Regenerative High Purity Type I Collagen Scaffold for Breast Cancer Excision Repair and Reconstruction: A Prospective Multicenter Clinical Trial
Phase: NA
Conditions: Breast-Conserving Surgery
Sponsor: Adichunchanagiri Institute of Medical Sciences, B G Nagara

Title: Regenerative Collagen Scaffold for Breast Volume Restoration in Breast-
Conserving Surgery 
 
NCT No: NCT07219316 
 
Date: March 04, 2026 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

INTRODUCTION 
Breast-conserving surgery (BCS) has become the standard surgical approach for early-stage 
breast cancer, offering oncologic outcomes equivalent to mastectomy while preserving the 
native breast mound. Despite its advantages, excision of tumor-bearing tissue frequently 
results in postoperative volume deficits, contour deformities, and asymmetry, which can 
significantly compromise cosmetic outcomes and patient quality of life. These deformities are 
particularly impactful in small- to moderate-volume breasts, where even modest tissue loss 
may produce visible distortion [1]. 
Traditional strategies for managing post-BCS volume loss include volume displacement 
techniques, regional or local flaps, autologous fat grafting, and, less commonly, implant-
based approaches. While effective in selected cases, these methods are associated with 
important limitations. Flap-based reconstruction increases operative complexity and donor-
site morbidity, fat grafting is limited by unpredictable resorption and the need for repeat 
procedures, and implants are generally unsuitable for partial defects and may interfere with 
radiotherapy and oncologic surveillance [2]. Consequently, there remains an unmet clinical 
need for minimally invasive, biologically compatible solutions capable of restoring volume 
while preserving breast architecture and oncologic safety. 
The ideal volume restoration strategy following breast cancer resection in BCS would 
combine several key features: (1) immediate structural support to prevent cavity collapse, (2) 
biological integration promoting neovascularization and tissue regeneration, (3) minimal 
additional surgical morbidity, (4) compatibility with adjuvant radiotherapy, (5) preservation 
of imaging interpretability for cancer surveillance, and (6) predictable, durable cosmetic 
outcomes. Currently, no single technique fulfills all these criteria, highlighting a critical gap 
in oncoplastic breast surgery that regenerative biomaterials may address. 
Regenerative medicine approaches have gained increasing attention as alternatives to 
traditional reconstruction. Among these, collagen-based scaffolds have emerged as promising 
tools due to their ability to provide immediate structural support while simultaneously 
promoting host tissue integration, neovascularization, and gradual remodeling. Type I 
collagen, the principal structural protein of the extracellular matrix, plays a central role in 
wound healing and tissue regeneration by supporting fibroblast migration, angiogenesis, and 
organized tissue deposition [3, 4]. 

An evolution in collagen biomaterials, un-crosslinked High-purity Type I collagen (HPTC) 
with added bioactivity through phosphorylation is characterized by reduced antigenicity, and 
predictable biodegradation and reliable tissue integration. Extensive clinical experience with 
HPTC-based constructs in complex wound environments has demonstrated their capacity to 
facilitate durable tissue regeneration across a range of indications. Early work describing 
novel collagen application techniques over meshed split-thickness skin grafts highlighted 
improved graft stability and wound coverage in challenging defects, establishing the 
biological versatility of collagen scaffolds in surgical reconstruction [1]. Subsequent clinical 
series demonstrated the successful use of collagen-based matrices as alternatives to flap 
coverage for exposed bone and tendon, further supporting their load-bearing and regenerative 
capabilities [2]. 
Randomized controlled trials conducted by our group and others have consistently shown 
superior or comparable outcomes with HPTC-based skin substitutes compared with 
dehydrated human amnion/chorion membrane (dHACM) in diabetic foot ulcers, venous leg 
ulcers, and pressure ulcers, with advantages in healing rate, tissue quality, and safety profile 
[3-7]. These findings have been reinforced by multicenter trials and systematic reviews 
demonstrating favorable histopathological remodeling, angiogenesis, and epithelialization 
with HPTC use in chronic wounds [8]. Beyond wound care, collagen-based biomaterials have 
also shown efficacy in complex surgical scenarios, including the management of infected 
prosthetic meshes, where collagen matrices facilitated tissue incorporation and infection 
resolution without foreign-body complications [9]. 
Collectively, this body of evidence underscores the biological consistency of HPTC scaffolds 
across diverse tissue environments, suggesting potential applicability beyond surface wounds 
to deeper soft-tissue defects. The breast excision cavity following BCS represents a uniquely 
suitable target for such regenerative scaffolds, as it requires immediate volume support, 
predictable integration, compatibility with adjuvant radiotherapy, and preservation of 
imaging interpretability for cancer surveillance [10,11]. 
Despite encouraging preclinical and early clinical data on collagen-based fillers for soft-
tissue reconstruction, prospective human studies evaluating HPTC scaffolds specifically for 
breast volume restoration after BCS remain limited [12, 13]. Furthermore, standardized 
radiologic and volumetric outcome measures assessing scaffold integration and volume 

