Chronic wounds caused by diabetic or venous diseases remain a social and healthcare burden. In this work, a new strategy is proposed in which injectable thermosensitive chitosan/collagen/β-glycerophosphate (β-GP) hydrogels were combined with three-dimensional mesenchymal stem cell (3D MSC) spheroids to accelerate chronic wound healing by enhanced vascularization and paracrine effects. Chitosan/collagen/β-GP solution mixed with 3D MSC spheroids was rapidly transformed to a gel at body temperature by physical cross-linking, then overlapped the wounds fully and fitted to any shape of the wound. The results showed that the combination therapy exhibited a markedly therapeutic effect than the hydrogel-loaded two-dimensional (2D) MSCs or 2D MSCs alone. The hydrogel could provide an environment conductive to the attachment and proliferation of encapsulated MSCs, especially accelerating the proliferation and paracrine factor secretion of 3D MSC spheroids. These results supplied a novel alternative approach to treat chronic wounds caused by diabetic or venous diseases.

In comparison with the implantable electronics, ingestible electronics are less invasive but can travel close to major organs through the gastrointestinal (GI) tract, monitor a wide range of biomarkers and therapeutic targets, and serve as effective clinical tools for diagnostics and therapy. [4d,5] Today, GI conditions have become one of the most prevalent health concerns in modern society. The market was expected to nearly reach the one-billion-dollar mark. [4e] Through analyzing the conditions of the GI tract [4d] (Figure 1), many diseases can be monitored and diagnosed, e.g., refluxing gastric fluid, cancer, motility disorders, infected and abnormally dilated venous vessels, gastritis, gastric ulcers, coeliac disease, lactose intolerance, Crohn's disease, inflammatory bowel disease, diverticular disease, constipation, clostridium difficile-associated diarrhea, irritable bowel syndrome, etc. [5,6] Conventional ingestible electronics mostly consist of inorganic materials and encapsulated with rigid nondegradable polymer, such as polydimethylsiloxane, parylene/epoxy, [4a] which will lead longer devices retention in the GI tract. This is one of the most significant risk elements during the application of conventional ingestible electronics. Fully food-based edible and nutritive electronics have emerged to address these potential risks. Edible electronics are new generation ingestible electronics. Recently, there is no accurate and clear definition of edible electronics. [4g,7] The definition of "transient electronics," [3h] which focused on implantable electronics, was similar to the edible electronics concept and defined as: made of biodegradable materials and can completely or partially dissolve, resorb, or physically disappear after functioning in environmental or physiological conditions at controlled rates. By follow this spirit, the definition of edible electronics is provided here: a class of microencapsulated electronic devices that consist of edible and nutritive inorganics and organics materials, meanwhile, that can be mainly dissolved, digested and absorbed after fulfilling the diagnosis or therapy of diseases in the gastrointestinal tract. The edible and nutritive inorganics always include edible inert metals, trace elements [8] and their oxides. Nutritive organics always include biopigments, and polymers. [7,9] A more systemic and expanded materials toolbox will be very helpful to advance The emerging novel edible and nutritive electronics indicate an important advance in ingestible and implantable electronics, covering multiple disciplines such as biomedicine, electronics, and nutriology. This review focuses on the feasibility and critical technical problems of fabricating fully edible and nutritive electronics. Recently, a limited number of fully edible and nutritive electronics, operating single functions, have been applied to monitor the condition of the gastrointestinal (GI) tract and diagnose its disorders. However, fully edible, nutritive, miniaturized, and well-functioning electronics with mu...