Endogenous repair theory enriches construction strategies for orthopaedic biomaterials:a narrative review

The development of tissue engineering has led to new strategies for mitigating clinical problems;however,the design of the tissue engineering materials remains a challenge.The limited sources and inadequate function,potential risk of microbial or pathogen contamination,and high cost of cell expansion impair the efficacy and limit the application of exogenous cells in tissue engineering.However,endogenous cells in native tissues have been reported to be capable of spontaneous repair of the damaged tissue.These cells exhibit remarkable plasticity,and thus can differentiate or be reprogrammed to alter their phenotype and function after stimulation.After a comprehensive review,we found that the plasticity of these cells plays a major role in establishing the cell source in the mechanism involved in tissue regeneration.Tissue engineering materials that focus on assisting and promoting the natural self-repair function of endogenous cells may break through the limitations of exogenous seed cells and further expand the applications of tissue engineering materials in tissue repair.This review discusses the effects of endogenous cells,especially stem cells,on injured tissue repairing,and highlights the potential utilisation of endogenous repair in orthopaedic biomaterial constructions for bone,cartilage,and intervertebral disc regeneration.

The endogenous progenitor response following traumatic brain injury:a target for cell therapy paradigms

Although there is ample evidence that central nervous system progenitor pools respond to traumatic brain injury,the reported effects are variable and likely contribute to both recovery as well as pathophysiology.Through a better understanding of the diverse progenitor populations in the adult brain and their niche-specific reactions to traumatic insult,treatments can be tailo red to enhance the benefits and dampen the deleterious effects of this response.This review provides an overview of endogenous precursors,the associated effects on cognitive recovery,and the potential of exogenous cell therapeutics to modulate these endogenous repair mechanisms.Beyond the hippocampal dentate gyrus and subventricular zone of the lateral ventricles,more recently identified sites of adult neurogenesis,the meninges,as well as circumventricular organs,are also discussed as targets for endogenous repair.Importantly,this review highlights that progenitor prolife ration alone is no longer a meaningful outcome and studies must strive to better chara cterize precursor spatial localization,transcriptional profile,morphology,and functional synaptic integration.With improved insight and a more targeted approach,the stimulation of endogenous neurogenesis remains a promising strategy for recovery following traumatic brain injury.

Electroacupuncture regulates the stress-injury-repair chain of events after cerebral ischemia/reperfusion injury

Inflammation after stroke is the main cause of cerebral ischemia/reperfusion injury. Cascading events after injury can lead to cell death. Heat shock protein 70 and other endogenous injury-signaling molecules are released by damaged cells, which can lead to systemic stress reactions. Protecting the brain through repair begins with the stress-injury-repair signaling chain. This study aimed to verify whether acupuncture acts through this chain to facilitate effective treatment of ischemic stroke. Rat models of cerebral ischemia/reperfusion injury were established by Zea Longa＇s method, and injury sites were identified by assessing neurological function, 2,3,5-triphenyltetrazolium chloride staining, and hematoxylin-eosin staining. Electroacupuncture at acupoints Baihui（DU20） and Zusanli（ST36） was performed in the model rats with dilatational waves, delivered for 20 minutes a day at 2–100 Hz and an amplitude of 2 m A. We analyzed the blood serum from the rats and found that inflammatory cytokines affected the levels of adrenotrophin and heat shock protein 70, each of which followed a similar bimodal curve. Specifically, electroacupuncture lowered the peak levels of adrenocorticotrophic hormone and heat shock protein 70. Thus, electroacupuncture was able to inhibit excessive stress, reduce inflammation, and promote the repair of neurons, which facilitated healing of ischemic stroke.

Dual and multi-drug delivery nanoparticles towards neuronal survival and synaptic repair

Among the macromolecular drug targets in neurodegenerative disorders, the neurotrophin brain-derived neurotrophic factor（BDNF） and its high-affinity tropomyosin-related kinase receptor（Trk B） present strong interest for nanomedicine development aiming at neuronal and synaptic repair. Currently, BDNF is regarded as the neurotrophic factor of highest therapeutic significance. However, BDNF has delivery problems as a protein drug. The enhanced activation of the transcription factor CREB（c AMP response element-binding protein） has been evidenced to increase the BDNF gene expression and hence the production of endogenous BDNF. We assume that BDNF delivery by nanocarriers and mitochondrial protection may provide high potential for therapeutic amelioration of the neuroregenerative strategies. Beneficial therapeutic outcomes may be expected for synergistic dual or multi-drug action aiming at（i） neurotrophic protein regulation in the central and peripheral nervous systems, and（ii） diminishment of the production of reactive oxygen species（ROS） and the oxidative damage in mitochondria. Our research strategy is based on a nanoarchitectonics approach for the design of nanomedicine assemblies by hierarchical self-assembly. We explore nanoarchitectonics concepts in soft-matter nanotechnology towards preparation of biodegradable self-assembled lipid nanostructures for safe neuro-therapeutic applications of multi-target nanomedicines.