Elevated fluid and glycosaminoglycan content in the Achilles tendon contribute to higher intratendinous pressures:Implications for Achilles tendinopathy

Background:Tendinopathy alters the compositional properties of the Achilles tendon by increasing fluid and glycosaminoglycan content.It has been speculated that these changes may affect intratendinous pressure,but the extent of this relationship remains unclear.Therefore,we aimed to investigate the impact of elevated fluid and glycosaminoglycan content on Achilles tendon intratendinous pressure and to determine whether hyaluronidase(HYAL) therapy can intervene in this potential relationship.Methods:Twenty paired fresh-frozen cadaveric Achilles tendons were mounted in a tensile-testing machine and loaded up to 5% strain.Intratendinous resting(at 0% strain) and dynamic pressure(at 5% strain) were assessed using the microcapillary infusion technique.First,intratendinous pressure was measured under native conditions before and after infusion of 2 mL physiological saline.Next,80 mg of glycosaminoglycans were administered bilaterally to the paired tendons.The right tendons were additionally treated with 1500 units of HYAL.Finally,both groups were retested,and the glycosaminoglycan content was analyzed.Results:It was found that both elevated fluid and glycosaminoglycan content resulted in higher intratendinous resting and dynamic pressures(p <0.001).HYAL treatment induced a 2.3-fold reduction in glycosaminoglycan content(p=0.002) and restored intratendinous pressures.Conclusion:The results of this study demonstrated that elevated fluid and glycosaminoglycan content in Achilles tendinopathy contribute to increased intratendinous re sting and dynamic pressures,which can be explained by the associated increased volume and reduced permeability of the tendon matrix,respectively.HYAL degrades glycosaminoglycans sufficiently to lower intratendinous pressures and may,therefore,serve as a promising treatment.

Multi-omics analysis of human tendon adhesion reveals that ACKR1-regulated macrophage migration is involved in regeneration

Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies,resulting in severe disability.Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation.However,different clusters of macrophages have various functions and receive multiple regulation,which are both still unknown.In our current study,multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury.The transcriptomes of over 74000 human single cells were profiled.As results,we found that SPP1^(+)macrophages,RGCC^(+)endothelial cells,ACKR1^(+)endothelial cells and ADAM12^(+)fibroblasts participated in tendon adhesion formation.Interestingly,despite specific fibrotic clusters in tendon adhesion,FOLR2^(+)macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells.Furthermore,ACKR1 was verified to regulate FOLR2^(+)macrophages migration at the injured peritendinous site by transplantation of bone marrow from Lysm-Cre;R26R^(tdTomato) mice to lethally irradiated Ackr1^(-/-)mice(Ackr1^(-/-)chimeras;deficient in ACKR1)and control mice(WT chimeras).Compared with WT chimeras,the decline of FOLR2^(+)macrophages was also observed,indicating that ACKR1 was specifically involved in FOLR2^(+)macrophages migration.Taken together,our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis,but also uncovered a novel antifibrotic cluster of macrophages and their origin.These results provide potential therapeutic targets against human tendon adhesion.

Animal models of tendon calcification:Past,present,and future

Tendon calcification is a common clinical condition that frequently occurs as a complication after tendon injury and surgery,or as an expression of fibrodysplasia ossificans progressiva.This condition can be referred to by various names in clinical practice and literature,including tendon ossification,tendon mineralization,heterotopic ossification,and calcific tendonitis.The exact pathogenesis of tendon calcification remains uncertain,but current mainstream research suggests that calcification is mostly cell mediated.To further elucidate the pathogenesis of tendon calcification and to better simulate the overall process,selecting appropriate experimental animal models is important.Numerous animal models have been utilized in various clinical studies,each with its own set of advantages and limitations.In this review,we have discussed the advancements made in research on animal models of tendon calcification,with a focus on the selection of experimental animals,the sites of injury in these models,and the methods employed for modeling.

