**5. Future outlook**

*Biomimetics*

**4.2 Wound dressing and wearable devices**

The bio-inspired hydrogels via 3D bioprinting can be applied for wound dressing and wearable devices, which are considered as important applications, especially in recent years. Skin plays an essential role in protecting the body from external damages, such as abrasions, lacerations, and burns, and so on. The full-thickness defects of the dermis layers are the most challenging wounds to heal because of the limitation of self-repairing capability; thus, the skin regeneration of skin with skin appendages still remains a tough challenge [72]. 3D bioprinting is being applied to fabricate skin constructs using biomaterial scaffolds with or without cells, to address the need for skin tissues suitable for transplantation for wound healing therapy. The natural polymers, including cellulose, collagen and chitin, alginate, and hyaluronic acids are employed to synthesis skin constructs due to the favorable biocompatibility, biodegradation, low-toxicity or nontoxicity, high moisture content, high availability and mechanical stability [73]. Feifei et al. fabricated gelatin methacrylate (GelMA) based bioink to print functional living skin using DLP-based 3D printing (**Figure 2**), while the printed skin could promote skin regeneration and neovascularization via mimicking the physiological structure of natural skin [52]. Furthermore, the bio-inspired hydrogels could not only be functionalized on skin regeneration but also as medical wearable devices. The conductive hydrogels could be designed and fabricated to acquire electronic devices with conductive, capacitive, switching properties, image displaying, and motion sensing [74]. Meihong et al. developed conductive, healable, and self-adhesive hybrid network hydrogels based on conductive functionalized single-wall carbon nanotube (FSWCNT), PVA and polydopamine. The prepared hydrogel exhibits fast selfhealing ability around 2 s, high self-healing efficiency of about 99%, and robust adhesiveness, which could be used for healable, adhesive, and soft human-motion sensors [75]. Zijian et al. synthesized a stretchable, self-healing and conductive hydrogel based on gelatin-enhanced hydrophobic association poly(acrylamide-*co*dopamine) with lithium chloride via physical crosslinking including hydrogen bonding, hydrophobic association, and complexation effect. The hydrogels displayed the stretchability of 1150%, tensile strength of 112 kPa, flexibility and puncture resistance. Also, the hydrogels possess extraordinary conductive property and stable changes in resistance signals [76]. Furthermore, the organogel-hydrogel hybrids have been limelight due to that such kind of hybrids could mimic biological organisms with exceptional freezing tolerance, and thus could provide an advantageous skill to fabricate robust ionic skins [77]. Zhixing developed a series of lauryl acrylate-based polymeric organogels with high transparency, mechanical adaptability, adhesive capability, and self-healing properties; the prepared organogels were expected to provide insights to design the artificial human-like skins with unprecedented functionalities [78]. Due to the delicate structure can be accomplished using 3D bioprinting, bio-inspired hydrogel shows potential applications in medical

The bio-inspired hydrogels could also be used in drug delivery system, such as protein carriers, anti-inflammatory drug carriers, in the pharmaceutical industry [79]. Rana et al. designed a magnetic natural hydrogel based on alginate, gelatin, and iron oxide magnetic nanoparticles as an efficient drug delivery system, the drug doxorubicin hydrochloride (DOX) was loaded, the anticancer activity against Hela cells could be regulated by the release of DOX from hydrogels [80]. Maling et al. provided a proof-of-concept of detoxification using a 3D-printed biomimetic

**10**

wearable devices.

**4.3 Pharmaceutical applications**

The design paradigms shift from 2D to 3D has revolutionized the way of bioinspired hydrogels for materials components, engineered constructs, *in vitro* disease modeling, medical wearable devices, and precision medicine. 3D bioprinting technology realizes to fabricate the delicate bio-inspired hydrogels with excellent properties and necessary signals to promote healing, tissue regeneration, therapeutics delivery, and health monitor in real-time. However, there are still some issues that need to be addressed in the near future (**Figure 4**). As the researchers begin to scale-up the production of bio-inspired hydrogels, new parameters during the fabrication need be met, such as the bioprinting speeds and resolutions, such parameters need to be simultaneously be increased to create constructs of clinic size. In the near future, it will be essential to develop microscale organ-on-a-chip, such as liver- and heart-on-a-chip, tumor-on-a-chip, etc., that integrate bioinspired microenvironments with fluid flow inside hydrogels, also other dynamic physiological processes were well regulated by controlling the 3D bioprinting process. For example, the bio-inspired 3D culture in hydrogels could be employed to produce an *in vitro* model of Alzheimer's disease, providing a useful tool for the development of new therapeutics [82]. Future fabrication of bio-inspired hydrogels would be involved with multi-material 3D bioprinting, which provides the ability

to deliver growth factors, control cell adhesion, as well as the degradation rate in different regions of the printed constructs. In addition, 3D bioprinting technology needs to overcome vascularization challenge, which is considered a crucial factor in the synthesis of engineered constructs in tissue engineering.
