of confidential health information, including the Hospital and Health Boards Act 2011 (QLD) and the Information Privacy Act 2009 (QLD), regulatory guidelines and policy regarding research. Paper-based source documents will be stored in compliance with Good Clinical Practice (GCP) and National Health and Medical Research Council (NHMRC) guidelines for a minimum of 15 years. Electronic data used for statistical analysis will be stored for a minimum of 15 years following completion of the trial. The statistical analysis will be conducted using R (R Core Team, 2024), version 4.3.0 or higher on a Windows 11 machine.

Protocol deviation

Protocol deviation is defined as failure to follow, intentionally or unintentionally, the requirements of the protocol. The investigator is not allowed to deviate from the protocol except with prior approval or under emergency circumstances. All deviations are to be documented and reported to the Sponsor. The Sponsor will review the report and determine if further actions are necessary, such as amending the protocol, reporting to the relevant authorities or terminating the trial.

Monitoring

All safety data will be reviewed by an independent Data Safety Monitoring Committee (DSMC) which will act as an expert, independent advisory capacity to monitor and protect participant safety. It will consist of three senior qualified surgeons with no financial or other conflicts of interest with the Sponsor or the investigators. The responsibility of the DSMC will be to review the research protocol, conduct annual reviews, conduct ad hoc safety meetings following an adverse event and make recommendations to the Sponsor concerning continuation, modification, suspension or termination of the study.

Discontinuation

Patients who are withdrawn from the study will not automatically have their mPCL breast scaffolds removed unless the device malfunctions or the device poses a significant risk to the patient. These devices can be removed electively, and patients may be offered a replacement intervention such as implanting another device or breast revision surgery (eg, mastopexy). In the circumstance that a device is removed, the device will be fixed in formalin and sent to the Sponsor. All patients will be asked to complete the remaining scheduled visits if possible.

Pregnancy

Patients are screened with a pregnancy test prior to enrolment in the trial and throughout the follow-up period. If the patient becomes pregnant during the study and the mPCL scaffold is already implanted, the scaffold will not be explanted unless there is a serious risk to the mother or child. Any planned autologous fat grafting procedures will be delayed until after the child is born. The patient will be observed according to the schedule of study visits. Based on the outcome of a risk assessment performed by the investigation team, an MRI may not be performed. The patient will also have an additional assessment at the end of the second trimester. If the mPCL breast scaffold is explanted, the patient will be asked to return for a final visit 4 weeks after explantation. During this visit, a safety assessment and a physical examination will be conducted. Details of the pregnancy and complications will also be documented.

Discontinuation due to unanticipated intraoperative findings

If intraoperative findings were to suggest the patient is unsuitable for mPCL breast scaffold implantation for any reason, the patient shall be excluded from the study. In such cases, mPCL breast scaffolds would not be implanted, and alternative conventional strategies used if consented prior to the procedure. If the patient underwent capsulectomy and the histological results of the capsule show any issue that can compromise the study outcome, the patient would be excluded from the study.

Discontinuation by the patient

The patient is entitled to terminate the clinical investigation at any time without giving any reason and without having to expect any hindrance from the investigator. If the patient requests an explantation and this is performed, then the date for study termination is the date of the explantation. The regular follow-up study visits should be completed if possible.

Lost to follow-up

If a patient does not attend an appointment and does not respond to three further attempts to contact the patient, they are considered as ‘lost to follow up’ and the attempts to contact the patient will be documented in the patient medical records. The date for study termination is the date of the last contact with the patient.

Termination by the investigator

The investigator can decide to terminate the clinical investigation for individual participants if there are concerns over patient safety, if there is an unexpected result which could compromise the study, if the patient meets an exclusion, or severe non-compliance by the patient towards the study.

Termination of the study

The study will be suspended if any SAE or serious adverse device effect (SADE) occurs related to the device or procedure which presents a significant safety issue (SSI), reconstruction failure due to the device deficiency, or if the patient cannot tolerate the mPCL breast scaffold. SSI is a safety issue that could adversely affect the safety of participants or materially impact on the continued ethical acceptability or conduct of the trial. In this circumstance, an ad hoc meeting of the DSMC, Sponsor and investigation team will be called to discuss and identify a solution to the issue. If the issue cannot be safely and reliably resolved, the clinical study will be terminated. The Sponsor will report to the relevant ethics committee and competent authority to provide an explanation for the suspension or termination.

Poststudy care

After study completion, all patients who were implanted with the mPCL breast scaffolds will be treated according to the hospital’s standard of care after breast reconstruction. Patients will be instructed to contact the site if there are any concerns regarding their procedure. In addition, the study patient will be instructed to continue to retain the patient information card providing information for future treating clinicians for the next 5 years.

