In Situ Deposition of Drug and Gene Nanoparticles on a Patterned Supramolecular Hydrogel to Construct a Directionally Osteochondral Plug

The integrated repair of bone and cartilage boasts advantages for osteochondral restoration such as a long-term repair effect and less deterioration compared to repairing cartilage alone.Constructing multifactorial,spatially oriented scaffolds to stimulate osteochondral regeneration,has immense significance.Herein,targeted drugs,namely kartogenin@polydopamine(KGN@PDA)nanoparticles for cartilage repair and miRNA@calcium phosphate(miRNA@CaP)NPs for bone regeneration,were in situ deposited on a patterned supramolecular-assembled 2-ureido-4[lH]-pyrimidinone(UPy)modified gelation hydrogel film,facilitated by the dynamic and responsive coordination and complexation of metal ions and their ligands.This hydrogel film can be rolled into a cylindrical plug,mimicking the Haversian canal structure of natural bone.The resultant hydrogel demonstrates stable mechanical properties,a self-healing ability,a high capability for reactive oxygen species capture,and controlled release of KGN and miR-26a.In vitro,KGN@PDA and miRNA@CaP promote chondrogenic and osteogenic differentiation of mesenchymal stem cells via the JNK/RUNX1 and GSK-3β/β-catenin pathways,respectively.In vivo,the osteochondral plug exhibits optimal subchondral bone and cartilage regeneration,evidenced by a significant increase in glycosaminoglycan and collagen accumulation in specific zones,along with the successful integration of neocartilage with subchondral bone.This biomaterial delivery approach represents a significant toward improved osteochondral repair.

High quality repair of osteochondral defects in rats using the extracellular matrix of antler stem cells

BACKGROUND Cartilage defects are some of the most common causes of arthritis.Cartilage lesions caused by inflammation,trauma or degenerative disease normally result in osteochondral defects.Previous studies have shown that decellularized extracellular matrix(ECM)derived from autologous,allogenic,or xenogeneic mesenchymal stromal cells(MSCs)can effectively restore osteochondral integrity.AIM To determine whether the decellularized ECM of antler reserve mesenchymal cells(RMCs),a xenogeneic material from antler stem cells,is superior to the currently available treatments for osteochondral defects.METHODS We isolated the RMCs from a 60-d-old sika deer antler and cultured them in vitro to 70%confluence;50 mg/mL L-ascorbic acid was then added to the medium to stimulate ECM deposition.Decellularized sheets of adipocyte-derived MSCs(aMSCs)and antlerogenic periosteal cells(another type of antler stem cells)were used as the controls.Three weeks after ascorbic acid stimulation,the ECM sheets were harvested and applied to the osteochondral defects in rat knee joints.RESULTS The defects were successfully repaired by applying the ECM-sheets.The highest quality of repair was achieved in the RMC-ECM group both in vitro(including cell attachment and proliferation),and in vivo(including the simultaneous regeneration of well-vascularized subchondral bone and avascular articular hyaline cartilage integrated with surrounding native tissues).Notably,the antler-stem-cell-derived ECM(xenogeneic)performed better than the aMSC-ECM(allogenic),while the ECM of the active antler stem cells was superior to that of the quiescent antler stem cells.CONCLUSION Decellularized xenogeneic ECM derived from the antler stem cell,particularly the active form(RMC-ECM),can achieve high quality repair/reconstruction of osteochondral defects,suggesting that selection of decellularized ECM for such repair should be focused more on bioactivity rather than kinship.

A bibliometric analysis and visualization of osteochondral lesions of talus (2004-2021)

