In vivo imaging of the neuronal response to spinal cord injury:a narrative review

Deciphering the neuronal response to injury in the spinal cord is essential for exploring treatment strategies for spinal cord injury(SCI).However,this subject has been neglected in part because appropriate tools are lacking.Emerging in vivo imaging and labeling methods offer great potential for observing dynamic neural processes in the central nervous system in conditions of health and disease.This review first discusses in vivo imaging of the mouse spinal cord with a focus on the latest imaging techniques,and then analyzes the dynamic biological response of spinal cord sensory and motor neurons to SCI.We then summarize and compare the techniques behind these studies and clarify the advantages of in vivo imaging compared with traditional neuroscience examinations.Finally,we identify the challenges and possible solutions for spinal cord neuron imaging.

Clinical guidelines for indications,techniques,and complications of autogenous bone grafting

Autogenous bone grafts have long been considered the“gold standard”and most effective material in bone regeneration procedures.[1]Autogenous bone grafts are used to repair bone defects caused by nonunion,infection,tumor resection,and spinal and joint fusion.[2]It has been reported that more than 200,000 autologous bone grafts are performed in the United States each year.[3]Although there are no specific statistics on the annual number of bone grafts performed in China,autologous bone grafting is the most common surgical technique in orthopedics.The iliac crest remains the most common donor site,along with the fibula,ribs,tibial metaphysis,proximal humerus,distal radius,and greater trochanter.[4,5]Various bone-graft options provide different amounts and qualities of cortical,cancellous,and corticocancellous bone.[6,7]Autogenous bone graft is osteogenic,histocompatible,provides structural support.

Adhesive hydrogels in osteoarthritis:from design to application

Osteoarthritis(OA)is the most common type of degenerative joint disease which affects 7%of the global population and more than 500 million people worldwide.One research frontier is the development of hydrogels for OA treatment,which operate either as functional scaffolds of tissue engineering or as delivery vehicles of functional additives.Both approaches address the big challenge:establishing stable integration of such delivery systems or implants.Adhesive hydrogels provide possible solutions to this challenge.However,few studies have described the current advances in using adhesive hydrogel for OA treatment.This review summarizes the commonly used hydrogels with their adhesion mechanisms and components.Additionally,recognizing that OA is a complex disease involving different biological mechanisms,the bioactive therapeutic strategies are also presented.By presenting the adhesive hydrogels in an interdisciplinary way,including both the fields of chemistry and biology,this review will attempt to provide a comprehensive insight for designing novel bioadhesive systems for OA therapy.

Skeleton-vasculature chain reaction: a novel insight into the mystery of homeostasis

Angiogenesis and osteogenesis are coupled.However,the cellular and molecular regulation of these processes remains to be further investigated.Both tissues have recently been recognized as endocrine organs,which has stimulated research interest in the screening and functional identification of novel paracrine factors from both tissues.This review aims to elaborate on the novelty and significance of endocrine regulatory loops between bone and the vasculature.In addition,research progress related to the bone vasculature,vessel-related skeletal diseases,pathological conditions,and angiogenesis-targeted therapeutic strategies are also summarized.With respect to future perspectives,new techniques such as single-cell sequencing,which can be used to show the cellular diversity and plasticity of both tissues,are facilitating progress in this field.Moreover,extracellular vesicle-mediated nuclear acid communication deserves further investigation.In conclusion,a deeper understanding of the cellular and molecular regulation of angiogenesis and osteogenesis coupling may offer an opportunity to identify new therapeutic targets.

Chitin scaffold combined with autologous small nerve repairs sciatic nerve defects

Although autologous nerve transplantation is the gold standard for treating peripheral nerve defects,it has many clinical limitations.As an alternative,various tissue-engineered nerve grafts have been developed to substitute for autologous nerves.In this study,a novel nerve graft composed of chitin scaffolds and a small autologous nerve was used to repair sciatic nerve defects in rats.The novel nerve graft greatly facilitated regeneration of the sciatic nerve and myelin sheath,reduced atrophy of the target muscle,and effectively restored neurological function.When the epineurium of the small autogenous nerve was removed,the degree of nerve regeneration was similar to that which occurs after autogenous nerve transplantation.These findings suggest that our novel nerve graft might eventually be a new option for the construction of tissue-engineered nerve scaffolds.The study was approved by the Research Ethics Committee of Peking University People's Hospital(approval No.2019 PHE27)on October 18,2019.

