RESUMO
Deep burns are one of the most severe skin wounds, with typical symptoms being a contradiction between initial severe pain and a subsequent loss of sensation. Although it has long been known that sensory nerves promote skin regeneration and modulate skin function, no proven burn management strategies target sensory nerves. Here, a neuro-inspired biomimetic microreactor is designed based on the immune escape outer membrane of neuroblastoma cells and neural-associated intracellular proteins. The microreactor is constructed on a metal-organic framework (MOF) with a neuroblastoma membrane coating the surface and intracellular proteins loaded inside, called Neuro-MOF. It is loaded into a therapeutic hydrogel and triggers the release of its content proteins upon excitation by near-infrared light. The proteins compensate the skin microenvironment for permanent neurological damage after burns to initiate peripheral nerve regeneration and hair follicle niche formation. In addition, the neuroblastoma cell membrane is displayed on the surface of the Neuro-MOF microreactor, decreasing its immunogenicity and suppressing local inflammation. In a mouse model of deep skin burns, the Neuro-MOF microreactor exhibited significant functional skin regeneration effects, particularly sensory recovery and hair follicle neogenesis.
Assuntos
Queimaduras , Neuroblastoma , Camundongos , Animais , Folículo Piloso , Cicatrização/fisiologia , Biomimética , Pele , Microambiente TumoralRESUMO
Sonodynamic therapy (SDT) has considerable potential in cancer treatment and exhibits high tissue penetration with minimal damage to healthy tissues. The efficiency of SDT is constrained by the complex immunological environment and tumor treatment resistance. Herein, a specific acoustic-actuated tumor-targeted nanomachine is proposed to generate mechanical damage to lysosomes for cancer SDT. The hybrid nanomachine was assembled with gold nanoparticles (GNPs) as the core and encapsulated with macrophage exosomes modified by AS1411 aptamers (GNP@EXO-APs) to optimize the pharmacokinetics and tumor aggregation. GNP@EXO-APs could be specifically transferred to the lysosomes of tumor cells. After induction with ultrasound, GNP@EXO-APs generated strong mechanical stress to produce lysosomal-dependent cell death in cancer cells. Notably, tumor-associated macrophages were reprogrammed in the ultrasound environment to an antitumor phenotype. Enhanced mechanical destruction via GNP@EXO-APs and immunotherapy of cancer cells were verified both in vitro and in vivo under SDT. This study provides a new direction for inside-out killing effects on tumor cells for cancer treatment.
RESUMO
The use of biomaterials in regenerative medicine has expanded to treat various disorders caused by trauma or disease in orthopedics and dentistry. However, the treatment of large and complex bone defects presents a challenge, leading to a pressing need for optimized biomaterials for bone repair. Recent advances in chemical sciences have enabled the incorporation of therapeutic ions into bone grafts to enhance their performance. These ions, such as strontium (for bone regeneration/osteoporosis), copper (for angiogenesis), boron (for bone growth), iron (for chemotaxis), cobalt (for B12 synthesis), lithium (for osteogenesis/cementogenesis), silver (for antibacterial resistance), and magnesium (for bone and cartilage regeneration), among others (e.g., zinc, sodium, and silica), have been studied extensively. This review aims to provide a comprehensive overview of current knowledge and recent developments in ion incorporation into biomaterials for bone and periodontal tissue repair. It also discusses recently developed biomaterials from a basic design and clinical application perspective. Additionally, the review highlights the importance of precise ion introduction into biomaterials to address existing limitations and challenges in combination therapies. Future prospects and opportunities for the development and optimization of biomaterials for bone tissue engineering are emphasized.