Sakib F. Elahi

Background: Breast reconstruction commonly employs implantable biomaterials—including poly-4-hydroxybutyrate (P4HB), polypropylene, silicone, and acellular dermal matrix (ADM)—to reinforce soft tissue. These materials differ in composition, degradation profile, and structure, and their potential influence on residual tumor cell behavior remains incompletely understood. Objectives: The objective of the present study was to compare the effects of four biomaterials used in breast reconstruction on the engraftment, tumor area, and proliferation of breast cancer cells in a preclinical model. Methods: Three human breast cancer cell lines (MCF-7, BT-474, and MDA-MB-231) and one non-malignant breast epithelial cell line (MCF-10A) were co-implanted with P4HB scaffold, polypropylene mesh, silicone, or porcine acellular dermal matrix (ADM) in NSG™ mice, using Matrigel, human Adipose Graft, or extracellular matrix (ECM) gel to simulate distinct tissue microenvironments. At six weeks, engraftment, tumor area, and proliferation were assessed histologically. Results: Tumors formed only with malignant cell lines; no engraftment occurred with MCF-10A or cell-free controls. Tumor area varied by cell line, vehicle, and biomaterial: Polypropylene was most frequently associated with the largest tumor areas, particularly for the more aggressive MDA-MB-231 cell line, while ADM was generally associated with smaller tumor areas. However, no single biomaterial consistently increased tumor area or proliferation across all cell lines and vehicles, and proliferation scores showed few significant differences between the evaluated groups. Conclusions: The findings from this model suggest that residual tumor growth may not be largely influenced by the presence of a specific biomaterial. These results provide preliminary, model-specific reassurance regarding the biomaterials evaluated here, but do not, on their own, establish the oncologic safety of these devices in the clinical setting of breast reconstruction, underscoring the need for further studies in clinically representative models.

Background: Absorbable scaffolds such as poly-4-hydroxybutyrate (P4HB) are increasingly used in aesthetic breast surgery to support implants. However, the nature and timing of scaffold–implant interactions during early healing remain uncharacterized. Objectives: Evaluate whether contact between P4HB Scaffolds and silicone implants can cause mechanical weaking of either device or wear-related particulate generation. Methods: Two independent studies were performed. An animal study assessed early P4HB Scaffold-tissue integration. Characteristics and histology of scaffold explants were compared to native capsules after 4 weeks in a porcine silicone implant model. A separate benchtop study evaluated scaffold and implant mechanical integrity and particulate generation after interactive cyclic loading for 12 weeks, exceeding the in vivo integration period, to conservatively evaluate interaction. Mechanical testing was performed of implants and scaffolds after interaction and compared to non-tested devices. Particulate analysis was performed on fluid collected from the bench apparatus. Results: Scaffold-tissue capsules show surface characteristics similar to native tissue capsules, indicating complete integration at 4-weeks. After 12-week benchtop loading, mechanical properties of scaffolds and implants were comparable to controls and met standard specifications for new devices. Particulates were below detection limits. Conclusions: This preclinical study evaluated early scaffold–implant interaction during the period of maximal direct polymer contact and assessed mechanical interactions under worst-case simulated conditions. By 4 weeks in animals, tissue integration limits direct polymer–implant contact. After 12 weeks on the bench, no compromise of implant or scaffold mechanical integrity or detectable particulates were observed under the tested conditions. These findings provide preliminary data and do not address long-term effects.

