Hybrid biomanufacturing systems applied in tissue regeneration.

Scaffold-based approach is a developed strategy in biomanufacturing, which is based on the use of temporary scaffold that performs as a house of implanted cells for their attachment, proliferation, and differentiation. This strategy strongly depends on both materials and manufacturing processes. However, it is very difficult to meet all the requirements, such as biocompatibility, biodegradability, mechanical strength, and promotion of cell-adhesion, using only single material. At present, no single bioprinting technique can meet the requirements for tissue regeneration of all scales. Thus, multi-material and mixing-material scaffolds have been widely investigated. Challenges in terms of resolution, uniform cell distribution, and tissue formation are still the obstacles in the development of bioprinting technique. Hybrid bioprinting techniques have been developed to print scaffolds with improved properties in both mechanical and biological aspects for broad biomedical engineering applications. In this review, we introduce the basic multi-head bioprinters, semi-hybrid and fully-hybrid biomanufacturing systems, highlighting the modifications, the improved properties and the effect on the complex tissue regeneration applications.

Honey: An Advanced Antimicrobial and Wound Healing Biomaterial for Tissue Engineering Applications.

Honey was used in traditional medicine to treat wounds until the advent of modern medicine. The rising global antibiotic resistance has forced the development of novel therapies as alternatives to combat infections. Consequently, honey is experiencing a resurgence in evaluation for antimicrobial and wound healing applications. A range of both Gram-positive and Gram-negative bacteria, including antibiotic-resistant strains and biofilms, are inhibited by honey. Furthermore, susceptibility to antibiotics can be restored when used synergistically with honey. Honey's antimicrobial activity also includes antifungal and antiviral properties, and in most varieties of honey, its activity is attributed to the enzymatic generation of hydrogen peroxide, a reactive oxygen species. Non-peroxide factors include low water activity, acidity, phenolic content, defensin-1, and methylglyoxal (Leptospermum honeys). Honey has also been widely explored as a tissue-regenerative agent. It can contribute to all stages of wound healing, and thus has been used in direct application and in dressings. The difficulty of the sustained delivery of honey's active ingredients to the wound site has driven the development of tissue engineering approaches (e.g., electrospinning and hydrogels). This review presents the most in-depth and up-to-date comprehensive overview of honey's antimicrobial and wound healing properties, commercial and medical uses, and its growing experimental use in tissue-engineered scaffolds.

Preliminary Characterization of a Polycaprolactone-SurgihoneyRO Electrospun Mesh for Skin Tissue Engineering.

Skin is a hierarchical and multi-cellular organ exposed to the external environment with a key protective and regulatory role. Wounds caused by disease and trauma can lead to a loss of function, which can be debilitating and even cause death. Accelerating the natural skin healing process and minimizing the risk of infection is a clinical challenge. Electrospinning is a key technology in the development of wound dressings and skin substitutes as it enables extracellular matrix-mimicking fibrous structures and delivery of bioactive materials. Honey is a promising biomaterial for use in skin tissue engineering applications and has antimicrobial properties and potential tissue regenerative properties. This preliminary study investigates a solution electrospun composite nanofibrous mesh based on polycaprolactone and a medical grade honey, SurgihoneyRO. The processing conditions were optimized and assessed by scanning electron microscopy to fabricate meshes with uniform fiber diameters and minimal presence of beads. The chemistry of the composite meshes was examined using Fourier transform infrared spectroscopy and X-ray photon spectroscopy showing incorporation of honey into the polymer matrix. Meshes incorporating honey had lower mechanical properties due to lower polymer content but were more hydrophilic, resulting in an increase in swelling and an accelerated degradation profile. The biocompatibility of the meshes was assessed using human dermal fibroblasts and adipose-derived stem cells, which showed comparable or higher cell metabolic activity and viability for SurgihoneyRO-containing meshes compared to polycaprolactone only meshes. The meshes showed no antibacterial properties in a disk diffusion test due to a lack of hydrogen peroxide production and release. The developed polycaprolactone-honey nanofibrous meshes have potential for use in skin applications.

Three-Dimensional Printing and Electrospinning Dual-Scale Polycaprolactone Scaffolds with Low-Density and Oriented Fibers to Promote Cell Alignment.

Complex and hierarchically functionalized scaffolds composed of micro- and nanoscale structures are a key goal in tissue engineering. The combination of three-dimensional (3D) printing and electrospinning enables the fabrication of these multiscale structures. This study presents a polycaprolactone 3D-printed and electrospun scaffold with multiple mesh layers and fiber densities. The results show successful fabrication of a dual-scale scaffold with the 3D-printed scaffold acting as a gap collector with the printed microfibers as the electrodes and the pores a series of insulating gaps resulting in aligned nanofibers. The electrospun fibers are highly aligned perpendicular to the direction of the printed fiber and form aligned meshes within the pores of the scaffold. Mechanical testing showed no significant difference between the number of mesh layers whereas the hydrophobicity of the scaffold increased with increasing fiber density. Biological results indicate that increasing the number of mesh layers improves cell proliferation, migration, and adhesion. The aligned nanofibers within the microscale pores allowed enhanced cell bridging and cell alignment that was not observed in the 3D-printed only scaffold. These results demonstrate a facile method of incorporating low-density and aligned fibers within a 3D-printed scaffold that is a promising development in multiscale hierarchical scaffolds where alignment of cells can be desirable.