A tendon system to re-center steel moment frames with weak stories

A wide open bottom story of a frame building is often expected by owners for use as a garage or shops.However,this leads to weak stories due to abrupt changes in lateral stiffness and often results in unexpected story collapse as observed in many previous earthquakes.To retrofit frame buildings that have experienced weak story damage,a tendon system is proposed in this study,which consists of a set of swaying columns and tendons.The swaying columns are used to uniformly redistribute the lateral deformation along the height,while the tendons provide extra lateral stiffness and renders the entire structural system a re-centering capability.To avoid unnecessary forces to swaying columns,pin-connections are used at the bottom.Tendons are placed over the entire story to gain large elastic displacements.Parametric analysis reveals that the swaying column,with a stiffness of about 0.9 times that of the weak story,and the tendons attached at the roof,with a stiffness of 0.04 times that of the weak story,can provide the optimal performance with a maximum residual story drift angle of less than 0.5%.Online hybrid tests were carried out,which demonstrated that uniformly distributed story drifts and acceptable residual deformation could be achieved by the proposed tendon system.

Brachioradialis tendon transfer and palmaris longus tendon graft for thumb avulsion:A case report and review of literature

BACKGROUND Thumb replantation following complete traumatic avulsion requires complex techniques to restore function,especially in cases of avulsion at the level of the metacarpophalangeal joint(MCP I)and avulsion of the flexor pollicis longus(FPL)at the musculotendinous junction.Possible treatments include direct tendon suture or tendon transfer,most commonly from the ring finger.To optimize function and avoid donor finger complications,we performed thumb replantation with flexion restoration using brachioradialis(BR)tendon transfer with palmaris longus(PL)tendon graft.CASE SUMMARY A 20-year-old left-handed male was admitted for a complete traumatic left thumb amputation following an accident while sliding from the top of a handrail.The patient presented with skin and bone avulsion at the MCP I,avulsion of the FPL tendon at the musculotendinous junction(zone 5),avulsion of the extensor pollicis longus tendon(zone T3),and avulsion of the thumb’s collateral arteries and nerves.The patient was treated with two stage thumb repair.The first intervention consisted of thumb replantation with MCP I arthrodesis,resection of avulsed FPL tendon and implantation of a silicone tendon prosthesis.The second intervention consisted of PL tendon graft and BR tendon transfer.Follow-up at 10 months showed good outcomes with active interphalangeal flexion of 70°,grip strength of 45 kg,key pinch strength of 15 kg and two-point discrimination threshold of 4 mm.CONCLUSION Flexion restoration after complete thumb amputation with FPL avulsion at the musculotendinous junction can be achieved using BR tendon transfer with PL tendon graft.

Tendoscopic Surgery for Peroneal Tendons Instability: A Literature Review

Introduction: There has been a surge in the use of tendoscopic surgery for treating peroneal tendons instability. The novelty of this approach demanded a literature review of its indications, limitations, and clinical outcomes. Aim: a literature review of the clinical studies reporting on tendoscopic peroneal tendon stabilisation surgery along with its outcomes and complications. Methods: We carried out a comprehensive review of the literature up until September 2022 with an extensive search of the MEDLINE, Embase and Cochrane library databases. Results: Initial search resulted in 66 articles. Four duplicate articles were removed. Further 30 articles were excluded after title and abstract screening. Eight studies satisfied the inclusion criteria and were included in this review. Articles were analysed for outcomes and complications. Conclusion: The tendoscopic technique for peroneal tendon instability is an effective and safe surgical technique with very low failure rate. Levels of Evidence: Level IV.

Correlation of Hamstring Tendon Size in Pre-Operative MRI Measurement with Intra-Operative Graft Size in Primary Anterior Cruciate Ligament (ACL) Reconstruction

Background: The size of Hamstring autograft of less than 8.0 mm in ACL re-construction is one of the key factors that may contribute to the failure of the graft. In this study, we are going to assess the correlation of pre-operative MRI measurement of Hamstring tendons with the intra-operative ACL graft. Thus, it may help surgeons to anticipate the needs for graft augmentation should the final graft size be smaller than expected. Methods: We retrospectively re-viewed 41 cases of ACL reconstructions in which MRI were done pre-operatively, in Hospital Pakar Sultanah Fatimah (HPSF), Muar between January 2019 until December 2022. MRI measurements of Hamstring tendon (semitendinosus: ST, and gracilis) were done by a radiologist, and the in-tra-operative notes were reviewed for the final graft size. Pearson’s correlation coefficients were calculated to determine the relationship between graft size and tendon cross-sectional area. The intraclass correlation (ICC) by using two-way mixed model with type consistency, the reliability based on average measure was 0.41 (95% CI: ?0.10, 0.69). A p-value < 0.05 was considered sig-nificant. Results: Of 105 patients with primary ACL reconstruction done be-tween January 2019 to December 2022, only 41 patients were included in this study. There was fair correlation (p = 0.048) between pre-operative MRI measurement and the graft diameter intra-operatively. The mean of 17.0 mm of combined diameter of ST and gracilis tendon in MRI may results in graft diameter of 8.3 mm. There was also positive correlation between patients’ height and the intra-operative graft size. Conclusion: These results showed good correlation between pre-operative MRI measurement of Hamstring ten-don size with the intra-operative graft size, hence it is a reliable tool to predict the Hamstring autograft size in ACL reconstruction.

