Melanins are a group of dark insoluble pigments found widespread in nature. In mammals, the brown-black eumelanins and the reddish-yellow pheomelanins are the main determinants of skin, hair, and eye pigmentation and play a significant role in photoprotection as well as in many biological functions ensuring homeostasis. Due to their broad-spectrum light absorption, radical scavenging, electric conductivity, and paramagnetic behavior, eumelanins are widely studied in the biomedical field. The continuing advancements in the development of biomimetic design strategies offer novel opportunities toward specifically engineered multifunctional biomaterials for regenerative medicine. Melanin and melanin-like coatings have been shown to increase cell attachment and proliferation on different substrates and to promote and ameliorate skin, bone, and nerve defect healing in several in vivo models. Herein, the state of the art and future perspectives of melanins as promising bioinspired platforms for natural regeneration processes are highlighted and discussed.

1,8-Naphthalenediol (dihydroxynaphthalene, 1,8-DHN) has been shown to be a potent hydrogen atom transfer (HAT) antioxidant compound because of the strong stabilization of the resulting free radical by intramolecular hydrogen bonding. However, the properties, reactivity, and fate of the 1,8-DHN phenoxyl radical have remained so far uncharted. Herein, we report an integrated experimental and computational characterization of the early intermediates and dimer products that arise by the oxidation of 1,8-DHN. Laser flash photolysis (LFP) studies of HAT from 1,8-DHN to the cumyloxyl and aminoxyl radicals showed the generation of a transient species absorbing at 350, 400, and >600 nm attributable to the 1,8-DHN phenoxyl radical. Peroxidase/H₂O₂ oxidation of 1,8-DHN was found to proceed via an intense blue intermediate (λ_max 654 nm) preceding precipitation of a black melanin-like polymer. By halting the reaction in the early stages, three main dimers featuring 2,2′-, 2,4′-, and 4,4′-bondings could be isolated and characterized in pure form. Density functional theory calculations supported the generation of the 1,8-DHN phenoxyl radical and its subsequent coupling via the 2- and 4-positions giving extended quinone dimers with intense transitions in the visible range, consistent with UV–vis and LFP data. Overall, these results allowed to elucidate the mechanism of oxidative polymerization of 1,8-DHN of possible relevance to melanogenesis in fungi and other processes of environmental and astrochemical relevance.

Gellan gum (GG) was chemically modified with methacrylic moieties to produce a photocrosslinkable biomaterial ink, hereinafter called methacrylated GG (GGMA), with improved physico-chemical properties, mechanical behavior and stability under physiological conditions. Afterwards, GGMA was functionalized by incorporating two different bioactive compounds, a naturally derived eumelanin extracted from the black soldier fly (BSF-Eumel), or hydroxyapatite nanoparticles (HAp), synthesized by the sol–gel method. Different ink formulations based on GGMA (2 and 4% (w/v)), BSF-Eumel, at a selected concentration (0.3125 mg/mL), or HAp (10 and 30% w_HAp/w_GGMA) were developed and processed by three-dimensional (3D) printing. All the functionalized GGMA-based ink formulations allowed obtaining 3D-printed GGMA-based scaffolds with a well-organized structure. For both bioactive signals, the scaffolds with the highest GGMA concentration (4% (w/v)) and the highest percentage of infill (45%) showed the best performances in terms of morphological and mechanical properties. Indeed, these scaffolds showed a good structural integrity over 28 days. Given the presence of negatively charged groups along the eumelanin backbone, scaffolds consisting of GGMA/BSF-Eumel demonstrated a higher stability. From a mechanical point of view, GGMA/BSF-Eumel scaffolds exhibited values of storage modulus similar to those of GGMA ones, while the inclusion of HAp at 30% (w_HAp/w_GGMA) led to a storage modulus of 32.5 kPa, 3.5-fold greater than neat GGMA. In vitro studies proved the capability of the bioactivated 3D-printed scaffolds to support 7F2 osteoblast cell growth and differentiation. BSF-Eumel and HAp triggered a different time-dependent physiological response in the osteoblasts. Specifically, while the ink with BSF-Eumel acted as a stimulus towards cell proliferation, reaching the highest value at 14 days, a higher expression of alkaline phosphatase activity was detected for scaffolds consisting of GGMA and HAp. The overall findings demonstrated the possible use of these biomaterial inks for 3D-printed bone tissue-engineered scaffolds.