Translating Ideas into Commercial Biomaterial Devices: A Path to Improving Healthcare.

The medical device industry is undergoing substantial transformations, looking to face the increasing pressures on healthcare systems and fundamental shifts in healthcare delivery. There is an ever-growing emphasis on identifying underserved clinical requirements and enhancing industry-academia partnerships to accelerate innovative solutions. In this context, an analysis of the requirements for translation, highlighting support and funding for innovation to transform an idea for a biomaterial device into a commercially available product, is discussed.

Engineering 3D-Printed Bioresorbable Scaffold to Improve Non-Vascularized Fat Grafting: A Proof-of-Concept Study.

Autologous fat grafting is the gold standard for treatment in patients with soft-tissue defects. However, the technique has a major limitation of unpredictable fat resorption due to insufficient blood supply in the initial phase after transplantation. To overcome this problem, we investigated the capability of a medical-grade poly L-lactide-co-poly ε-caprolactone (PLCL) scaffold to support adipose tissue and vascular regeneration. Deploying FDM 3D-printing, we produced a bioresorbable porous scaffold with interconnected pore networks to facilitate nutrient and oxygen diffusion. The compressive modulus of printed scaffold mimicked the mechanical properties of native adipose tissue. In vitro assays demonstrated that PLCL scaffolds or their degradation products supported differentiation of preadipocytes into viable mature adipocytes under appropriate induction. Interestingly, the chorioallantoic membrane assay revealed vascular invasion inside the porous scaffold, which represented a guiding structure for ingrowing blood vessels. Then, lipoaspirate-seeded scaffolds were transplanted subcutaneously into the dorsal region of immunocompetent rats (n = 16) for 1 or 2 months. The volume of adipose tissue was maintained inside the scaffold over time. Histomorphometric evaluation discovered small- and normal-sized perilipin+ adipocytes (no hypertrophy) classically organized into lobular structures inside the scaffold. Adipose tissue was surrounded by discrete layers of fibrous connective tissue associated with CD68+ macrophage patches around the scaffold filaments. Adipocyte viability, assessed via TUNEL staining, was sustained by the presence of a high number of CD31-positive vessels inside the scaffold, confirming the CAM results. Overall, our study provides proof that 3D-printed PLCL scaffolds can be used to improve fat graft volume preservation and vascularization, paving the way for new therapeutic options for soft-tissue defects.

Preclinical Study of Radiation on Fat Flap Regeneration under Tissue-engineering Chamber: Potential Consequences for Breast Reconstruction.

Use of a tissue-engineering chamber (TEC) for growth of fat flap is a promising approach for breast reconstruction. Here, we evaluated in a preclinical model the effects of radiation on adipose tissue growth either before or after 3D-printed bioresorbable TEC implantation. Methods: Twenty-eight female Wistar rats were distributed into three groups: TEC implantation as nonirradiated controls (G1), TEC insertion followed by irradiation 3 weeks later (G2), and irradiation 6 weeks before TEC insertion (G3). G2 and G3 received 33.3 Gy in nine sessions of 3.7 Gy. Growth of the fat flap was monitored via magnetic resonance imaging. At 6 months after implantation, fat flaps and TECs were harvested for analysis. Results: Irradiation did not alter the physicochemical features of poly(lactic-co-glycolic acid)-based TECs. Compared with G1, fat flap growth was significantly reduced by 1.6 times in irradiated G2 and G3 conditions. In G2 and G3, fat flaps consisted of mature viable adipocytes sustained by CD31+ vascular cells. However, 37% (3 of 8) of the G2 irradiated adipose tissues presented a disorganized architecture invaded by connective tissues with inflammatory CD68 + cells, and the presence of fibrosis was observed. Conclusions: Overall, this preclinical study does not reveal any major obstacle to the use of TEC in a radiotherapy context. Although irradiation reduces the growth of fat flap under the TEC by reducing adipogenesis and inducing inconsistent fibrosis, it does not impact flap survival and vascularization. These elements must be taken into account if radiotherapy is proposed before or after TEC-based breast reconstruction.

Effects of Two Melt Extrusion Based Additive Manufacturing Technologies and Common Sterilization Methods on the Properties of a Medical Grade PLGA Copolymer.

Although bioabsorbable polymers have garnered increasing attention because of their potential in tissue engineering applications, to our knowledge there are only a few bioabsorbable 3D printed medical devices on the market thus far. In this study, we assessed the processability of medical grade Poly(lactic-co-glycolic) Acid (PLGA)85:15 via two additive manufacturing technologies: Fused Filament Fabrication (FFF) and Direct Pellet Printing (DPP) to highlight the least destructive technology towards PLGA. To quantify PLGA degradation, its molecular weight (gel permeation chromatography (GPC)) as well as its thermal properties (differential scanning calorimetry (DSC)) were evaluated at each processing step, including sterilization with conventional methods (ethylene oxide, gamma, and beta irradiation). Results show that 3D printing of PLGA on a DPP printer significantly decreased the number-average molecular weight (Mn) to the greatest extent (26% Mn loss, p < 0.0001) as it applies a longer residence time and higher shear stress compared to classic FFF (19% Mn loss, p < 0.0001). Among all sterilization methods tested, ethylene oxide seems to be the most appropriate, as it leads to no significant changes in PLGA properties. After sterilization, all samples were considered to be non-toxic, as cell viability was above 70% compared to the control, indicating that this manufacturing route could be used for the development of bioabsorbable medical devices. Based on our observations, we recommend using FFF printing and ethylene oxide sterilization to produce PLGA medical devices.

Rationale for the design of 3D-printable bioresorbable tissue-engineering chambers to promote the growth of adipose tissue.

Tissue engineering chambers (TECs) bring great hope in regenerative medicine as they allow the growth of adipose tissue for soft tissue reconstruction. To date, a wide range of TEC prototypes are available with different conceptions and volumes. Here, we addressed the influence of TEC design on fat flap growth in vivo as well as the possibility of using bioresorbable polymers for optimum TEC conception. In rats, adipose tissue growth is quicker under perforated TEC printed in polylactic acid than non-perforated ones (growth difference 3 to 5 times greater within 90 days). Histological analysis reveals the presence of viable adipocytes under a moderate (less than 15% of the flap volume) fibrous capsule infiltrated with CD68+ inflammatory cells. CD31-positive vascular cells are more abundant at the peripheral zone than in the central part of the fat flap. Cells in the TEC exhibit a specific metabolic profile of functional adipocytes identified by 1H-NMR. Regardless of the percentage of TEC porosity, the presence of a flat base allowed the growth of a larger fat volume (p < 0.05) as evidenced by MRI images. In pigs, bioresorbable TEC in poly[1,4-dioxane-2,5-dione] (polyglycolic acid) PURASORB PGS allows fat flap growth up to 75 000 mm3 at day 90, (corresponding to more than a 140% volume increase) while at the same time the TEC is largely resorbed. No systemic inflammatory response was observed. Histologically, the expansion of adipose tissue resulted mainly from an increase in the number of adipocytes rather than cell hypertrophy. Adipose tissue is surrounded by perfused blood vessels and encased in a thin fibrous connective tissue containing patches of CD163+ inflammatory cells. Our large preclinical evaluation defined the appropriate design for 3D-printable bioresorbable TECs and thus opens perspectives for further clinical applications.