Adenylate cyclase activates the cAMP signalling pathway to enhance platelet-rich plasma-treated Achilles tendon disease,a theoretical bioinformatics-based study

The effectiveness of platelet-rich plasma(PRP)for the treatment of Achilles tendon disorders still needs to be evaluated through a series of prospective studies,but genomic analysis can reveal the existence of complementary PRP treatment options.Based on the 96 platelet activation-related genes in the Kyoto Encyclopedia of Genes and Genomes(KEGG)database,we performed Gene Ontology functional enrichment analysis and KEGG enrichment analysis,pathway correlation analysis,and enrichment mapping to determine the enrichment results of the gene set enrichment analysis and found that the cAMP signalling pathway may be the key to enhancing the effectiveness of PRP treatment.The cAMP signalling pathway interacts with the Rap1 signalling pathway and cGMPPKG signalling pathway to mediate the entire pathophy-siological process of Achilles tendon disease.Moreover,ADCY1-9 may be the key to the activation of the cAMP signalling network.Further based on the data in the Gene Expression Omnibus database,it was found that ADCY4 and ADCY7 may be the players that play a major role,associated with the STAT4-ADCY4-LAMA5 axis and the GRbeta-ADCY7-SEMA3C axis,which is expected to be a complementary target for enhancing the efficacy of PRP in the treatment of Achilles tendon disease.

Bipolar hip arthroplasty using conjoined tendon preserving posterior lateral approach in treatment of displaced femoral neck fractures

BACKGROUND Hip fractures account for 23.8%of all fractures in patients over the age of 75 years.More than half of these patients are older than 80 years.Bipolar hemiarthroplasty(BHA)was established as an effective management option for these patients.Various approaches can be used for the BHA procedure.However,there is a high risk of postoperative dislocation.The conjoined tendon-preserving posterior(CPP)lateral approach was introduced to reduce postoperative dislocation rates.AIM To evaluate the effectiveness and safety of the CPP lateral approach for BHA in elderly patients.METHODS We retrospectively analyzed medical data from 80 patients with displaced femoral neck fractures who underwent BHA.The patients were followed up for at least 1 year.Among the 80 patients,57(71.3%)were female.The time to operation averaged 2.3 d(range:1-5 d).The mean age was 80.5 years(range:67-90 years),and the mean body mass index was 24.9 kg/m^(2)(range:17-36 kg/m^(2)).According to the Garden classification,42.5%of patients were typeⅢand 57.5%of patients were typeⅣ.Uncemented bipolar hip prostheses were used for all patients.Torn conjoined tendons,dislocations,and adverse complications during and after surgery were recorded.RESULTS The mean postoperative follow-up time was 15.3 months(range:12-18 months).The average surgery time was 52 min(range:40-70 min)with an average blood loss of 120 mL(range:80-320 mL).The transfusion rate was 10%(8 of 80 patients).The gemellus inferior was torn in 4 patients(5%),while it was difficult to identify in 2 patients(2.5%)during surgery.The posterior capsule was punctured by the fractured femoral neck in 3 patients,but the conjoined tendon and the piriformis tendon remained intact.No patients had stem varus greater than 3 degrees or femoral fracture.There were no patients with stem subsidence more than 5 mm at the last follow-up.No postoperative dislocations were observed throughout the follow-up period.No significance was found between preoperative and postoperative mean Health Service System scores(87.30±2.98 vs 86.10±6.10,t=1.89,P=0.063).CONCLUSION The CPP lateral approach can effectively reduce the incidence of postoperative dislocation without increasing perioperative complications.For surgeons familiar with the posterior lateral approach,there is no need for additional surgical instruments,and it does not increase surgical difficulty.

