We have developed three types of materials composed of polyurethane–gelatin, polycaprolactone–gelatin, or polylactic acid–gelatin nanofibers by coaxially electro-spinning the hydrophobic core and gelatin sheath with a ratio of 1:5 at fixed concentrations. Results from attenuated total reflection-Fourier transformed infrared spectroscopy demonstrated the gelatin coating around nanofibers in all of the materials. Transmission electron microscopy images further displayed the core–sheath structures showing the core-to-sheath thickness ratio varied greatly with the highest ratio found in polyurethane-gelatin nanofibers. Scanning electron microscopy images revealed similar, uniform fibrous structures in all of the materials, which changed with genipin cross-linking due to interfiber interactions. Thermal analyses revealed varied interactions between the hydrophilic sheath and hydrophobic core among the three materials, which likely caused different core–sheath structures, and thus physicomechanical properties. The addition of gelatin around the hydrophobic polymer and their interactions led to the formation of graft scaffolds with tissue-like viscoelasticity, high compliance, excellent swelling capability, and absence of water permeability while maintaining competent tensile modulus, burst pressure, and suture retention. The hydrogel-like characteristics are advantageous for vascular grafting use, because of the capability of bypassing preclotting prior to implantation, retaining vascular fluid volume, and facilitating molecular transport across the graft wall, as shown by coculturing vascular cells sandwiched over a thick-wall scaffold. Varied core–sheath interactions within scaffolding nanofibers led to differences in graft functional properties such as water swelling ratio, compliance, and supporting growth of cocultured vascular cells. The PCL–gelatin scaffold with thick gelatin-sheathed nanofibers demonstrated a more compliant structure, elastic mechanics, and high water swelling property. Our results demonstrate a feasible approach to produce new hybrid, biodegradable nanofibrous scaffold biomaterials with interactive core–sheath structure, good biocompatibility, and tissue-like viscoelasticity, which may reduce potential problems with the use of individual polymers for vascular grafts.

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Readily-available small-diameter arterial grafts require a great combination of materials properties, including high strength, compliance, suturability, blood sealing and antithrombogenicity, as well as anti-kinking property for those used in challenging anatomical situations. We have constructed grafts composed of coaxially-structured polycaprolactone (PCL)/ gelatin nanofibres, and tailored the material structures to achieve high strength, compliance and kink resistance, as well as excellent water sealing and anti-thrombogenicity. Coaxially-structured fibres in the grafts provided mechanical stability through the core, while flexibility and cell adhesion through the sheath. Results showed that graft compliance increased while strength decreased with the concentration ratio between core and sheath polymers. Compared to pure PCL fibrous surfaces, coaxial PCL/gelatin fibrous surfaces potently inhibited platelet adhesion and activation, providing excellent anti-thrombogenicity. To render sufficient burst strength and suturability, an additional layer of pure PCL was necessary to cap the layer of coaxial PCL/gelatin fibres. The two-layered grafts with the wall thickness comparable to native arteries demonstrated artery-like compliance and kink resistance, properties important to arteries under complex mechanical loading. The in vivo evaluation was performed using the interposition carotid artery graft model in rabbits for three months. Interestingly, results from ultrasonic imaging and histological analysis demonstrated that the two-layered grafts with a thinner outer PCL layer, which possessed higher compliance and kink resistance, showed increased blood flow, minimal lumen reduction and fibrosis. All vascular grafts exhibited patency and induced limited cell infiltration. Together, we presented a facile and useful approach to fabricate vascular grafts with superior graft performances, biomechanical properties, and blood compatibility. Grafts with artery-like compliance and flexibility have demonstrated improved implantation outcomes.