Early patellar tendon rupture after total knee arthroplasty: A direct repair method

BACKGROUND Patellar tendon rupture after total knee arthroplasty(TKA)is a catastrophic complication.Although the occurrence of this injury is rare,it can lead to significant dysfunction for the patient and is very tricky to deal with.There has been no standard treatment for early patella tendon rupture after TKA,and long-term follow-up data are lacking.AIM To introduce a direct repair method for early patella tendon rupture following TKA and determine the clinical outcomes and complications of this method.METHODS During the period of 2008 to 2021,3265 consecutive TKAs were retrospectively reviewed.Twelve patients developed early patellar tendon rupture postoperatively and were treated by a direct repair method.Mean follow-up was 5.7 years.Demographic,operative,and clinical data were collected.The clinical outcomes were assessed using the Western Ontario and McMaster Universities(WOMAC)score,the Hospital for Special Surgery(HSS)score,knee range of motion,extensor lag,and surgical complications.Descriptive statistics and paired t test were employed to analyze the data.RESULTS For all 12 patients who underwent direct repair for early patellar tendon rupture,3 patients failed:One(8.3%)for infection and two(17.6%)for re-fracture.The two patients with re-fracture both underwent reoperation to reconstruct the extensor mechanism and the patient with infection underwent revision surgery.The range of motion was 109.2°±10.6°preoperatively to 87.9°±11°postoperatively,mean extensor lag was 21°at follow-up,and mean WOMAC and HSS scores were 65.8±30.9 and 60.3±21.7 points,respectively.CONCLUSION This direct repair method of early patellar tendon rupture is not an ideal therapy.It is actually ineffective for the recovery of knee joint function in patients,and is still associated with severe knee extension lag and high complication rates.Compared with the outcomes of other repair methods mentioned in the literature,this direct repair method shows poor clinical outcomes.

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.

3D-printed fish gelatin scaffolds for cartilage tissue engineering

Knee osteoarthritis is a chronic disease caused by the deterioration of the knee joint due to various factors such as aging,trauma,and obesity,and the nonrenewable nature of the injured cartilage makes the treatment of osteoarthritis challenging.Here,we present a three-dimensional(3D)printed porous multilayer scaffold based on cold-water fish skin gelatin for osteoarticular cartilage regeneration.To make the scaffold,cold-water fish skin gelatin was combined with sodium alginate to increase viscosity,printability,and mechanical strength,and the hybrid hydrogel was printed according to a pre-designed specific structure using 3D printing technology.Then,the printed scaffolds underwent a double-crosslinking process to enhance their mechanical strength even further.These scaffolds mimic the structure of the original cartilage network in a way that allows chondrocytes to adhere,proliferate,and communicate with each other,transport nutrients,and prevent further damage to the joint.More importantly,we found that cold-water fish gelatin scaffolds were nonimmunogenic,nontoxic,and biodegradable.We also implanted the scaffold into defective rat cartilage for 12 weeks and achieved satisfactory repair results in this animal model.Thus,cold-water fish skin gelatin scaffolds may have broad application potential in regenerative medicine.

Chinese expert consensus on organ protection of transplantation(2022 edition)

Introduction Organ transplantation increases survival and improves qual-ity of life to many patients with end-stage organ failure.Or-gan shortage is a worldwide problem that restricts organ trans-plantation[1].Organ procurement and preservation as well as ischemia-reperfusion injury(IRI)after transplantation are the im-portant factors affecting prognosis of recipients.Since the de-velopment of organ transplantation technology in the 20th cen-tury,organ protection technology has been a most promising con-cept in this field.Organ preservation solutions such as the Collins solution,University of Wisconsin(UW)solution,and histidine-tryptophan-ketoglutarate(HTK)solution were developed sequen-tially[2],which developed rapidly in static cold storage(SCS)tech-niques.SCS remains the standard preservation technique for organ transplantation[2].

Fish scale-derived scaffolds with MSCs loading for photothermal therapy of bone defect

Tissue engineering scaffolds have presented effective value in bone repair.However,the integration of the diverse components,complex structures,multifunction to impart the scaffolds with improved applicability is still a challenge.Here,we propose a novel fish-derived scaffold combined with photothermal therapy and mesenchymal stem cells(MSCs)to promote bone regeneration.The fish-derived scaffold is composed of the decellularized fish scale and gelatin methacrylate synthesized from fish gelatin(fGelMA),which can promote the proliferation and osteogenesis of MSCs with no obvious immunological rejection.Furthermore,the black phosphorus(BP)nanosheets are incorporated into the fGelMA hydrogel network,which can endow the hydrogel with the capacity of photothermal conversion stimulated by near-infrared(NIR)light.The fish-derived scaffold can promote the osteogenesis process of MSCs with higher expression of osteogenic markers and higher mineralization assisted by the NIR light in vitro.The regeneration of mice calvarial defect has also been accelerated by the scaffold with photothermal therapy and MSCs.These results suggest that the fish-derived scaffold,photothermal therapy,MSCs-based regenerative therapy is a promising clinical strategy in bone regeneration.

