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1. Degradation and Mechanical Behavior of Fish Gelatin/Polycaprolactone AC Electrospun Nanofibrous Meshes

   https://doi.org/10.1002/mame.202300106  

   Lacy, Hannah A.; Nealy, Sarah L.; Stanishevsky, Andrei (July 2023, Macromolecular Materials and Engineering)

   Abstract With the increasing interest in biopolymer nanofibers for diverse applications, the characterization of these materials in the physiological environment has become of equal interest and importance. This study performs first‐time simulated body fluid (SBF) degradation and tensile mechanical analyses of blended fish gelatin (FGEL) and polycaprolactone (PCL) nanofibrous meshes prepared by a high‐throughput free‐surface alternating field electrospinning. The thermally crosslinked FGEL/PCL nanofibrous materials with 84–96% porosity and up to 60 wt% PCL fraction demonstrate mass retention up to 88.4% after 14 days in SBF. The trends in the PCL crystallinity and FGEL secondary structure modification during the SBF degradation are analyzed by Fourier transform infrared spectroscopy. Tensile tests of such porous, 0.1–2.2 mm thick FGEL/PCL nanofibrous meshes in SBF reveal the ultimate tensile strength, Young's modulus, and elongation at break within the ranges of 60–105 kPa, 0.3–1.6 MPa, and 20–70%, respectively, depending on the FGEL/PCL mass ratio. The results demonstrate that FGEL/PCL nanofibrous materials prepared from poorly miscible FGEL and PCL can be suitable for selected biomedical applications such as scaffolds for skin, cranial cruciate ligament, articular cartilage, or vascular tissue repair. 

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2. Incorporating nanoconfined chitin ‐ fibrils in poly (ε‐caprolactone) membrane scaffolds improves mechanical and chemical properties for biomedical application

   https://doi.org/10.1002/jbm.a.37507  

   Saudi, Sheikh; Jun, Sunghyun; Fialkova, Svitlana; Surendran, Vikram; Chandrasekaran, Arvind; Bhattarai, Shanta R.; Sankar, Jagannathan; Bhattarai, Narayan (January 2023, Journal of Biomedical Materials Research Part A)

   Abstract Engineered composite scaffolds composed of natural and synthetic polymers exhibit cooperation at the molecular level that closely mimics tissue extracellular matrix's (ECM) physical and chemical characteristics. However, due to the lack of smooth intermix capability of natural and synthetic materials in the solution phase, bio‐inspired composite material development has been quite challenged. In this research, we introduced new bio‐inspired material blending techniques to fabricate nanofibrous composite scaffolds of chitin nanofibrils (CNF), a natural hydrophilic biomaterial and poly (ɛ‐caprolactone) (PCL), a synthetic hydrophobic‐biopolymer. CNF was first prepared by acid hydrolysis technique and dispersed in trifluoroethanol (TFE); and second, PCL was dissolved in TFE and mixed with the chitin solution in different ratios. Electrospinning and spin‐coating technology were used to form nanofibrous mesh and films, respectively. Physicochemical properties, such as mechanical strength, and cellular compatibility, and structural parameters, such as morphology, and crystallinity, were determined. Toward the potential use of this composite materials as a support membrane in blood–brain barrier application (BBB), human umbilical vein endothelial cells (HUVECs) were cultured, and transendothelial electrical resistance (TEER) was measured. Experimental results of the composite materials with PCL/CNF ratios from 100/00 to 25/75 showed good uniformity in fiber morphology and suitable mechanical properties. They retained the excellent ECM‐like properties that mimic synthetic‐bio‐interface that has potential application in biomedical fields, particularly tissue engineering and BBB applications. 

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3. 3D printing of PCL-ceramic composite scaffolds for bone tissue engineering applications

   https://doi.org/10.36922/ijb.0196  

   Kumar_Parupelli, Santosh; Saudi, Sheikh; Bhattarai, Narayan; Desai, Salil (October 2023, International Journal of Bioprinting)

   Three-dimensional (3D) printing was utilized for the fabrication of a composite scaffold of poly(ε-caprolactone) (PCL) and calcium magnesium phosphate (CMP) bioceramics for bone tissue engineering application. Four groups of scaffolds, that is, PMC-0, PMC-5, PMC-10, and PMC-15, were fabricated using a custom 3D printer. Rheology analysis, surface morphology, and wettability of the scaffolds were characterized. The PMC-0 scaffolds displayed a smoother surface texture and an increase in the ceramic content of the composite scaffolds exhibited a rougher structure. The hydrophilicity of the composite scaffold was significantly enhanced compared to the control PMC-0. The effect of ceramic content on the bioactivity of fibroblast NIH/3T3 cells in the composite scaffold was investigated. Cell viability and toxicity studies were evaluated by comparing results from lactate dehydrogenase (LDH) and Alamar Blue (AB) colorimetric assays, respectively. The live-dead cell assay illustrated the biocompatibility of the tested samples with more than 100% of live cells on day 3 compared to the control one. The LDH release indicated that the composite scaffolds improved cell attachment and proliferation. In this research, the fabrication of a customized composite 3D scaffold not only mimics the rough textured architecture, porosity, and chemical composition of natural bone tissue matrices but also serves as a source for soluble ions of calcium and magnesium that are favorable for bone cells to grow. These 3D-printed scaffolds thus provide a desirable microenvironment to facilitate biomineralization and could be a new effective approach for preparing constructs suitable for bone tissue engineering. 