Current treatment strategies for osteoarthritis (OA) predominantly address symptoms with limited disease-modifying potential. There is a growing interest in the use of adipose-derived stem cells (ADSCs) for OA treatment and developing biomimetic injectable hydrogels as cell delivery systems. Biomimetic injectable hydrogels can simulate the native tissue microenvironment by providing appropriate biological and chemical cues for tissue regeneration. A biomimetic injectable hydrogel using amnion membrane (AM) was developed which can self-assemble in situ and retain the stem cells at the target site. In the present study, we evaluated the efficacy of intraarticular injections of AM hydrogels with and without ADSCs in reducing inflammation and cartilage degeneration in a collagenase-induced OA rat model. A week after the induction of OA, rats were treated with control (phosphate-buffered saline), ADSCs, AM gel, and AM-ADSCs. Inflammation and cartilage regeneration was evaluated by joint swelling, analysis of serum by cytokine profiling and Raman spectroscopy, gross appearance, and histology. Both AM and ADSC possess antiinflammatory and chondroprotective properties to target the sites of inflammation in an osteoarthritic joint, thereby reducing the inflammation-mediated damage to the articular cartilage. The present study demonstrated the potential of AM hydrogel to foster cartilage tissue regeneration, a comparable regenerative effect of AM hydrogel and ADSCs, and the synergistic antiinflammatory and chondroprotective effects of AM and ADSC to regenerate cartilage tissue in a rat OA model.

In this study, we developed three-dimensional (3D) printed annular ring-like scaffolds of hydrogel (gelatin–alginate) constructs encapsulated with a mixture of human cardiac AC16 cardiomyocytes (CMs), fibroblasts (CFs), and microvascular endothelial cells (ECs) as cardiac organoid models in preparation for investigating the role of microgravity in cardiovascular disease initiation and development. We studied the mechanical properties of the acellular scaffolds and confirmed their cell compatibility as well as heterocellular coupling for cardiac tissue engineering. Rheological analysis performed on the acellular scaffolds showed the scaffolds to be elastogenic with elastic modulus within the range of a native in vivo heart tissue. The microstructural and physicochemical properties of the scaffolds analyzed through scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy-attenuated total reflectance (ATR-FTIR) confirmed the mechanical and functional stability of the scaffolds for long-term use in in vitro cell culture studies. HL-1 cardiomyocytes bioprinted in these hydrogel scaffolds exhibited contractile functions over a sustained period of culture. Cell mixtures containing CMs, CFs, and ECs encapsulated within the 3D printed hydrogel scaffolds exhibited a significant increase in viability and proliferation over 21 days, as shown by flow cytometry analysis. Moreover, via the expression of specific cardiac biomarkers, cardiac-specific cell functionality was confirmed. Our study depicted the heterocellular cardiac cell interactions, which is extremely important for the maintenance of normal physiology of the cardiac wall in vivo and significantly increased over a period of 21 days in in vitro. This 3D bioprinted “cardiac organoid” model can be adopted to simulate cardiac environments in which cellular crosstalk in diseased pathologies like cardiac atrophy can be studied in vitro and can further be used for drug cytotoxicity screening or underlying disease mechanisms.

Since the first work by Laurencin and colleagues on the development of polymeric electrospinning for biomedical purposes, the use of electrospinning technology has found broad applications in such areas of tissue regeneration and drug delivery. More recently, coaxial electrospinning has emerged as an important technique to develop scaffolds for regenerative engineering incorporated with drug(s). However, the addition of a softer core layer leads to a reduction in mechanical properties. Here, novel robust tripolymeric triaxially electrospun fibrous scaffolds were developed with a polycaprolactone (PCL) (core layer), a 50:50 poly (lactic-co-glycolic acid) (PLGA) (sheath layer) and a gelatin (intermediate layer) with a dual drug delivery capability was developed through modified electrospinning. A sharp increase in elastic modulus after the incorporation of PCL in the core of the triaxial fibers in comparison with uniaxial PLGA (50:50) and coaxial PLGA (50:50) (sheath)-gelatin (core) fibers was observed. Thermal analysis of the fibrous scaffolds revealed an interaction between the core-intermediate and sheath-intermediate layers of the triaxial fibers contributing to the higher tensile modulus. A simultaneous dual release of model small molecule Rhodamine B (RhB) and model protein Fluorescein isothiocynate (FITC) Bovine Serum Albumin (BSA) conjugate incorporated in the sheath and intermediate layers of triaxial fibers was achieved. The tripolymeric, triaxial electrospun systems were seen to be ideal for the support of mesenchymal stem cell growth, as shrinkage of fibers normally found with conventional electrospun systems was minimized. These tripolymeric triaxial electrospun fibers that are biomechanically competent, biocompatible, and capable of dual drug release are designed for regenerative engineering and drug delivery applications.