Application of real-time shear wave elastography to Achilles tendon hardness evaluation in older adults

BACKGROUND Real-time shear wave elastography(SWE)is a non-invasive imaging technique used to measure tissue stiffness by generating and tracking shear waves in real time.This advanced ultrasound-based method provides quantitative information regarding tissue elasticity,offering valuable insights into the mechanical properties of biological tissues.However,the application of real-time SWE in the musculoskeletal system and sports medicine has not been extensively studied.AIM To explore the practical value of real-time SWE for assessing Achilles tendon hardness in older adults.METHODS A total of 60 participants were enrolled in the present study,and differences in the elastic moduli of the bilateral Achilles tendons were compared among the following categories:(1)Age:55-60,60-65,and 65-70-years-old;(2)Sex:Male and female;(3)Laterality:Left and right sides;(4)Tendon state:Relaxed and tense state;and(5)Tendon segment:Proximal,middle,and distal.RESULTS There were no significant differences in the elastic moduli of the bilateral Achilles tendons when comparing by age or sex(P>0.05).There were,however,significant differences when comparing by tendon side,state,or segment(P<0.05).CONCLUSION Real-time SWE plays a significant role compared to other examination methods in the evaluation of Achilles tendon hardness in older adults.

Insights and implications from the study on meniscus reconstruction using tendon autograft

This letter addresses the recent study by Zhu et al on the predictive factors for coronal and sagittal graft extrusion length following medial meniscus reconstruction using tendon autografts.The study provides valuable insights into the importance of preoperative joint space width and tunnel positioning as predictors of graft extrusion.Specifically,it found strong correlations between preoperative joint space width and medial,posterior,and mean graft extrusion at both 1 week and 8 months post-operation.Additionally,tunnel edge distance at 1 week postoperation correlated with anterior and posterior graft extrusion.These findings offer critical guidance for improving surgical outcomes.However,the letter highlights the need for further research with larger sample sizes and comparative studies involving different graft types to strengthen these findings and broaden their applicability in clinical settings.The study's contributions to understanding meniscus reconstruction using tendon autografts are acknowledged,along with suggestions for future research directions.

Presentation and management outcome of foot drop with tibialis posterior tendon transfer

BACKGROUND Foot drop causes considerable disability.The ankle-dorsiflexion is either weak or lost completely.Additionally,the ankle eversion and toe extensions are also impaired.This results in a high steppage gait while walking.Overall,the gait is awkward;there is greater energy consumption;increased proneness to sustain injury of the forefoot;and more frequent falling during walking.AIM To document the clinical and epidemiological profile of foot drop patients in our population and evaluate the outcome of tibialis posterior(TP)tendon transfer for restoring the lost dorsiflexion in foot drop.METHODS The study was carried out at the National Institute of Rehabilitation Medicine in Islamabad over a period of 7 years.It included patients of all sexes and ages who presented with foot drop and had no contraindications for the procedure of TP tendon transfer.Exclusion criteria were patients who had contraindications for the operation.For instance,paralyzed posterior leg compartment muscles,Achilles tendon contracture,stiff ankle or toes,unstable ankle joint,weak gastrocnemius and scarred skin spanning over the route of planned tendon transfer.Also,patients who had the foot drop as a result of disc prolapses or brain diseases were excluded.Convenience sampling technique was used.The circum-tibial route of TP tendon transfer was employed.RESULTS Out of 37 patients,26(70.27%)were males whereas 11(29.72%)were females.The mean age was 22.59±8.19 years.Among the underlying causes of foot drop,road traffic accidents constituted the most common cause,found among 20(54.05%)patients.The share of complications included wound infections in 3(8.10%)patients and hypertrophic scars in 2(5.40%)patients.At 1-year postoperative follow-up visits,the outcome was excellent in 8(21.62%),good in 20(54.05%)and moderate in 9(24.31%).CONCLUSION The majority of cases of foot drop resulted from road traffic accidents that directly involved the common peroneal nerve.TP tendon transfer through the circumtibial route was found to be an easily executed effective operation which restored good dorsiflexion of the ankle among the majority of patients.

