Background The requirements for cell-encapsulated injectable and bioprintable hydrogels are extrusion ability, cell supportive micro-environment and reasonable post-printing stability for the acclimatization of the cells in the target site. Detonation nanodiamond (ND) has shown its potential to improve the mechanical and biological properties of such hydrogels. Enhancing the performance properties of natural biopolymer gelatin-based hydrogels can widen their biomedical application possibilities to various areas including drug delivery, tissue engineering and 3D bioprinting. Method In this study, natural cross-linker tannic acid (TA) is used along with ferrous sulphate (FS) to optimize the swelling and disintegration of extrudable and 3D printable gelatin hydrogels. The amounts of TA and FS are restricted to improve the extrusion ability of the gels in 3D printing. Further, ND particles (detonation type) are dispersed using twin screw extrusion technology to study their effect on mechanical and biological properties of the 3D printing hydrogel. Results The improved dispersion of ND particles helps to improve compressive strength almost ten times and dynamic modulus three times using 40 mg ND (2% w/w of gelatin). The surface-functional groups of detonation ND also contributed for such improvement in mechanical properties due to higher interaction with the hydrogel matrix. The stability of the hydrogels in water was also improved to 7 days. Four times improvement of the cell growth and proliferation was observed in ND based hydrogel. Conclusion The cell-supportive nature of these moderately stable and extrudable ND dispersed gelatin hydrogels makes them a good candidate for short term regenerative applications of cell-encapsulated injectable hydrogels with better mechanical properties.

Efficient incorporation of high molecular weight drug into prefabricated hydrogel and its delivery are big challenges in its applications to drug delivery and tissue regeneration using a 3D bioprinting system. In this work, a new method of loading a model high molecular weight drug (fucoidan with 200 kDa) into prefabricated hyaluronate‐based terpolymeric gel is developed by using an advanced screw‐based extrusion printing system. This system effectively incorporates the fucoidan biomolecules into the prefabricated crosslinked gel within 60 s at significantly higher percentages without much change in gel properties. Less damage in gel network is achieved through variable pitch and differential extensional shear mechanism by optimization of bioprinting conditions. Importantly, fucoidan‐loaded nanoparticles (NPs) are developed using the advanced extrusion system at high screw rpm and with increased residence time using recirculation. The encapsulation efficiency, sustained release of fucoidan, and in vitro cell culture studies confirm the nontoxic nature of the drug‐loaded gels and nanogels at lower doses, exhibiting the biomedical application potentials of this advanced screw‐based extrusion printing system and drug‐loaded NPs formation in pharmaceuticals, 3D bioprinting, tissue engineering as well as maximal drug loading into and sustained release from prefabricated gels.