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4. Gradient scaffolds for osteochondral tissue engineering and regeneration

   https://doi.org/10.1039/D0TB00688B  

   Zhang, Bin; Huang, Jie; Narayan, Roger J. (September 2020, Journal of Materials Chemistry B)

   null (Ed.)

   The tissue engineering approach for repairing osteochondral (OC) defects involves the fabrication of a biological tissue scaffold that mimics the physiological properties of natural OC tissue ( e.g. , the gradient transition between the cartilage surface and the subchondral bone). The OC tissue scaffolds described in many research studies exhibit a discrete gradient ( e.g. , a biphasic or tri/multiphasic structure) or a continuous gradient to mimic OC tissue attributes such as biochemical composition, structure, and mechanical properties. One advantage of a continuous gradient scaffold over biphasic or tri/multiphasic tissue scaffolds is that it more closely mimics natural OC tissue since there is no distinct interface between each layer. Although research studies to this point have yielded good results related to OC regeneration with tissue scaffolds, differences between engineered scaffolds and natural OC tissue remain; due to these differences, current clinical therapies to repair OC defects with engineered scaffolds have not been successful. This paper provides an overview of both discrete and continuous gradient OC tissue scaffolds in terms of cell type, scaffold material, microscale structure, mechanical properties, fabrication methods, and scaffold stimuli. Fabrication of gradient scaffolds with three-dimensional (3D) printing is given special emphasis due to its ability to accurately control scaffold pore geometry. Moreover, the application of computational modeling in OC tissue engineering is considered; for example, efforts to optimize the scaffold structure, mechanical properties, and physical stimuli generated within the scaffold–bioreactor system to predict tissue regeneration are considered. Finally, challenges associated with the repair of OC defects and recommendations for future directions in OC tissue regeneration are proposed. 

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5. Investigating the Effect of Aligned Microtube Density on the Mechanical Strength of Hydrogel Scaffolds

   https://doi.org/10.1115/MSEC2024-125393  

   Halder, Sampa; Qavi, Imtiaz; Tan, George (June 2024, American Society of Mechanical Engineers)

   Abstract Tissue engineering is a pivotal research domain, central to advancing biomedical manufacturing processes with the aim of fabricating functional artificial organs and tissues. Addressing the pressing concern of organ shortages and myriad medical challenges necessitates innovative manufacturing techniques. Hydrogel scaffolds, due to their biocompatibility and extracellular matrix-mimicking porous structure, have emerged as prime candidates in this arena. Moreover, their hygroscopic properties and tunable mechanical characteristics render them suitable for various tissue engineering applications. Despite their promising attributes, a significant manufacturing challenge persists: the optimization of cellular growth within the confines of hydrogel scaffolds. Effective vascularization, essential for optimal cellular nutrient and oxygen supply, remains elusive. Our previous manufacturing research tackled this, introducing a novel hybrid Bio-Fabrication technique. This technique integrated coaxial electrospinning and extrusion-based bioprinting methodologies, yielding hydrogel scaffolds fortified with microtubes. These strategically embedded microtubes, modeled after capillary structures, function as microchannel diffusion conduits, enhancing cellular viability within the hydrogel matrix. A core aspect of scaffold manufacturing is ensuring the stability of its 3D architecture, especially post-swelling. Preliminary hypotheses suggest a gamut of factors — including microtube shape, size, orientation, alignment, and density — play determinant roles in shaping the scaffold’s mechanical attributes. This research rigorously examines the mechanical evolution of hydrogel scaffolds when supplemented with aligned electrospun microtubes across a spectrum of densities. A blend of sodium alginate (SA) and gelatin was selected for the hydrogel matrix due to their inherent biocompatibility and favorable mechanical properties. Different concentrations were prepared to assess the optimal mixture for mechanical stability. A co-axial electrospinning setup was employed where polycaprolactone (PCL) was used as the sheath material and polyethylene oxide (PEO) functioned as the core. This dual material approach was intended to leverage the structural rigidity of PCL with the biodegradability of PEO. The spinning parameters, including voltage, flow rate, and tip-to-collector distance, were meticulously adjusted to produce aligned microtubes of varied densities and diameters. Once the microtubes were synthesized, they were layered within the hydrogel constructs. The layering process involved depositing a hydrogel layer, positioning the microtubes, and then sealing with another hydrogel layer. The entire structure was then solidified using calcium chloride, resulting in a robust, multi-layered composite. Post-fabrication, the hydrogel scaffolds underwent mechanical evaluations. Compression tests were employed to measure the compressive modulus. Tensile tests were conducted to determine ultimate tensile strength. These tests were crucial to understanding the impact of microtube density on the overall mechanical properties of the hydrogel scaffolds. The high-density group, while showing improved mechanical properties over the control group, did not surpass the low-density group, suggesting a possible saturation point. In conclusion, our research methodically explored the influence of microtube density on the mechanical and structural attributes of hydrogel scaffolds. The manufacturing insights gleaned hold substantive implications, promising to propel the field of tissue engineering and drive transformative advancements in biomedical manufacturing. 

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