Transplantation of tissue-engineered human corneal epithelium in limbal stem cell deficiency rabbit models

AIM: To evaluate the biological functions of tissue-engineered human corneal epithelium (TE-HCEP) by corneal transplantation in limbal stem cell deficiency (LSCD) rabbit models. METHODS: TE-HCEPs were reconstructed with DiI-labeled untransfected HCEP cells and denuded amniotic membrane (dAM) in air-liquid interface culture, and their morphology and structure were characterized by hematoxylin-eosin (HE) staining of paraffin-sections, immunohistochemistry and electron microscopy. LSCD models were established by mechanical and alcohol treatment of the left eyes of New Zealand white rabbits, and their eyes were transplanted with TE-HCEPs with dAM surface outside by lamellar keratoplasty (LKP). Corneal transparency, neovascularization, thickness, and epithelial integrality of both traumatic and post transplantation eyes were checked once a week by slit-lamp corneal microscopy, a corneal pachymeter, and periodic acid-Schiff (PAS) staining. At day 120 post surgery, the rabbits in each group were sacrificed and their corneas were examined by DiI label observation, HE staining, immunohistochemistry and electron microscopy. RESULTS: After cultured for 5 days on dAM, HCEP cells, maintaining keratin 3 expression, reconstructed a 6-7 layer TE-HCEP with normal morphology and structure. The traumatic rabbit corneas, entirely opaque, conjunctivalized and with invaded blood vessels, were used as LSCD models for TE-HCEP transplantation. After transplantation, obvious edema was not found in TE-HCEP-transplanted corneas which became more and more transparent, the invaded blood vessels reduced gradually throughout the monitoring period. The corneas decreased to normal thickness on day 25, while those of dAM eyes were over 575 mu m in thickness during the monitoring period. A 45 layer of epithelium consisting of TE-HCEP originated cells attached tightly to the anterior surface of stroma was reconstructed 120 days after TE-HCEP transplantation, which was similar to the normal control eye in morphology and structure. In contrast, intense corneal edema, turbid, invaded blood vessels were found in dAM eyes, and no multilayer epithelium was found but only a few scattered conjunctiva-like cells appeared. CONCLUSION: The TE-HCEP, with similar morphology and structure to those of innate HCEP, could reconstruct a multilayer corneal epithelium with normal functions in restoring corneal transparency and thickness of LSCD rabbits after transplantation. It may be a promising HCEP equivalent for clinical therapy of corneal epithelial disorders.

In vitro reconstruction and characterization of tissue-engineered human corneal epithelium with seeder cells from an untransfected human corneal epithelial cell line

AIM: To demonstrate the morphology and structure of in vitro reconstructed tissue-engineered human corneal epithelium (TE-HCEP) with seeder cells from an untransfected HCEP cell line. METHODS: The TE-HCEPs were reconstructed in vitro with seeder cells from an untransfected HCEP cell line, and scaffold carriers of denuded amniotic membrane (dAM) in air-liquid interface culture for 3, 5, 7 and 9 days, respectively. The specimens were examined with hematoxylin-eosin (HE) staining of paraffin-section, immunocytochemical staining, scanning and transmission electron microscopy. RESULTS: During in vitro reconstruction of TE-HCEP, HCEP cells formed a 3-4, 6-7 and 8-10 layers of an HCEP-like structure on dAMs in air-liquid interface culture for 3, 5 and 7 days, respectively. But the cells deceased to 5-6 layers and the structure of straified epithelium became loose at day 9. And the cells maintained positive expression of marker proteins (keratin 3 and keratin 12), cell-junction proteins (zonula occludens-1, E-cadherin, connexin 43 and integrin beta 1) and membrane transport protein of Na+-K+ ATPase. The HCEP cells in TE-HCEP were rich in microvilli on apical surface and established numerous cell-cell and cell-dAM junctions at day 5. CONCLUSION: The morphology and structure of the reconstructed TE-HCEP were similar to those of HCEP in vivo. The HCEP cells in the reconstructed TE-HCEP maintained the properties of HCEP cells, including abilities of forming intercellular and cell-extracellular matrix junctions and abilities of performing membrane transportation. The untransfected HCEP cells and dAMs could promisingly be used in reconstruction HCEP equivalent for clinical corneal epithelium transplantation.