Liposomalα-cyperone targeting bone resorption surfaces suppresses osteoclast differentiation and osteoporosis progression via the PI3K/Akt axis

Osteoporosis is a metabolic dysregulation of bone that occurs mainly in postmenopausal women,and the hyperfunction of osteoclasts is the primary contributor to postmenopausal osteoporosis.However,the development of effective therapeutic drugs and precise delivery systems remains a challenge in the field of anti-absorption therapy.Here,we reported theα-cyperone(α-CYP)for anti-osteoporosis and developed a liposome-based nano-drug delivery system ofα-CYP,that specifically targets the bone resorption interface.Firstly,we found that theα-CYP,one of the major sesquiterpenes of Cyperus rotundus L.,attenuated the progression of osteoporosis in ovariectomized(OVX)mice and down-regulated the expression of phosphorylated proteins of phosphoinositide 3-kinase(PI3K)and protein kinase B(Akt),causing down-regulation of osteoclast-related genes/proteins and curbing osteoclast differentiation.Furthermore,α-CYP reversed the activation of osteoclastic differentiation and enhanced osteoporosis-related proteins expression caused by PI3K/Akt agonist(YS-49).More importantly,we adopted the osteoclastic resorption surface targeting peptide Asp8 and constructed the liposome(lipαC@Asp8)to deliverα-CYP to osteoclasts and confirmed its anti-osteoporosis effect and enhanced osteoclast inhibition by blocking PI3K/Akt axis.In conclusion,this study demonstrated thatα-CYP inhibits osteoclast differentiation and osteoporosis development by silencing PI3K/Akt pathway,and the liposome targeting delivery systems loaded withα-CYP might provide a novel and effective strategy to treat osteoporosis.

Bone targeting antioxidative nano-iron oxide for treating postmenopausal osteoporosis

Osteoporosis is the most common degenerative orthopedic disease in the elderly.Recently,the therapeutic methods for osteoporosis have shifted towards the regulation of local immunity in bone tissues,which could provide a suitable environment for the positive regulation of bone metabolism,promoting osteogenic differentiation and inhibiting osteoclast differentiation.Our previous work demonstrated that iron oxide nanoparticles(IONPs)could positively regulate bone metabolism in vitro.In this study,we further demonstrated that daily administration of IONPs relieved estrogen deficiency-induced osteoporosis via scavenging reactive oxygen species in vivo.Meanwhile,IONPs promoted the osteogenic differentiation of bone marrow mesenchymal stem cells and inhibited the osteoclast differentiation of monocytes from IONPs treated mice.Besides,alendronate,a clinically used anti-osteoporosis bisphosphate,was employed to precisely deliver the IONPs to the bone tissues and played a synergically therapeutic role.Eventually,we verified the bone targeting ability,therapeutic efficiency,and biocompatibility of the novel bone target iron oxides in ovariectomy-induced osteoporotic mice.By applying BTNPs,the OVX-induced osteoporosis was significantly revised in mice models via the positive regulation of bone metabolism.

Nanoenzyme engineered neutrophil-derived exosomes attenuate joint injury in advanced rheumatoid arthritis via regulating inflammatory environment

Rheumatoid arthritis(RA)is a chronic inflammatory disease characterized by synovitis and destruction of cartilage,promoted by sustained inflammation.However,current treatments remain unsatisfactory due to lacking of selective and effective strategies for alleviating inflammatory environments in RA joint.Inspired by neutrophil chemotaxis for inflammatory region,we therefore developed neutrophil-derived exosomes functionalized with sub-5 nm ultrasmall Prussian blue nanoparticles(uPB-Exo)via click chemistry,inheriting neutrophil-targeted biological molecules and owning excellent anti-inflammatory properties.uPB-Exo can selectively accumulate in activated fibroblast-like synoviocytes,subsequently neutralizing pro-inflammatory factors,scavenging reactive oxygen species,and alleviating inflammatory stress.In addition,uPB-Exo effectively targeted to inflammatory synovitis,penetrated deeply into the cartilage and real-time visualized inflamed joint through MRI system,leading to precise diagnosis of RA in vivo with high sensitivity and specificity.Particularly,uPB-Exo induced a cascade of anti-inflammatory events via Th17/Treg cell balance regulation,thereby significantly ameliorating joint damage.Therefore,nanoenzyme functionalized exosomes hold the great potential for enhanced treatment of RA in clinic.