Study participants of this feasibility study implanted with the polycaprolactone breast scaffold will be invited to participate in a planned post-trial long-term follow-up study after they reach their 24-month visit. Participants will be followed up annually, and visits will include activities such as physical examination, MRI (with contrast) and collection of any relevant clinical safety data, performed according to the standard of care (eg, mammography, if indicated).

Ethics and dissemination

Risk and benefit

The risk/benefit ratio of this trial is anticipated to be favourable. The trial investigates a population who already require a surgical procedure to revise their prior breast implants or require correction for a congenital breast defect. The protocol to insert mPCL breast scaffolds follows similar technical steps to inserting permanent breast implants for revision surgery.^{15 16} In addition, the protocol to harvest and inject autologous fat graft follows current standard clinical practice for breast augmentation or reconstruction.^{17 18} Therefore, the risk profile of this trial has similar inherent risks associated with the surgical procedures that the study population were going to undergo in lieu of this trial.

Specific risks of the procedure relate to the device. The scaffold is manufactured using only medical grade mPCL which is highly biocompatible and has a long history of safe clinical use in Food and Drug Administration-approved (USA) and CE-marked (Europe) implantable devices and sutures.¹⁹ CE marking is the medical device manufacturer’s claim that a product meets the General Safety and Performance Requirements (GSPR) of all relevant European Medical Device Regulations and is a legal requirement to place a device on the market in the European Union. Extensive preclinical studies and human trials have not resulted in any SAE or SADEs. There is minimal anticipated social harm to the patient other than inconvenience with study visits. There is minimal anticipated economic harm where incidental costs such as parking and transport will be subsidised as standard of care in Queensland Health for rural and regional patients referred from outside the Metro North Hospital and Health Service catchment.

The potential benefit of this trial is to establish a new method of autologous breast reconstruction that avoids complications associated with permanent breast prosthesis or transfer of large flaps. If successful, more patients may have access to a safer and more durable method of breast reconstruction, as well as benefit from the potential positive physical and psychological outcomes.

Sample size

As this is a feasibility study, a sample size of 15–20 patients is regarded as sufficient to evaluate the risk/benefit ratio for potential further studies. No comparison hypothesis will be tested; therefore, an adequate sample size to power comparative statistics will not be required.

Ethics and regulatory approval

The trial will be conducted in accordance with the principles of the Declaration of Helsinki, Notes for Guidance on GCP (CPMP/ICH/135/95), as adopted by the Australian Therapeutic Goods Administration (2000), with the NHMRC National Statement on Ethical Conduct in Research Involving Humans. The RBWH HREC (EC00172) has approved this clinical trial (ethics approval: HREC/2021/QRBW/79906).

Protocol amendments

Any modifications to the protocol which may impact on the conduct of the study, potential benefit of the patient, or may affect participant safety, including changes of study objectives, study design, participant population, sample sizes, study procedures or significant administrative aspects, will require a formal amendment to the protocol. Such amendments will be approved by the RBWH HREC prior to implementation.

Declaration of interests

It is recognised that the study represents a novel deviation from the current recognised standard of care provided to patients who need breast implant revision and congenital defect correction surgery. The mPCL breast scaffold used in this study will be provided free of charge by the Sponsor during the trial investigative phase. There is no financial involvement anticipated or apparent at the time of writing this protocol for all investigators involved which would lead to a conflict of interest.

Confidentiality

All patient information will be treated in strict confidence. Data which identify any study participant will not be revealed to anyone not directly involved in the research project or the clinical care of that participant. Patients provide written consent for their records to be accessed for the process of document verification or used for approved research projects. Participants are informed that their deidentified data will be transferred to a secure server for analysis, and results of the trial may be submitted to government agencies, presented at scientific conferences or published in scientific journals, but they will not be able to be specifically identified in such reports.

Dissemination policy

It is expected the results of this trial will provide early evidence for the effective role of SGBTE patients who would otherwise undergo breast implant reconstruction. The results will be published in a peer-reviewed journal with a focus on innovative surgical approaches. The work will also be presented at national and international conferences relevant to tissue engineering and plastic and reconstructive surgery. No results will be communicated to the participants.

Ethics statements

Patient consent for publication

Not applicable.

Footnote

Contributors Study conception and design: MC, GC, MW, OU. Acquisition of data: MC, GC, MW, OU. Data monitoring and analysis: MC, GC, MW, OU. Drafting of the manuscript: MC, GC, MW, OU. All authors read and approved the final version of this manuscript. OU is the guarantor.

Funding The primary sponsor for the trial is BellaSeno Pty Ltd (email: [email protected]).

Competing interests None declared.

Patient and public involvement Patients and/or the public were not involved in the design, or conduct, or reporting, or dissemination plans of this research.

Provenance and peer review Not commissioned; externally peer reviewed.

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