Bridging sciatic nerve gap using tissue-engineered nerves constructed with neural tissue-committed stem cells derived from bone marrow

BACKGROUND： Schwann cells are the most commonly used cells for tissue-engineered nerves. However, autologous Schwann cells are of limited use in a clinical context, and allogeneic Schwann cells induce immunological rejections. Cells that do not induce immunological rejections and that are relatively easy to acquire are urgently needed for transplantation. OBJECTIVE： To bridge sciatic nerve defects using tissue engineered nerves constructed with neural tissue-committed stem cells （NTCSCs） derived from bone marrow; to observe morphology and function of rat nerves following bridging; to determine the effect of autologous nerve transplantation, which serves as the gold standard for evaluating efficacy of tissue-engineered nerves. DESIGN, TIME AND SETTING： This randomized, controlled, animal experiment was performed in the Anatomical Laboratory and Biomedical Institute of the Second Military Medical University of Chinese PLA between September 2004 and April 2006. MATERIALS： Five Sprague Dawley rats, aged 1 month and weighing 100-150 g, were used for cell culture. Sixty Sprague Dawley rats aged 3 months and weighing 220-250 g, were used to establish neurological defect models. Nestin, neuron-specific enolase （NSE）, glial fibrillary acidic protein （GFAP）, and S-100 antibodies were provided by Santa Cruz Biotechnology, Inc., USA. Acellular nerve grafts were derived from dogs. METHODS： All rats, each with 1-cm gap created in the right sciatic nerve, were randomly assigned to three groups. Each group comprised 20 rats. Autograft nerve transplantation group： the severed 1-cm length nerve segment was reverted, but with the two ends exchanged; the proximal segment was sutured to the distal sciatic nerve stump and the distal segment to the proximal stump. Blank nerve scaffold transplantation group： a 1-cm length acellular nerve graft was used to bridge the sciatic nerve gap. NTCSC engineered nerve transplantation group： a 1-cm length acellular nerve graft, in which NTCSCs were inoculated, was used to bridge the sciatic nerve gap. MAIN OUTCOME MEASURES： Following surgery, sciatic nerve functional index and electrophysiology functions were evaluated for nerve conduction function, including conduction latency, conduction velocity, and action potential peak. Horseradish peroxidase （HRP, 20%） was injected into the gastrocnemius muscle to retrogradely label the 1-4 and L5 nerve ganglions, as well as neurons in the anterior horn of the spinal cord, in the three groups. Positive expression of nestin, NSE, GFAP, and S-100 were determined using an immunofluorescence double-labeling method. RESULTS： NTCSCs differentiated into neuronal-like cells and glial-like cells within 12 weeks after NTCSC engineered nerve transplantation. HRP retrograde tracing displayed a large amount of HRP-labeled neurons in I-45 nerve ganglions, as well as the anterior horn of the spinal cord, in both the autograft nerve transplantation and the NTCSC engineered nerve transplantation groups. However, few HRP-labeled neurons were detected in the blank nerve scaffold transplantation group. Nerve bridges in the autograft nerve transplantation and NTCSC engineered nerve transplantation groups exhibited similar morphology to normal nerves. Neither fractures or broken nerve bridges nor neuromas were found after bridging the sciatic nerve gap with NTCSCs-inoculated acellular nerve graft, indicating repair. Conduction latency, action potential, and conduction velocity in the NTCSC engineered nerve transplantation group were identical to the autograft nerve transplantation group （P 〉 0.05）, but significantly different from the blank nerve scaffold transplantation group （P 〈 0.05）. CONCLUSION＂ NTCSC tissue-engineered nerves were able to repair injured nerves and facilitated restoration of nerve conduction function, similar to autograft nerve transplantation. ＂

Angiogenesis in tissue-engineered nerves evaluated objectively using MICROFIL perfusion and micro-CT scanning

Angiogenesis is a key process in regenerative medicine generally, as well as in the specific field of nerve regeneration. However, no convenient and objective method for evaluating the angiogenesis of tissue-engineered nerves has been reported. In this study, tissue-engineered nerves were constructed in vitro using Schwann cells differentiated from rat skin-derived precursors as supporting cells and chitosan nerve conduits combined with silk fibroin fibers as scaffolds to bridge 10-mm sciatic nerve defects in rats. Four weeks after surgery, three-dimensional blood vessel reconstructions were made through MICROFIL perfusion and micro-CT scanning, and parameter analysis of the tissue-engineered nerves was performed. New blood vessels grew into the tissue-engineered nerves from three main directions： the proximal end, the distal end, and the middle. The parameter analysis of the three-dimensional blood vessel images yielded several parameters, including the number, diameter, connection, and spatial distribution of blood vessels. The new blood vessels were mainly capillaries and microvessels, with diameters ranging from 9 to 301 μm. The blood vessels with diameters from 27 to 155 μm accounted for 82.84% of the new vessels. The microvessels in the tissue-engineered nerves implanted in vivo were relatively well-identified using the MICROFIL perfusion and micro-CT scanning method, which allows the evaluation and comparison of differences and changes of angiogenesis in tissue-engineered nerves implanted in vivo.

