The aim of this research is to utilize a hybrid system of liposomal doxorubicin (DOX-Lip) loaded thermogel (DOX-Lip-Gel) to realize the steady sustained delivery of doxorubicin (DOX), a small hydrophilic drug, for the treatment of breast cancer locally. Herein, liposomal doxorubicin was prepared via the traditional film dispersion method with the particle size of 75 nm and drug entrapment efficiency of 86%. And, the triblock copolymer of poly (D, L-lactide-co-glycolide)-b-poly (ethylene glycol)-b-poly (D, L-lactide -co-glycolide) (PLGA-PEG-PLGA) was synthesized via ring-opening polymerization to prepare the thermosensitive hydrogel through dissolving the polymers in DOX-Lip solution. The liposome loaded hydrogel was in a sol state at room temperature and converted into the gel state at body temperature and would degrade gradually during the time in vivo. The drug release of DOX out of DOX-Lip-Gel could be in a steady sustained manner up to 11 days without significant burst release as compared to that of DOX-loaded hydrogel (DOX-Gel). An orthotopic breast cancer model was adopted to evaluate the in vivo antitumor efficacy. And, the results revealed DOX-Lip-Gel had better antitumor efficiency as well as lower side effects.

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.

Nowadays, biomaterials have evolved from the inert supports or functional substitutes, to the bioactive materials able to trigger or promote the regenerative potential of tissues. The interdisciplinary progress has broadened the definition of “biomaterials”, and a typical new insight is the concept of tissue induction biomaterials. The term “regenerative biomaterials” and thus the contents of the present paper are relevant to yet beyond tissue induction biomaterials. This review summarizes the recent progress of medical materials including metals, ceramics, hydrogels, other polymers, and bio-derived materials. As the application aspects are concerned, this paper introduces regenerative biomaterials for bone and cartilage regeneration, cardiovascular repair, three dimensional bioprinting, wound healing, and medical cosmetology. Cell-biomaterial interactions are highlighted. Since the global pandemic of COVID-19, the review particularly mentions biomaterials for public health emergency. In the last section, perspectives are suggested: (1) Creation of new materials is the source of innovation; (2) Modification of existing materials is an effective strategy for performance improvement; (3) Biomaterial degradation and tissue regeneration are required to be harmonious with each other; (4) Host responses can significantly influence the clinical outcomes; (5) The long-term outcomes should be paid more attention to; (6) The non-invasive approaches for monitoring in vivo dynamic evolution are required to be developed; (7) Public health emergencies call for more research & development of biomaterials; (8) Clinical translation needs to be pushed forward in a full-chain way. In the future, more new insights are expected to be shed into the brilliant field — regenerative biomaterials.

Reactive nitrogen species (RNS) generated via the reaction of nitric oxide (NO) with reactive oxygen species (ROS) are more lethal than ROS, and thus RNS‐mediated therapy has great potential in cancer treatment, yet it is still largely unexploited. Herein, a novel, injectable and NO‐releasing hydrogel (NO‐Gel) composed of α‐(nitrate ester) acetic acid‐modified amphiphilic copolymers is developed. To further convert released NO to RNS, glutathione (GSH)‐sensitive CuCys nanoparticles (NPs) and β‐lapachone (Lapa) are co‐loaded into the NO‐Gel. This hydrogel system possesses a temperature‐induced sol‐gel transition and can continuously liberate Lapa, CuCys NPs, and NO in vitro for up to 3 weeks. The sustained supply of Lapa can efficiently boost hydrogen peroxide (H2O2) concentration in cancer cells, and intracellular GSH can induce the rapid release of NO and the reduction of CuCys NPs. With elevating H2O2 levels and producing highly reactive Cu(I), the Cu(I)‐catalyzed Fenton‐like reaction is dramatically enhanced, resulting in the generation of abundant hydroxyl radicals (·OH), and the subsequent cascade reactions among ·OH, H2O2, and NO cause more lethal RNS pool. After a single peritumoral injection of the hydrogel system, the cascade generation of ROS and RNS plus the substantial depletion of GSH can significantly suppress tumor growth.