Background:Osteochondral lesions of the talus(OLTs)are a significant challenge for foot and ankle specialists,which could cause pain and decrease patient function.Researchers can use the findings of this study to shape future directions for research by exploring global trends and hotspots in OLT.Methods:Web of Science Core Collection was used to retrieve literature related to OLT between 2004 and 2021.This report covers the current state of OLTs,such as publications,journals,trends,hotspots,and the performances of relevant countries,institutions and authors.The co-citation analysis,the coauthorship analysis,the cooccurrence analysis,and the bibliographic coupling analysis were conducted with the Bibliometrix R package,VOSviewer v1.6.10.0,and CiteSpace 5.8.R3.Results:During an 18-year review,717 articles and 76 review articles on OLT published from 2004 to 2021 were reviewed.The USA has made the largest contribution to the OLT-related literature,and a significant contribution has been made by Kennedy JG(48/6.05%)and van Dijk CN(30/3.78%).In terms of total link strength,Foot&Ankle International was the leading journal.Analysis showed that the global research hotspots of OLTs focused on the pathogenesis,diagnosis,clinical research,and surgical treatment of OLT.It would be significant to pay close attention to future research on osteochondral autograft transplantation and management,surgery,multidisciplinary integration and mechanisms of OLT,and its related diseases.Conclusions:The study provides information about the current status and hotspots of research in the domain of OLT over the past 18 years that will assist researchers in identifying potential perspectives on hot topics and research frontiers.

Osteochondral tissue repair in osteoarthritic joints： clinical challenges and opportunities in tissue engineering

Osteoarthritis （OA）, identified as one of the priorities for the Bone and Joint Decade, is one of the most prevalent joint diseases, which causes pain and disability of joints in the adult population. Secondary OA usually stems from repetitive overloading to the osteochondral （OC） unit, which could result in cartilage damage and changes in the subchondral bone, leading to mechanical instability of the joint and loss of joint function. Tissue engineering approaches have emerged for the repair of cartilage defects and damages to the subchondral bone in the early stages of OA and have shown potential in restoring the joint＇s function. In this approach, the use of three-dimensional scaffolds （with or without cells） provides support for tissue growth. Commercially available OC scaffolds have been studied in OA patients for repair and regeneration of OC defects. However, none of these scaffolds has shown satisfactory clinical results. This article reviews the OC tissue structure and the design, manufacturing and performance of current OC scaffolds in treatment of OA. The findings demonstrate the importance of biological and biomechanical fixations of OC scaffolds to the host tissue in achieving an improved cartilage fill and a hyaline-like tissue formation. Achieving a strong and stable subchondral bone support that helps the regeneration of overlying cartilage seems to be still a grand challenge for the early treatment of OA.

Current management of talar osteochondral lesions

Osteochondral lesions of the talus(OLT) occur in up to 70% of acute ankle sprains and fractures. OLT have become increasingly recognized with the advancements in cartilage-sensitive diagnostic imaging modalities. Although OLT may be treated nonoperatively, a number of surgical techniques have been described for patients whom surgery is indicated. Traditionally, treatment of symptomatic OLT have included either reparative procedures, such as bone marrow stimulation(BMS), or replacement procedures, such as autologous osteochondral transplantation(AOT). Reparative procedures are generally indicated for OLT < 150 mm^2 in area. Replacement strategies are used for large lesions or after failed primary repair procedures. Although shortand medium-term results have been reported, longterm studies on OLT treatment strategies are lacking. Biological augmentation including platelet-rich plasma and concentrated bone marrow aspirate is becoming increasingly popular for the treatment of OLT to enhance the biological environment during healing. In this review, we describe the most up-to-date clinical evidence of surgical outcomes, as well as both the mechanical and biological concerns associated with BMS and AOT. In addition, we will review the recent evidence for biological adjunct therapies that aim to improve outcomes and longevity of both BMS and AOT procedures.

Establishing proof of concept:Platelet-rich plasma and bone marrow aspirate concentrate may improve cartilage repair following surgical treatment for osteochondral lesions of the talus

Osteochondral lesions of the talus are common injuries in the athletic patient. They present a challenging clinical problem as cartilage has a poor potential for healing. Current surgical treatments consist of reparative(microfracture) or replacement(autologous osteochondral graft) strategies and demonstrate good clinical outcomes at the short and medium term follow-up. Radiological findings and second-look arthroscopy however, indicate possible poor cartilage repair with evidence of fibrous infill and fissuring of the regenerative tissue following microfracture. Longer-term follow-up echoes these findings as it demonstrates a decline in clinical outcome. The nature of the cartilage repair that occurs for an osteochondral graft to become integrated with the native surround tissue is also of concern. Studies have shown evidence of poor cartilage integration,with chondrocyte death at the periphery of the graft, possibly causing cyst formation due to synovial fluid ingress. Biological adjuncts, in the form of platelet-rich plasma(PRP) and bone marrow aspirate concentrate(BMAC), have been investigated with regard to their potential in improving cartilage repair in both in vitro and in vitro settings. The in vitro literature indicates that these biological adjuncts may increase chondrocyte proliferation as well as synthetic capability, while limiting the catabolic effects of an inflammatory joint environment. These findings have been extrapolated to in vitro animal models, with results showing that both PRP and BMAC improve cartilage repair. The basic science literature therefore establishes the proof of concept that biological adjuncts may improve cartilage repair when used in conjunction with reparative and replacement treatment strategies for osteochondral lesions of the talus.

