Fabrication and in vitro evaluation of 3D composite scaffold based on collagen/hyaluronic acid sponge and electrospun polycaprolactone nanofibers for peripheral nerve regeneration.

Replacement of peripheral nerve autografts with tissue engineered nerve grafts will potentially resolve the lack of nerve tissue especially in patients with severe concomitant soft tissue injuries. This study attempted to fabricate a tissue engineered nerve graft composed of electrospun PCL conduit filled with collagen-hyaluronic acid (COL-HA) sponge with different COL-HA weight ratios including 100:0, 98:2, 95:5 and 90:10. The effect of HA addition on the sponge porosity, mechanical properties, water absorption and degradation rate was assessed. A good cohesion between the electrospun PCL nanofibers and COL-HA sponges were seen in all sponges with different HA contents. Mechanical properties of PCL nanofibrous layer were similar to the rat sciatic nerve; the ultimate tensile strength was 2.23 ± 0.35 MPa at the elongation of 35%. Additionally, Schwann cell proliferation and morphology on three dimensional (3D) composite scaffold were evaluated by using MTT and SEM assays, respectively. Rising the HA content resulted in higher water absorption as well as greater pore size and porosity, while a decrease in Schwann cell proliferation compared to pure collagen sponge, although reduction in cell proliferation was not statistically significant. The lower Schwann cell proliferation on the COL-HA was attributed to the greater degradation rate and pore size of the COL-HA sponges. Also, dorsal root ganglion assay showed that the engineered 3D construct significantly increases axon growth. Taken together, these results suggest that the fabricated 3D composite scaffold provide a permissive environment for Schwann cells proliferation and maturation and can encourage axon growth.

Predicting degradation rate of genipin cross-linked gelatin scaffolds with machine learning.

Genipin can improve weak mechanical properties and control high degradation rate of gelatin, as a cross-linker of gelatin which is widely used in tissue engineering. In this study, genipin cross-linked gelatin biodegradable porous scaffolds with different weight percentages of gelatin and genipin were prepared for tissue regeneration and measurement of their various properties including morphological characteristics, mechanical properties, swelling, degree of crosslinking and degradation rate. Results indicated that the sample containing the highest amount of gelatin and genipin had the highest degree of crosslinking and increasing the percentage of genipin from 0.125% to 0.5% enhances ultimate tensile strength (UTS) up to 113% and 92%, for samples with 2.5% and 10% gelatin, respectively. For these samples, increasing the percentage of genipin, reduce their degradation rate significantly with an average value of 124%. Furthermore, experimental data are used to develop a machine learning model, which compares artificial neural networks (ANN) and kernel ridge regression (KRR) to predict degradation rate of genipin-cross-linked gelatin scaffolds as a property of interest. The predicted degradation rate demonstrates that the ANN, with mean squared error (MSE) of 2.68%, outperforms the KRR with MSE = 4.78% in terms of accuracy. These results suggest that machine learning models offer an excellent prediction accuracy to estimate the degradation rate which will significantly help reducing experimental costs needed to carry out scaffold design.

Design and manufacture of neural tissue engineering scaffolds using hyaluronic acid and polycaprolactone nanofibers with controlled porosity.

Given the large differences in nervous tissue and other tissues of the human body and its unique features, such as poor and/or lack of repair, there are many challenges in the repair process of this tissue. Tissue engineering is one of the most effective approaches to repair neural damages. Scaffolds made from electrospun fibers have special potential in cell adhesion, function and cell proliferation. This research attempted to design a high porous nanofibrous scaffold using hyaluronic acid and polycaprolactone to provide ideal conditions for nerve regeneration by applying proper physicochemical and mechanical signals. Chemical and mechanical properties of pure PCL and PCL/HA nanofibrous scaffolds were measured by FTIR and tensile test. Morphology, swelling behavior, and biodegradability of the scaffolds were evaluated too. Porosity of various layers of scaffolds was measured by image analysis method. To assess the cell-scaffold interaction, SH-SY5Y human neuroblastoma cell line were cultured on the electrospun scaffolds. Taken together, these results suggest that the blended nanofibrous scaffolds PCL/HA 95:5 exhibit the most balanced properties to meet all of the required specifications for neural cells and have potential application in neural tissue engineering.