Aqueous solutions of some amphiphilic block copolymers undergo a sol-gel transition upon heating and are thus called thermogels. In the thermogel family, some systems also exhibit a gel-sol (suspension) transition at higher temperatures following the sol-gel transition, which is usually ignored in biomedical applications. Herein, for the first time, a case is reported employing both the sol-gel transition and the gel-sol (suspension) transition, which is found in the development of a transdermal hydrogel formulation containing 5-aminolevulinic acid for photodynamic therapy (PDT) of skin disease. Two poly(d,l-lactide-co-glycolide)-b-poly(ethylene glycol)-b-poly(d,l-lactide-coglycolide) triblock copolymers of different block lengths are synthesized. The transition temperatures of the formulation can be easily adjusted to meet the condition of sol-gel transition temperature (T gel ) < room temperature (T air ) < gel-sol (suspension) temperature (T sol (suspension) ) < body temperature (T body ) via changing the blending ratio. Therefore, after applying to skin, formulation of spontaneous asymmetry with a hydrogel outside and a sol (suspension) inside can avoid free flowing and achieve rapid release to ensure an efficient PDT. This study demonstrates such a concept via characterizations of the "block blend" biomaterials and drug release profiles, and also via cell experiments, in vitro permeation, and in vivo transdermal delivery studies.

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Main observation and conclusion Ring‐opening polymerization (ROP) of cyclic esters in the presence of stannous octoate (Sn(Oct)2) is the main way to obtain biodegradable aliphatic polyesters, an important family of biodegradable polymers which have been widely used and still rapidly developed in the fields of biomedical polymers and environment‐friendly materials. The underlying mechanism is thought via a coordination‐insertion way, but the pathway is still open owing to the absence of direct experimental evidence. Herein, we inquire this issue through density functional theory (DFT) calculations. According to our DFT calculations and the following Curtin‐Hammett evaluation, the carbonyl oxygen has a significant advantage over the ester oxygen, and thus the ring is opened mainly through pathway A instead of pathway B. The stannous octoate is identified as a catalyst rather than an initiator. We eventually summarize the main stages during the whole polymerization of lactide.

Traditional skin care masks usually use a piece of paper to hold the aqueous essences, which are not environmentally friendly and not easy to use. While a paper-free mask is desired, it is faced with a dilemma of moisture holding and rapid release of encapsulated bioactive substances. Herein, a paper-free sprayable skin mask is designed from an intelligent material-a thermogel which undergoes sol-gel-suspension transitions upon heating-to solve this dilemma. A synthesized block copolymer of poly(ethylene glycol) and poly(lactide-co-glycolide) with appropriate ratios can be dissolved in water, and thus easily mixed with a biological substance. The mixture is sprayable. After spraying, a Janus film is formed in situ with a physical gel on the outside and a suspension on the inside facing skin. Thus, both moisture holding and rapid release are achieved. Such a thermogel composed of biodegradable amphiphilic block copolymers loaded with nicotinamide as a skin mask is verified to reduce pigmentation on a 3D pigmented reconstructed epidermis model and further in a clinical study. This work might be stimulating for investigations and applications of biodegradable and intelligent soft matter in the fields of drug delivery and regenerative medicine.

Although surgical resection is currently the first choice of clinical treatment for most solid tumors, postoperative cancer recurrence and metastasis are the main causes of mortality. Herein, the authors aim to enable immunotherapy consistent with surgery. To this end, the term “therapeutic‐prophylactic vaccine (TPV)” is suggested, and a TPV‐gel is developed as a filler after resection of ≈90% tumor to eradicate residue tumor (therapeutic) and prevent recurrence and metastasis (prophylactic). The TPV‐gel is made of the matrix of blends of two poly(d,l‐lactide‐co‐glycolide)‐b‐poly(ethylene glycol)‐b‐poly(d,l‐lactide‐co‐glycolide) block copolymers and the bioactive substances of inorganic calcium salt and organic R837. The aqueous system of polymeric block blends undergoes a sol‐gel transition upon heating and thus leads to an injectable hydrogel filling the resection site; loading of CaCl2 and CaCO3 results in the release of calcium ions out of the TPV‐gel, which induces immunogenic cell death of the residual tumor cells; R837, an immune adjuvant, is dispersed in the TPV‐gel as microcrystal and can be released to awaken immune responses. The therapeutic and prophylactic efficacy of this TPV‐gel is confirmed in vitro and in vivo using a postoperative breast 4T1 mice model.