Tppp3~+synovial/tendon sheath progenitor cells contribute to heterotopic bone after trauma

Heterotopic ossification(HO)is a pathological process resulting in aberrant bone formation and often involves synovial lined tissues.During this process,mesenchymal progenitor cells undergo endochondral ossification.Nonetheless,the specific cell phenotypes and mechanisms driving this process are not well understood,in part due to the high degree of heterogeneity of the progenitor cells involved.Here,using a combination of lineage tracing and single-cell RNA sequencing(sc RNA-seq),we investigated the extent to which synovial/tendon sheath progenitor cells contribute to heterotopic bone formation.For this purpose,Tppp3(tubulin polymerization-promoting protein family member 3)-inducible reporter mice were used in combination with either Scx(Scleraxis)or Pdgfra(platelet derived growth factor receptor alpha)reporter mice.Both tendon injury-and arthroplasty-induced mouse experimental HO models were utilized.Sc RNA-seq of tendon-associated traumatic HO suggested that Tppp3 is an early progenitor cell marker for either tendon or osteochondral cells.Upon HO induction,Tppp3 reporter^(+)cells expanded in number and partially contributed to cartilage and bone formation in either tendon-or joint-associated HO.In double reporter animals,both Pdgfra^(+)Tppp3^(+)and Pdgfra^(+)Tppp3^(-) progenitor cells gave rise to HO-associated cartilage.Finally,analysis of human samples showed a substantial population of TPPP3^(-) expressing cells overlapping with osteogenic markers in areas of heterotopic bone.Overall,these data demonstrate that synovial/tendon sheath progenitor cells undergo aberrant osteochondral differentiation and contribute to HO after trauma.

Tissue-engineered nerve for repair of sciatic nerve injury

Three articles regarding the use of nerve fragments bridging regeneration chambers, three-dimensional bionic nerve conduits and multiwalled carbon nanotubes for repair of sciatic nerve injury were reported in Neural Regeneration Research. We hope that our readers find these papers useful to their research.

Effectiveness of platelet-rich plasma in the treatment of Achilles tendon disease

