Department of Biomedicine, University Hospital Basel, University of Basel, Switzerland; Department of Biomedical Engineering, University of Basel, Switzerland.
Ospedale Policlinico San Martino-IST, IRCCS per l'Oncologia, Genova, Italy.
Adv Drug Deliv Rev. 2018 Apr;129:285-294. doi: 10.1016/j.addr.2018.01.010. Epub 2018 Jan 31.
Bone tissue has a strong intrinsic regenerative capacity, thanks to a delicate and complex interplay of cellular and molecular processes, which tightly involve the immune system. Pathological settings of anatomical, biomechanical or inflammatory nature may lead to impaired bone healing. Innovative strategies to enhance bone repair, including the delivery of osteoprogenitor cells or of potent cytokines/morphogens, indicate the potential of 'orthobiologics', but are not fully satisfactory. Here, we review different approaches based on the delivery of regenerative cues produced by cells but in cell-free, possibly off-the-shelf configurations. Such strategies exploit the paracrine effect of the secretome of mesenchymal stem/stromal cells, presented in soluble form, shuttled through extracellular vesicles, or embedded within the network of extracellular matrix molecules. In addition to osteoinductive molecules, attention is given to factors targeting the resident immune cells, to reshape inflammatory and immunity processes from scarring to regenerative patterns.
骨组织具有强大的内在再生能力，这要归功于细胞和分子过程的精细而复杂的相互作用，这些过程紧密涉及免疫系统。解剖学、生物力学或炎症性质的病理环境可能导致骨愈合受损。增强骨修复的创新策略，包括输送成骨前体细胞或有效细胞因子/形态发生素，表明了“orthobiologics”的潜力，但并不完全令人满意。在这里，我们回顾了基于细胞产生的再生线索的不同方法，但这些方法是无细胞的，可能是现成的。这些策略利用间充质干细胞（MSC）分泌组的旁分泌作用，以可溶性形式呈现，通过细胞外囊泡转运，或嵌入细胞外基质分子网络中。除了成骨诱导分子外，还关注针对驻留免疫细胞的因子，以重塑炎症和免疫过程，从瘢痕形成到再生模式。