maintenance in the breast are lacking. Addressing these gaps is essential to establish the 
clinical role of regenerative scaffolds within oncoplastic breast surgery. 
The present prospective, multicenter clinical trial was therefore designed to evaluate the 
safety, efficacy, radiologic integration, volumetric stability, cosmetic outcomes, and patient-
reported satisfaction associated with implantation of a high-purity Type I collagen scaffold 
for immediate volume restoration following breast-conserving surgery. By integrating 
objective imaging-based metrics with validated patient-reported outcomes, this study aims to 
provide comprehensive evidence supporting the use of HPTC scaffolds as a regenerative 
alternative to conventional volume-replacement techniques in breast cancer surgery. 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 

MATERIALS AND METHODS 
Study Design and Setting 
This prospective, single-arm, multicenter clinical trial was conducted at two tertiary care 
academic institutions in Karnataka, India: JSS Medical College and Hospital, Mysuru. And 
Adichunchanagiri Institute of Medical Sciences (AIMS), B. G. Nagara. The study was 
designed to evaluate the safety, volumetric efficacy, radiologic integration, cosmetic 
outcomes, and patient-reported satisfaction following implantation of a High Purity Type I 
collagen (HPTC) scaffold for immediate volume restoration after breast cancer resection 
surgery. The trial was registered prospectively with ClinicalTrials.gov (ID: NCT07219316) 
and approved by the Institutional Ethics Committee (Approval No.: AIMS/IEC/240/2025). 
The trial was conducted in accordance with the principles of the Declaration of Helsinki and 
Good Clinical Practice guidelines. Approval was obtained from the Institutional Ethics 
Committees of both participating centers prior to patient enrollment. Written informed 
consent was obtained from all participants. The methodological framework, outcome 
hierarchy, and statistical rigor were modeled on previously published multicenter HPTC trials 
to ensure internal validity and reproducibility. 
Patient Selection and Eligibility Criteria 
Women aged 18 to 70 years undergoing BCS for stage 0–II breast carcinoma or high-risk 
premalignant breast lesions were screened for eligibility. Patients were required to have a 
unifocal lesion suitable for wide local excision with an anticipated postoperative breast 
volume deficit of at least 20%, as estimated intraoperatively by the operating surgeon. 
Adequate skin envelope viability and the ability to undergo serial MRI examinations were 
mandatory. 
Exclusion criteria included multicentric disease requiring mastectomy, prior radiotherapy to 
the ipsilateral breast, active local or systemic infection, known hypersensitivity to collagen-
based products, autoimmune or connective tissue disorders, uncontrolled systemic illness, 
pregnancy or lactation, and inability to comply with postoperative follow-up or patient-
reported outcome assessments. 
 
 

Sample Size Determination 
This study was designed as a prospective feasibility and early efficacy trial. Sample size was 
determined based on precision estimation for the primary composite endpoint rather than 
traditional hypothesis testing. Assuming a true success rate of 75% (based on oncoplastic 
literature), a sample of 40 patients provides an expected 95% confidence interval width of 
approximately 25%, which was deemed acceptable for preliminary efficacy assessment and 
effect size estimation to inform future definitive trials. The sample size also ensures adequate 
power (>80%) to detect a clinically meaningful difference of 15% in volume retention 
compared to the benchmark of 75%, assuming a standard deviation of 10% and α = 0.05. 
Surgical Technique and Intervention 
All patients underwent standard oncologic breast-conserving surgery performed by 
experienced breast or plastic surgeons at the respective centers. Following tumor excision 
with confirmed hemostasis and margin adequacy, the excision cavity was carefully assessed 
for volume deficit and three-dimensional geometry. 
A high purity Type I collagen scaffold was trimmed intraoperatively to conform precisely to 
the dimensions of the surgical cavity and implanted without tension. The scaffold was 
positioned in direct contact with surrounding viable breast tissue to facilitate cellular 
infiltration and neovascularization. No additional fixation beyond absorbable sutures was 
routinely required. Layered parenchymal and skin closure was performed using standard 
techniques. The use of surgical drains was left to the discretion of the operating surgeon 
based on oncologic considerations rather than scaffold placement. 
Postoperative management, including antibiotics, wound care, chemotherapy, and 
radiotherapy, followed institutional breast cancer treatment protocols. 
Outcome Measures 
Primary Outcome: Breast Volume Restoration Success 
The primary efficacy endpoint was breast volume restoration success at two months 
postoperatively, defined as a composite outcome incorporating both objective volumetric 
preservation and patient-perceived cosmetic satisfaction. Success required achievement of at 
least 80% objective breast volume retention relative to the immediate postoperative baseline, 
together with a patient satisfaction score of ≥7 on a 10-point Likert scale. This composite 

