Bone microenvironment regulative hydrogels with ROS scavenging and prolonged oxygen-generating for enhancing bone repair

Large bone defects resulting from fractures and disease are a major clinical challenge,being often unable to heal spontaneously by the body’s repair mechanisms.Lines of evidence have shown that hypoxia-induced overproduction of ROS in bone defect region has a major impact on delaying bone regeneration.However,replenishing excess oxygen in a short time cause high oxygen tension that affect the activity of osteoblast precursor cells.Therefore,reasonably restoring the hypoxic condition of bone microenvironment is essential for facilitating bone repair.Herein,we designed ROS scavenging and responsive prolonged oxygen-generating hydrogels(CPP-L/GelMA)as a“bone microenvironment regulative hydrogel”to reverse the hypoxic microenvironment in bone defects region.CPP-L/GelMA hydrogels comprises an antioxidant enzyme catalase(CAT)and ROS-responsive oxygen-releasing nanoparticles(PFC@PLGA/PPS)co-loaded liposome(CCP-L)and GelMA hydrogels.Under hypoxic condition,CPP-L/GelMA can release CAT for degrading hydrogen peroxide to generate oxygen and be triggered by superfluous ROS to continuously release the oxygen for more than 2 weeks.The prolonged oxygen enriched microenvironment generated by CPP-L/GelMA hydrogel significantly enhanced angiogenesis and osteogenesis while inhibited osteoclastogenesis.Finally,CPP-L/GelMA showed excellent bone regeneration effect in a mice skull defect model through the Nrf2-BMAL1-autophagy pathway.Hence,CPP-L/GelMA,as a bone microenvironment regulative hydrogel for bone tissue respiration,can effectively scavenge ROS and provide prolonged oxygen supply according to the demand in bone defect region,possessing of great clinical therapeutic potential.

Analysis of the relationship between liver-qi stagnation and premature ovarian failure based on exosomes

The incidence of premature ovarian failure,which is related to women’s excessive pressure and mental tension,has increased in recent years.Premature ovarian failure has become one of the diseases that seriously disturb women’s physical and mental health,and its incidence can be regarded as liver depression and qi stagnation.Patients have an increasing demand for treatment,not only for fertility with the improvement of social living standards and the development of healthcare technology.Exosomes,as small membrane vesicles containing complex RNA and proteins,have the function of mediating cell communication and transmitting information in the pathological state caused by liver-qi stagnation.Exosomes in the hypoxic microenvironment can protect cells from damage and promote the pathological process.Moreover,exosomes in an inflammatory environment can play an active anti-inflammatory role.Exosomes can reduce the apoptosis of granulosa cells by expressing miRNA and so on to restore ovarian function.The purpose of treating premature ovarian failure can be achieved in this way.This paper introduced the relationship between the three,discussed the guiding significance of Chinese medicine theories in the treatment of exosomes and premature ovarian failure,and provided new research ideas for the treatment of integrated traditional Chinese medicine and western medicine.

Hypoxia response element-directed expression of bFGF in dental pulp stem cells improve the hypoxic environment by targeting pericytes in SCI rats

Cell-based transplantation strategies possess great potential for spinal cord injury(SCI)repair.Basic fibroblast growth factor(bFGF)has been reported to have multiple neuro-promoting effects on developing and adult nervous system of mammals and considered a promising therapy for nerve injury following SCI.Human dental pulp stem cells(DPSCs)are abundant stem cells with low immune rejection,which can be considered for cell replacement therapy.The purpose of this study was to investigate the roles of DPSCs which express bFGF under the regulation of five hypoxia-responsive elements(5HRE)using an adeno-associated virus(AAV-5HRE-bFGF-DPSCs)in SCI repairing model.In this study,DPSCs were revealed to differentiate into CD13^(+)pericytes and up-regulate N-cadherin expression to promote the re-attachment of CD13^(+)pericytes to vascular endothelial cells.The re-attachment of CD13^(+)pericytes to vascular endothelial cells subsequently increased the flow rate of blood in microvessels via the contraction of protuberance.As a result,increased numbers of red blood cells carried more oxygen to the damaged area and the local hypoxia microenvironment in SCI was improved.Thus,this study represents a step forward towards the potential use of AAV-5HRE-bFGF-DPSCs in SCI treatment in clinic.