The engineering of human tissues to cure diseases is an interdisciplinary and a very attractive field of research both in academia and the biotechnology industrial sector. Three-dimensional (3D) biomaterial scaffolds can play a critical role in the development of new tissue morphogenesis via interacting with human cells. Although simple polymeric biomaterials can provide mechanical and physical properties required for tissue development, insufficient biomimetic property and lack of interactions with human progenitor cells remain problematic for the promotion of functional tissue formation. Therefore, the developments of advanced functional biomaterials that respond to stimulus could be the next choice to generate smart 3D biomimetic scaffolds, actively interacting with human stem cells and progenitors along with structural integrity to form functional tissue within a short period. To date, smart biomaterials are designed to interact with biological systems for a wide range of biomedical applications, from the delivery of bioactive molecules and cell adhesion mediators to cellular functioning for the engineering of functional tissues to treat diseases.

Fabrication of biomaterials scaffolds using various methods and techniques is discussed, utilising biocompatible, biodegradable and stimuli-responsive polymers and their composites. This review covers the lithography and printing techniques, self-organisation and self-assembly methods for 3D structural scaffolds generation, and smart hydrogels, for tissue regeneration and medical devices.

A library of block copolymers was synthesized by varying the molecular weight of the poly(ε-caprolactone) (PCL)-diol soft segment (M_w = 850, 3050, 3700 or 7000), which was reacted with methylene diphenyl diisocyanate (MDI), 1,4-phenylene diisocyanate (PDI), 1,1′-methylenebis(4-isocyanatocyclohexane) (HMDI), or 2,4-toluene diisocyanate (TDI) with 1,4-butanediol (BD) or ethylene glycol (EG) added as chain extenders. Thermal and X-ray measurements indicated that the crystalline structure of the copolymers was largely dependent on the chain length of the PCL-diol, with no crystallization taking place with the smallest diol (M_w = 850) using MDI, TDI or HMDI. However, the copolymers produced from a PCL-diol (M_w = 850) and PDI and chain extenders (BD or EG) showed resolved crystalline peaks while no peaks appeared with other diisocyanates. Hydrolytic degradation studies demonstrated a faster degradation rate in the case of more amorphous copolymers than semi-crystalline copolymers. The cellular compatibility of the copolymers was evaluated by fabricating the entire library of polymers in a microarray format and in vitro cell culture, demonstrating that all the 57 copolymers supported cellular attachment and growth.

Molecular interactions of amino functional (AF) monomers with chitosan (CS) lead to the formation of external stimuli responsive hydrogels (HGs). These have the potential to produce biomaterials with novel properties by a simple blending approach. Six independent AF monomers such as diethylenetriamine (DETA), bis(3-aminopropyl)amine (BAPA), 3,3′-diamino-N-methyldipropyleamine (DAMPA), hexamethylenediamine (HMDA), N,N-dimethylethylamine (DMEA) and diethylamine (DEA) with distinct functional groups and chain lengths were designed to form stable HGs at physiological pH. Such AF monomers are able to form HGs within a short time (in the range from 10 to 19 seconds) by physically interacting with CS. This is an alternative to the covalently crosslinking reaction process, providing cost effective HG biomaterials. HG complexes were characterized by rheometry, differential scanning calorimetry (DSC), and Fourier transform infrared (FTIR) spectroscopy. The interaction between AF monomers and the CS polymer has been discussed and the results have been confirmed by FTIR analysis. The storage modulus (G′), loss modulus (G′′) and complex viscosity (η*) were evaluated for all HGs using a rheometer, and the ratios of CS and the particular AF monomer were optimized for stable HG formation. The swelling ratio was evaluated using a simple method and was found to be directly related to the structure of the AF monomer, pH and temperature. These HGs were utilised for encapsulation, and the release of active molecules (e.g., reactive red 120 (RR120) as a model compound) was measured at low pH 5.5, physiological pH 7.4 and high pH 9.5. The cell viability and cellular compatibility of the HGs were evaluated in vitro cell culture, demonstrating that all the five different types of HGs support cellular compatibility, attachment and growth. The physical mixing of AF monomers with CS is expedited for the development of new bespoke economically viable biomaterials.