# Advances in Three Dimensional Bioprinting for Wound Healing: A Comprehensive Review
## 5 Recent Advances in Hydrogel-Based 3D Printing for Wound Healing
### Drug Delivery
(**C1**) Illustration for in vivo printing and photo-crosslinking of GelMA precursor enriched with VEGF. (**C2**) Photograph of portable printers and their components. (**C3**) Photograph of hydrogel scaffold printed during the process, flow rate versus percentage of maximum speed range and diameter versus printing speed of bioink graph of resultant material. (**C4**) SEM images of hydrogel scaffold. Then, highly complex structures consisting of two-layer 3D-bioprinted hydrogel-based dressing were proposed for the treatment of diabetic wounds [251]. The first layer formed from the 3D bioprinting strip of 2-(acryloyloxy) ethyl Trimethylammonium chloride (Bio-IL) and GelMA. The second layer was 3D-printed on a doxycycline hydrochloride-loaded (DOXH) and ROS-degradable polyurethane nanofibrous membrane. UV irradiation was applied to final dressings to activate immunomodulation and electroconductivity features. The dressing promoted the migration of endothelial cells and the polarization of macrophages to the anti-inflammatory phenotype (M2) in vitro. Rats were injected with streptozotocin to induce diabetes, and then full-thickness wounds were created on their bodies. Then, the scaffolds were applied to the wounds to assess their efficacy in promoting in vivo wound healing. As a result of this test, the combination of conductivity and DOXH was most effective in accelerating wound healing, collagen deposition, revascularization, and re-epithelialization. This combination reduced ROS and inflammatory factor levels and increased the ratio of M2 macrophages. To prevent melanoma recurrence after surgical operation, a hybrid hydrogel scaffold with a mixture of sodium ALG, gellan gum and polydopamine NPs was manufactured. The printed hybrid hydrogel scaffold displayed good mechanical strength and biocompatibility. Polydopamine NPs provided a decent photothermal effect to the scaffold. They can also provide photothermal chemotherapy by coating it with a heat-sensitive gelatin hydrogel loaded with doxorubicin. Consequently, this method can accelerate drug release, suppress tumor cell proliferation, and recurrence after surgical resection. Due to the porous structure of the hydrogel scaffolds, HUVEC can increase proliferation and migration as well as tissue growth. Thus, it supports post-operative wound healing [252]. To inhibit the irregular remodeling of ECM that causes scar tissue to form in the wound healing process, another team prepared a polyvinylidene fluoride/sodium ALG piezoelectric hydrogel scaffold involving modified zinc oxide NPs with 3D printing technology [253]. The scaffold has dual piezoelectric response patterns, mainly comprising vertical swelling and horizontal friction. It can be used to simulate and amplify endogenous bioelectricity to promote wound healing and prevent wound formation. Ultimately, the proposed dual piezoelectric response models provided a novel solution to accelerate the wound healing process, prevent scarring, and expand the application of piezoelectric materials in wound dressings. Recently, [PERSON] et al. examined active dressing: a hydrogel-based 3D printing dressing consisting of CH/ALG for wound healing [77]. A freeze deposition 3D printing method was used to fabricate CH/ALG hydrogels with modifiable thickness and interconnected pore structures. The printed hydrogels were further crosslinked to enhance their mechanical properties and stability. The ALG hydrogels were loaded with 0.75% \(w/v\) silver sulfadiazine (SSD), a drug model typically used for the treatment of infected burn wounds. Four alternative 3D CH/ALG structures were constructed to regulate the release of the indicated active molecule. The water content, flexibility, and porosity of the CH/ALG structures were remarkable. The Young's modulus of ALG and CH hydrogels was 0.582 \(\pm\) 0.019 MPa and 0.365 \(\pm\) 0.015 MPa, respectively. The water content in ALG was 93.18% and 0.88%, while the water content in CH was 92.76% and 1.17%.