endpoint was selected to ensure that structural volume preservation translated into clinically 
meaningful cosmetic benefit and patient acceptance. 
Objective Breast Volume Retention 
Objective breast volume retention was assessed using a dual-modality approach comprising 
three-dimensional surface photogrammetry and magnetic resonance imaging (MRI) 
volumetry. Baseline measurements were obtained within 48 hours postoperatively and 
repeated at 2, 4, and 8 weeks. Breast volumes were calculated for the operated breast and 
normalized against the immediate postoperative volume to derive percentage volume 
retention. MRI volumetry served as the reference standard, while 3D surface imaging 
provided adjunctive validation and assessment of symmetry. 
Volume retention was expressed as a continuous variable and analyzed longitudinally to 
assess temporal stability and controlled scaffold resorption. 
MRI Integration Score (MIS) 
Radiologic integration of the HPTC scaffold was evaluated using a predefined MRI 
Integration Score (MIS), a composite semi-quantitative scoring system developed to assess 
biological scaffold performance. MRI examinations were performed immediately 
postoperatively and at 4 and 8 weeks using standardized T1-weighted, T2-weighted, and 
dynamic contrast-enhanced sequences. 
The MIS evaluated four domains: scaffold–host tissue integration, neovascularization based 
on enhancement patterns, scaffold resorption and volume replacement, and tissue quality 
within the scaffold region. Each domain was scored from 0 to 3, yielding a total score ranging 
from 0 to 12, with higher scores indicating superior integration and regenerative remodeling. 
Cosmetic Outcome: BREAST-Q 
Cosmetic outcomes were assessed using the BREAST-Q questionnaire [14], a validated 
patient-reported outcome measure specific to breast surgery. The “Satisfaction with Breasts” 
domain was prespecified as the primary cosmetic endpoint. Questionnaires were administered 
preoperatively and at 4 and 8 weeks postoperatively. Raw scores were converted to 
standardized scores ranging from 0 to 100 according to BREAST-Q scoring manuals, with 
higher scores indicating greater satisfaction [14]. 

Improvement over baseline and attainment of an absolute score ≥70 at final follow-up were 
considered clinically meaningful cosmetic outcomes. 
Safety and Complications 
Safety assessment included prospective recording of all adverse events and postoperative 
complications, including seroma, surgical site infection, hematoma, wound dehiscence, 
scaffold migration or exposure, and delays in adjuvant oncologic therapy. Device-related 
serious adverse events were specifically monitored. All events were managed according to 
institutional protocols and documented throughout the follow-up period. 
Data Collection and Follow-up 
Baseline demographic data, tumor characteristics, operative details, and immediate 
postoperative imaging were recorded at enrollment. Follow-up assessments were conducted 
at 2, 4, and 8 weeks postoperatively, during which volumetric measurements, MRI 
evaluation, BREAST-Q questionnaires [14], and complication surveillance were completed. 
Data were recorded in standardized case record forms at both centers to ensure uniformity. 
Statistical Analysis Plan 
Statistical analysis was performed using IBM SPSS Statistics (version 28.0). Continuous 
variables were summarized as mean ± standard deviation, while categorical variables were 
expressed as frequencies and percentages. Longitudinal changes in breast volume retention, 
MRI Integration Score, and BREAST-Q scores were analyzed using repeated-measures 
analysis of variance. One-sample t-tests were used to compare observed volume retention 
against predefined clinical benchmarks. Correlations between objective volumetric outcomes 
and patient-reported satisfaction were assessed using Pearson correlation coefficients. A two-
sided p value of less than 0.05 was considered statistically significant.