# Advances in Three Dimensional Bioprinting for Wound Healing: A Comprehensive Review
## 3 Overview of Wound Pathophysiology and Wound Healing Process
### 3D Bioprinted Wound Dressings  
Traditional wound dressings physically protect the wound and absorb exudate. Modern wound dressings created with 3D bioprinters offer additional contributions to wound healing compared to traditional ones [16]. Optimum wound dressings should provide the ideal temperature and a moist environment for the wound, increase epidermal migration, angiogenesis and connective tissue synthesis, allow gas exchange, protect against bacteria, provide ideal adhesion to the wound, enhance the debridement effect and sweep enzyme accumulation, and be biocompatible [8]. For these features, it is possible to print composite wound dressings with a 3D bioprinting method. Several studies have examined the efficacy of different types of bioinks (including natural, synthetic, or composite materials) for restoring skin integrity and accelerating wound healing. Among them, hydrogel-based bioinks dominate the field of 3D-bioprinted wound dressings due to their similarities to natural tissues (Figure 1C). A 3D hydrophilic polymer network of hydrogel composed of homopolymers, or copolymers, gives these materials significant swelling properties, while also making them insoluble in water [51]. Their water content may vary from 10-20% [52] up to several thousand times of their dry weight. Even though hydrogels present similar characteristics to other polymers in their dry state, they differ from other polymers once swollen. Hydrogels have both solid-like structural integrity and fluid-like diffusion transport properties, which makes them act as a natural tissue and enhances their biocompatibility in the swollen state [53]. Furthermore, chemical and/or physical linkages between individual polymer chains determine the structural integrity of hydrogels and their characteristic responses to various external stimuli, such as changes in pH, temperature, salt concentration, exposure to light, electromagnetic fields, and biomolecules [54; 55]. Several techniques are available to produce hydrogel-based wound dressings, including wet chemistry; mechanical rupture, incorporating trypsin/EDTA processes or hypertonic/hypotonic solutions; electrospinning, and 3D bioprinting [56; 57; 58; 59; 60; 61; 62; 63]. Wet chemistry involves cross-linking polymer chains in a solution to form a hydrogel, whereas mechanical rupture involves breaking apart preformed hydrogels. Hypertonic and hypotonic solutions may be used to induce hydrogel swelling or shrinkage. The trypsin/EDTA process creates porous structures by using enzymes to treat hydrogels. Electrospinning is an electrohydrodynamic process controlled by viscosity, and involves creating ultrafine fibers from a polymer solution, which can also be assembled into a hydrogel dressing production. As a different method, 3D bioprinting uses a computer-controlled printing process to produce a hydrogel structure with the desired shape and properties. These techniques offer a range of options for producing hydrogel-based wound dressings with different properties and functions. Hydrogels can absorb from 10% to thousands of times their weight in water. As a result, they maintain the wound's moisture, contribute to the removal of necrotic tissue, and are transparent. Moreover, their degradation time can be adjusted for controlling drug delivery. Based on these characteristics, they are recommended for pressure ulcers, surgical wounds, burns, radiation dermatitis, and wounds with low to moderate exudate levels [50]. Hydrogel wound dressings have low mechanical strength due to their high water retention capacity, which might necessitate a second wound covering. Additionally, their liquid retention capability can promote bacterial growth. To mitigate this, a composite structure is formed with antimicrobial agents. In cases of injuries related to illnesses causing a weakened immune system, active antimicrobial pharmaceuticals are typically employed, while ensuring this does not disrupt the wound environment [64].