BACKGROUND The effectiveness of Platelet-Rich Plasma(PRP)in the treatment of patients with Achilles tendon rupture(ATR)and Achilles tendinopathy(AT)has been controversial.AIM To assess PRP injections’effectiveness in treating ATR and AT.METHODS A comprehensive review of relevant literature was conducted utilizing multiple databases such as Cochrane Library,PubMed,Web of Science,Chinese Science and Technology Journal,EMBASE,and China Biomedical CD-ROM.The present investigation integrated randomized controlled trials that assessed the effectiveness of platelet-rich plasma injections in managing individuals with Achilles tendon rupture and tendinopathy.The eligibility criteria for the trials encompassed publications that were published within the timeframe of January 1,1966 to December 2022.The statistical analysis was performed utilizing the Review Manager 5.4.1,the visual analogue scale(VAS),Victorian Institute Ankle Function Scale(VISA-A),and Achilles Tendon Thickness were used to assess outcomes.RESULTS This meta-analysis included 13 randomized controlled trials,8 of which were randomized controlled trials of PRP for AT and 5 of which were randomized controlled trials of PRP for ATR.PRP for AT at 6 wk[weighted mean difference(WMD)=1.92,95%CI:-0.54 to 4.38,I2=34%],at 3 mo[WMD=0.20,95%CI:-2.65 to 3.05,I2=60%],and 6 mo[WMD=2.75,95%CI:-2.76 to 8.26,I2=87%)after which there was no significant difference in VISA-A scores between the PRP and control groups.There was no significant difference in VAS scores between the PRP group and the control group after 6 wk[WMD=6.75,95%CI:-6.12 to 19.62,I2=69%]and 6 mo[WMD=10.46,95%CI:-2.44 to 23.37,I2=69%]of treatment,and at mid-treatment at 3 mo[WMD=11.30,95%CI:7.33 to 15.27,I2=0%]after mid-treatment,the PRP group demonstrated better outcomes than the control group.Post-treatment patient satisfaction[WMD=1.07,95%CI:0.84 to 1.35,I2=0%],Achilles tendon thickness[WMD=0.34,95%CI:-0.04 to 0.71,I2=61%]and return to sport[WMD=1.11,95%CI:0.87 to 1.42,I2=0%]were not significantly different between the PRP and control groups.The study did not find any statistically significant distinction between the groups that received PRP treatment and those that did not,regarding the Victorian Institute of Sport Assessment-Achilles scores at 3 mo[WMD=-1.49,95%CI:-5.24 to 2.25,I2=0%],6 mo[WMD=-0.24,95%CI:-3.80 to 3.32,I2=0%],and 12 mo[WMD=-2.02,95%CI:-5.34 to 1.29,I2=87%]for ATR patients.Additionally,no significant difference was observed between the PRP and the control groups in improving Heel lift height respectively at 6 mo[WMD=-3.96,95%CI:-8.61 to 0.69,I2=0%]and 12 mo[WMD=-1.66,95%CI:-11.15 to 7.83,I2=0%]for ATR patients.There was no significant difference in calf circumference between the PRP group and the control group after 6 mo[WMD=1.01,95%CI:-0.78 to 2.80,I2=54%]and 12 mo[WMD=-0.55,95%CI:-2.2 to 1.09,I2=0%]of treatment.There was no significant difference in ankle mobility between the PRP and control groups at 6 mo of treatment[WMD=-0.38,95%CI:-2.34 to 1.58,I2=82%]and after 12 mo of treatment[WMD=-0.98,95%CI:-1.41 to-0.56,I2=10%]there was a significant improvement in ankle mobility between the PRP and control groups.There was no significant difference in the rate of return to exercise after treatment[WMD=1.20,95%CI:0.77 to 1.87,I2=0%]and the rate of adverse events[WMD=0.85,95%CI:0.50 to 1.45,I2=0%]between the PRP group and the control group.CONCLUSION The use of PRP for AT improved the patient’s immediate VAS scores but not VISA-A scores,changes in Achilles tendon thickness,patient satisfaction,or return to sport.Treatment of ATR with PRP injections alone improved long-term ankle mobility but had no significant effect on VISA-A scores,single heel lift height,calf circumference or return to sport.Additional research employing more extensive sampling sizes,more strict experimental methods,and standard methodologies may be necessary to yield more dependable and precise findings.

Preliminary studies of constructing a tissue-engineered lamellar corneal graft by culturing mesenchymal stem cells onto decellularized corneal matrix

AIM:To construct a competent corneal lamellar substitute in order to alleviate the shortage of human corneal donor.METHODS:Rabbit mesenchymal stem cells(MSCs)were isolated from bone marrow and identified by flow cytometric,osteogenic and adipogenic induction.Xenogenic decellularized corneal matrix(XDCM)was generated from dog corneas.MSCs were seeded and cultured on XDCM to construct the tissueengineered cornea.Post-transplantation biocompatibility of engineered corneal graft were tested by animal experiment.Rabbits were divided into two groups then underwent lamellar keratoplasty(LK)with different corneal grafts:1)XDCM group(n=5):XDCM;2)XDCM-MSCs groups(n=4):tissue-engineered cornea made up with XDCM and MSCs.The ocular surface recovery procedure was observed while corneal transparency,neovascularization and epithelium defection were measured and compared.In vivo on focal exam was performed 3 mo postoperatively.RESULTS:Rabbit MSCs were isolated and identified.Flow cytometry demonstrated isolated cells were CD90 positive and CD34,CD45 negative.Osteogenic and adipogenic induction verified their multipotent abilities.MSC-XDCM grafts were constructed and observed.In vivo transplantation showed the neovascularization in XDCMMSC group was much less than that in XDCM group postoperatively.Post-transplant 3-month confocal test showed less nerve regeneration and bigger cell-absent area in XDCM-MSC group.CONCLUSION:This study present a novel corneal tissue-engineered graft that could reduce post-operatively neovascularization and remain transparency,meanwhile shows that co-transplantation of MSCs may help increase corneal transplantation successful rate and enlarge the source range of corneal substitute to overcome cornea donor shortage.