Natural polymers have been widely used for biomedical applications in recent decades. They offer the advantages of resembling the extracellular matrix of native tissues and retaining biochemical cues and properties necessary to enhance their biocompatibility, so they usually improve the cellular attachment and behavior and avoid immunological reactions. Moreover, they offer a rapid degradability through natural enzymatic or chemical processes. However, natural polymers present poor mechanical strength, which frequently makes the manipulation processes difficult. Recent advances in biofabrication, 3D printing, microfluidics, and cell-electrospinning allow the manufacturing of complex natural polymer matrixes with biophysical and structural properties similar to those of the extracellular matrix. In addition, these techniques offer the possibility of incorporating different cell lines into the fabrication process, a revolutionary strategy broadly explored in recent years to produce cell-laden scaffolds that can better mimic the properties of functional tissues. In this review, the use of 3D printing, microfluidics, and electrospinning approaches has been extensively investigated for the biofabrication of naturally derived polymer scaffolds with encapsulated cells intended for biomedical applications (e.g., cell therapies, bone and dental grafts, cardiovascular or musculoskeletal tissue regeneration, and wound healing).

Hydrogel-based bio-inks have recently attracted more attention for 3D printing applications in tissue engineering due to their remarkable intrinsic properties, such as a cell supporting environment. However, their usually weak mechanical properties lead to poor printability and low stability of the obtained structures. To obtain good shape fidelity, current approaches based on extrusion printing use high viscosity solutions, which can compromise cell viability. This paper presents a novel bio-printing methodology based on a dual-syringe system with a static mixing tool that allows in situ crosslinking of a two-component hydrogel-based ink in the presence of living cells. The reactive hydrogel system consists of carboxymethyl chitosan (CMCh) and partially oxidized hyaluronic acid (HAox) that undergo fast self-covalent crosslinking via Schiff base formation. This new approach allows us to use low viscosity solutions since in situ gelation provides the appropriate structural integrity to maintain the printed shape. The proposed bio-ink formulation was optimized to match crosslinking kinetics with the printing process and multi-layered 3D bio-printed scaffolds were successfully obtained. Printed scaffolds showed moderate swelling, good biocompatibility with embedded cells, and were mechanically stable after 14 days of the cell culture. We envision that this straightforward, powerful, and generalizable printing approach can be used for a wide range of materials, growth factors, or cell types, to be employed for soft tissue regeneration.

The effective treatment of chronic wounds constitutes one of the most common worldwide healthcare problem due to the presence of high levels of proteases, free radicals and exudates in the wound, which constantly activate the inflammatory system, avoiding tissue regeneration. In this study, we describe a multifunctional bioactive and resorbable membrane with in-built antioxidant agent catechol for the continuous quenching of free radicals as well as to control inflammatory response, helping to promote the wound-healing process. This natural polyphenol (catechol) is the key molecule responsible for the mechanism of adhesion of mussels providing also the functionalized polymer with bioadhesion in the moist environment of the human body. To reach that goal, synthesized statistical copolymers of N-vinylcaprolactam (V) and 2-hydroxyethyl methacrylate (H) have been conjugated with catechol bearing hydrocaffeic acid (HCA) molecules with high yields. The system has demonstrated good biocompatibility, a sustained antioxidant response, an anti-inflammatory effect, an ultraviolet (UV) screen, and bioadhesion to porcine skin, all of these been key features in the wound-healing process. Therefore, these novel mussel-inspired materials have an enormous potential for application and can act very positively, favoring and promoting the healing effect in chronic wounds.

The effective treatment for chronic wounds constitute one of the most common worldwide health care problem due to the presence of high levels of proteases, free radicals and exudates in the wound, which constantly activate the inflammatory system avoiding the tissue regeneration. In this study, we describe a multifunctional bioactive and resorbable membrane with in-built antioxidant agent for the continuous quenching of free radicals as well as to control inflammatory response helping to promote the wound healing process. To reach that goal synthesized statistical copolymers of N-vinylcaprolactam (V) and 2-hydroxyethyl methacrylate (H) have been conjugated with catechol bearing hydrocaffeic acid (HCA) molecules. The natural polyphenol (catechol) is the key molecule responsible for the mechanism of adhesion of mussels, and provides the functionalized polymer conjugate a continuous antioxidant response, antiinflammatory effect, UV screen and bioadhesion in the moist environment of the human body, all of them key features in the wound healing process. Therefore, these novel mussel-inspired materials have an enormous potential of application and can act very positively, favoring and promoting the healing effect in chronic wounds.