Strategies for improving the 3D printability of decellularized extracellular matrix bioink.

3D bioprinting is a revolutionary technology capable of replicating native tissue and organ microenvironments by precisely placing cells into 3D structures using bioinks. However, acquiring the ideal bioink to manufacture biomimetic constructs is challenging. A natural extracellular matrix (ECM) is an organ-specific material that provides physical, chemical, biological, and mechanical cues that are hard to mimic using a small number of components. Organ-derived decellularized ECM (dECM) bioink is revolutionary and has optimal biomimetic properties. However, dECM is always "non-printable" owing to its poor mechanical properties. Recent studies have focused on strategies to improve the 3D printability of dECM bioink. In this review, we highlight the decellularization methods and procedures used to produce these bioinks, effective methods to improve their printability, and recent advances in tissue regeneration using dECM-based bioinks. Finally, we discuss the challenges associated with manufacturing dECM bioinks and their potential large-scale applications.

Polydopamine modified acellular dermal matrix sponge scaffold loaded with a-FGF: Promoting wound healing of autologous skin grafts.

Despite increasing potentials as a skin regeneration template (DRT) to guide tissue healing, acellular dermal matrix (ADM) is still challenged by issues (like dense architecture, low cellular adhesion and poor vascularization), contributing to necrosis and shedding of upper transplanted skins. Modified with polydopamine (PDA), a novel and porous DRT capable of drug delivery was designed using porcine-derived ADM (PADMS) gels, termed PDA-PADMS. However, it was unclear whether it could efficiently deliver human acidic fibroblast growth factor (a-FGF) and regenerate skin defects. Herein, after being fabricated and optimized with PADMS gels in different ratios (1:6, 1:7, 1:8), PDA-PADMS loading a-FGF (PDA-PADMS-FGF) was evaluated by the morphology, physical& chemical properties, drug release and in-vitro biological evaluations, followed by full-thickness skin defects implanted with PDA-PADMS-FGF covered by transplanted skins. Apart from containing abundant collagen and elastin, porous PADMS (with a loose and uniform structure) was demonstrated to possess controlled release of a-FGF and biocompatibility attributed to PDA coating. Consistent with augmented cellular migration and proliferation in vitro, PDA-PADMS-FGF also accelerated wound healing and reduced scarring, improving collagen arrangement and neovascularization. In conclusion, PDA-PADMS-FGF has a good potential and application prospect as a matrix material for wound repair.

A Randomized Trial Comparing the NeoVas Sirolimus-Eluting Bioresorbable Scaffold and Metallic Everolimus-Eluting Stents.

OBJECTIVES: The authors sought to evaluate the safety and effectiveness of the NeoVas bioresorbable scaffold (BRS) compared with metallic drug-eluting stents. BACKGROUND: BRS have the potential to improve very late outcomes compared with metallic drug-eluting stents, but some BRS have been associated with increased rates of device thrombosis before complete bioresorption. NeoVas is a new poly-l-lactic acid BRS that elutes sirolimus from a poly-D, l-lactide coating. METHODS: Eligible patients with a single de novo native coronary artery lesion with a reference vessel diameter 2.5 to 3.75 mm and a lesion length ≤20 mm were randomized 1:1 to NeoVas BRS versus cobalt-chromium everolimus-eluting stents (CoCr-EES). Angiographic follow-up was performed in all patients at 1 year. The primary endpoint was angiographic in-segment late loss (LL), and the major secondary endpoint was the rate of angina. Baseline and follow-up optical coherence tomography and fractional flow reserve were performed in a pre-specified subgroup of patients. RESULTS: The authors randomized 560 patients at 32 centers to treatment with NeoVas (n = 278) versus CoCr-EES (n = 282). One-year in-segment LL with NeoVas and CoCr-EES were 0.14 ± 0.36 mm versus 0.11 ± 0.34 mm (difference 0.03 mm; upper 1-sided 97.5% confidence interval 0.09 mm; pnoninferiority < 0.0001; psuperiority = 0.36). Clinical outcomes at 1 year were similar in the 2 groups, as were the rates of recurrent angina (27.9% vs. 32.1%; p = 0.26). Optical coherence tomography at 1 year demonstrated a higher proportion of covered struts (98.7% vs. 96.2%; p < 0.001), less strut malapposition (0% vs. 0.6%; p <0.001), and a smaller minimal lumen area (4.71 ± 1.64 vs. 6.00 ± 2.15 mm2; p < 0.001) with NeoVas compared with CoCr-EES respectively, with nonsignificant differences in fractional flow reserve (0.89 ± 0.08 vs. 0.91 ± 0.06; p = 0.07). CONCLUSIONS: The NeoVas BRS was noninferior to CoCr-EES for the primary endpoint of 1-year angiographic in-segment LL, and resulted in comparable 1-year clinical outcomes, including recurrent angina. (NeoVas Bioresorbable Coronary Scaffold Randomized Controlled Trial; NCT02305485).

Visualizing polymeric bioresorbable scaffolds with three-dimensional image reconstruction using contrast-enhanced micro-computed tomography.

There are no previous studies showing how to visualize polymeric bioresorbable scaffolds (BRSs) by micro-computed tomography (mCT). There are no previous studies showing how to visualize polymeric bioresorbable scaffolds (BRSs) by micro-computed tomography (mCT). This study aimed to explore the feasibility of detecting polymeric BRS with 3-dimensional reconstruction of BRS images by contrast-enhanced mCT and to determine the optimal imaging settings. BRSs, made of poly-L-lactic acid (PLLA), were implanted in coronary bifurcation models. Five treatments were conducted to examine an optimal condition for imaging BRSs: Baseline treatment, samples were filled with normal saline and scanned with mCT immediately; Treatment-1, -2, -3 and -4, samples were filled with contrast medium and scanned with mCT immediately and 1, 2 and 3 h thereafter, corresponding to soaking time of contrast medium of 0, 1, 2 and 3 h. Compared to Baseline, mCT scanning completely discriminate the scaffold struts from the vascular lumen immediately after filling the samples with contrast agent but not from the vascular wall until the contrast agent soaking time was more than 2 h (Treatment-3 and -4). By setting 10-15 HU as a cut-point of CT values, the scaffold strut detectable rate at Baseline and Teatment-1, -2, -3 and -4 were 1.23 ± 0.31%, 1.65 ± 0.26%, 58.14 ± 12.84%, 97.97 ± 1.43% and 98.90 ± 0.38%, respectively (Treatment-3 vs. Treatment-2, p < 0.01); meanwhile, the success rate of 3D BRS reconstruction with high quality images at Baseline and Teatment-1, -2, -3 and -4 were 1.23%, 1.65%, 58.14%, 97.97% and 98.90%, respectively (Treatment-3 vs. Treatment-2, p < 0.01). In conclusions, reconstruction of 3D BRS images is technically feasible by contrast-enhanced mCT and soaking time of contrast agent for more than 2 h is necessary for complete separation of scaffold struts from the surrounding structures in the phantom samples.