# Advances in Three Dimensional Bioprinting for Wound Healing: A Comprehensive Review
## 5 Recent Advances in Hydrogel-Based 3D Printing for Wound Healing  
### Drug Delivery  
In recent years, 3D printing has attracted significant attention to drug delivery research because of its capability to produce highly customized products in an efficient manner. Thanks to the customization options of bioinks, it is possible to load drugs into hydrogels during the printing process. For instance, HA and carboxymethylcellulose (CMC) were used to produce a highly elastic, biocompatible, and microporous hydrogel network that was capable of being printed in multiple layers without the need to add additional materials or post-printing processes [246]. This method rapidly self-crosslinks hydrogels in the 3D printing process and is capable of rapid self-healing without damaging the integrated cells. In vitro drug release and cell culture studies revealed that 3D-printed structures (pore size \(\cong\) 50 \(\upmu\)m) formed thicker networks caused by higher stress during the needle extrusion, displaying slower drug release from the printed gel until 96 h and Live/Dead ratios of 78 \(\pm\) 8, and 68 \(\pm\) 2 for 1 h to 24 h, respectively. In vivo studies were undertaken by placing hydrogels subcutaneously on mice. At 1 week after injection, the angiogenesis in the HA-CMC groups was 14.8 \(\pm\) 2.8, which was significantly higher than the control group (4.8 \(\pm\) 1.3). At 4 weeks after injection, the angiogenesis in the HA-CMC groups was 17.6 \(\pm\) 2.4, which was approximately 20% higher than the control group. The conducted in vivo studies revealed 80% infiltration of the surrounding tissues after one week, and all the hydrogel groups did not degrade after four weeks. For the treatment of impetigo, a common and highly contagious bacterial skin infection that mostly affects young children and infants, a new PF-127-CH hydrogel containing cephalexin NPs was developed as a topical antibacterial delivery system. By embedding polymeric NPs into the heat-sensitive hydrogel, the authors achieved improved tissue targeting, reduced burst release, and a controlled drug release rate. In this study, [PERSON] et al. used CH, known for its antibacterial and bioadhesive properties. The resulting heat-sensitive and bioadhesive cephalexin nanohydrogel shows great potential as a topical antibacterial delivery system that can not only reduce therapy costs, but also minimize antibiotic-associated adverse effects [247]. The controlled release of drugs is achievable using photo-responsive materials in drug delivery. 3D-printed hydrogel/PCL core/shell fiber scaffolds were produced to show NIR-triggered drug release for cancer therapy and wound healing. Gel/PCL/PDA scaffolds were prepared by firstly 3D-printing core scaffolds, then dipping them in PCL solution, and finally coating them with PDA. The 30% PCL-coated ALG-gelatin hydrogels had a tensile strength and Young's modulus of 253 \(\pm\) 51.1 KPa and 2.98 \(\pm\) 0.2 MPa, respectively. Compared to uncoated gel scaffolds, the PCL coating increased tensile strength and modulus by 4-6 times, although PDA (Polydopamine) coating did not alter mechanical properties since the scaffold thickness was only 50 nm. The 3D-printed Gel/PCL/PDA scaffolds showed a fast degradation rate, and only 15% of weight remained after 28 days of incubation. To assess drug release in vivo, doxorubicin-loaded scaffolds were placed hypodermically into the wound areas of mice. In vivo photothermal effect evaluation revealed that Gel/PCL/PDA scaffolds reached 55 \({}^{\circ}\)C after NIR laser irradiation (0.5 W/cm\({}^{2}\)) for 3 min, while the Gel/PCL scaffold reached 42 \({}^{\circ}\)C, confirming the good photothermal conversion capability of PDA coated scaffolds. In vivo drug release tests showed that Gel/PCL/PDA scaffolds' doxorubicin loading efficiency was 80.0 \(\pm\) 2.9%; most of the drugs were still preserved.