Background: Poly-4-hydroxybutyrate (P4HB) scaffolds are increasingly used to reinforce soft tissue during implant-based reconstruction after mastectomy. P4HB undergoes hydrolytic degradation to a natural metabolite, 4-hydroxybutyrate (4HB). Understanding the direct effects of 4HB on cancer cells is essential for assessing the oncologic safety of P4HB scaffolds used in breast reconstruction surgery. The aim of this study was to evaluate the effects of sodium 4-hydroxybutyrate (Na4HB) on multiple, relevant human breast cancer and epithelial cell types using a panel of well-established in vitro assays aligned with several hallmarks of cancer. Methods: First, the clinically relevant tissue concentration of 4HB was determined via a rabbit model to quantify 4HB in the peri-implant tissue of P4HB scaffolds. Second, human breast cell types, including non-malignant HMEC and MCF-10A, and cancerous MCF-7, BT-474 and MDA-MB-231, were exposed to Na4HB at up to 10X the clinically relevant tissue concentration. Cells were then evaluated for cancer related phenotypes: metabolic activity (MTT assay), proliferation (BrdU assay), migration (Scratch and Transwell assays), and colony formation (soft agar assays). Specific inhibitory control compounds for each assay were included to confirm assay performance. Results: The average peri-implant concentration of 4HB was found to be 163 µM after a simulated 1-year implantation in a rabbit model. Across the five assays and all three Na4HB concentrations, ranging from below to over 10X the peri-implant level (70, 350, 1750 µM), there was no statistically significant increase in any cancer-related phenotype including metabolic activity, proliferation, migration and colony formation in either malignant or non-malignant cell types compared to controls treated with either the PBS vehicle or sodium acetate as determined by one-way ANOVA followed by Tukey’s multiple comparison test ( p > 0.05). Conclusions: This comprehensive, in vitro evaluation suggests that 4HB does not modify growth or activity of malignant or non-malignant breast cells at concentrations up to 10X the peri-implant level. While these findings suggest that 4HB released from degrading P4HB Scaffolds is unlikely to promote oncogenic behavior in vitro, further co-culture systems, in vivo studies and long-term clinical data can be used to further assess the oncologic safety in breast reconstruction.

Background/Objectives: The porcine mammary anatomy is poorly characterized, and structures are difficult to differentiate macroscopically, unlike human mammary tissue. The objective of this exploratory study was to describe the Yucatan porcine breast tissue morphology and identify the basic differences and similarities to human breast tissue. Methods: Samples from an adult, non-parous female Yucatan pig were prepared utilizing various methods: freezing at −80 °F (−26.67 °C) with a thickness of 0.5 cm/post-fixation in formalin; freezing at −20 °F (−6.67 °C) with a thickness of 0.5 cm/post-fixation in formalin; or formalin fixed and incised at ~0.8 cm. A descriptive comparison of the gross and microscopic images of the porcine breast morphology to the previously described human breast anatomy was performed. Results: As examined grossly, frozen sections allowed narrower serial cross-sectioning and better visualization of the structures and relationships. The mammary glands were poorly demarcated with extensive interspersed adipose tissue throughout the periphery. The mammary tissue appeared grossly as pigmented tissue and extended within ~0.5 cm from the skin surface, ~2.0 cm deep (within ~0.5 cm of the deep muscle layer), and ~6.5 cm laterally (centered on a teat). There were a number of similarities between Yucatan porcine and human breast tissue, yet there were several inherent structural differences. In contrast to human mammary tissue, porcine mammary glands consist of more diffuse acinar tissue, less well demarcated by defined fascial, lamellar, and ligamentous structures. Conclusions: The Yucatan porcine mammary morphology and similarities to the human mammary region allow for the use of this animal model to guide those developing relevant technologies or performing local surgical interventions in the preclinical setting.

Optical biosensing is being actively investigated for minimally-invasive monitoring of key biomarkers both $in~ vitro$ and $in~ vivo$ . However, typical benchtop instruments are not portable and are not well suited to high-throughput, real-time analysis. This paper presents a versatile multichannel instrument for measurement of emission intensity and lifetime values arising from luminescent biosensor materials. A detailed design description of the opto-electronic hardware as well as the control software is provided, elaborating a flexible, user-configurable system that may be customized or duplicated for a wide range of applications. This article presents experimental measurements that prove the $in~ vitro$ and $in ~vivo$ functionality of the system. Such tools may be adopted for many research and development purposes, including evaluation of new biosensor materials, and may also serve as prototypes for future miniaturized handheld or wearable devices.