Platelet-rich plasma increases transforming growth factor-beta1 expression at graft-host interface following autologous osteochondral transplantation in a rabbit model

AIM: To explore the effect of platelet-rich plasma on protein expression patterns of transforming growth factor-beta1(TGF-β1) in cartilage following autologous osteochondral transplantation(AOT) in a rabbit knee cartilage defect model.METHODS: Twelve New Zealand white rabbits received bilateral AOT. In each rabbit, one knee was randomized to receive an autologous platelet rich plasma(PRP) injection and the contralateral knee received saline injection. Rabbits were euthanized at 3, 6 and 12 wk post-operatively. Articular cartilage sections were stained with TGF-β1 antibody. Histological regions of interest(ROI)(left, right and center of the autologous grafts interfaces) were evaluated using Meta Morph. Percentage of chondrocytes positive for TGF-β1 was then assessed.RESULTS: Percentage of chondrocytes positive for TGF-β1 was higher in PRP treated knees for selected ROIs(left; P = 0.03, center; P = 0.05) compared to control and was also higher in the PRP group at each post-operative time point(P = 6.6 × 10^(-4), 3.1 × 10^(-4) and 7.3 × 10^(-3) for 3, 6 and 12 wk, respectively). TGF-β1 expression was higher in chondrocytes of PRP-treated knees(36% ± 29% vs 15% ± 18%)(P = 1.8 × 10^(-6)) overall for each post-operative time point and ROI. CONCLUSION: Articular cartilage of rabbits treated with AOT and PRP exhibit increased TGF-β1 expression compared to those treated with AOT and saline. Our findings suggest that adjunctive PRP may increase TGF-β1 expression, which may play a role in the chondrogenic effect of PRP in vivo.

Scaffolds based therapy for osteochondral lesions of the talus:A systematic review

AIM To clarify the effectiveness of scaffold-based therapy for osteochondral lesions of the talus(OLT). METHODS A systematic search of MEDLINE and EMBASE databases was performed during August 2016 and updated in January 2017. Included studies were evaluated with regard to the level of evidence(LOE) and quality of evidence(QOE) using the Modified Coleman Methodology Score. Variable reporting outcome data, clinical outcomes, and the percentage of patients who returned to sport at previous level were also evaluated. RESULTS Twenty-eight studies for a total of 897 ankles were included; 96% were either LOE Ⅲ or Ⅳ. Studies were designated as either of poor or fair quality. There were 30 treatment groups reporting six different scaffold repair techniques: 13 matrix-induced autologous chondrocyte transplantation(MACT), nine bone marrow derived cell transplantation(BMDCT), four autologous matrixinduced chondrogeneis(AMIC), and four studies of other techniques. The categories of general demographics(93%) and patient-reported outcome data(85%) were well reported. Study design(73%), imaging data(73%), clinical variables(49%), and patient history(30%) were also included. The weighted mean American Orthopaedic Foot and Ankle Society(AOFAS) score at final follow-up was: 86.7 in MACT, 88.2 in BMDCT, and 82.3 in AMIC. Eight studies reported that a weighted mean of 68.3% ofpatients returned to a previous level of sport activity. CONCLUSION Scaffold-based therapy for OLT may produce favorable clinical outcomes, but low LOE, poor QOE, and variability of the data have confounded the effectiveness of this treatment.

In vivo evaluation of additively manufacturedmulti-layered scaffold for the repair of large osteochondral defects

The repair of osteochondral defects is one of the major clinical challenges in orthopaedics.Well-established osteochondral tissue engineering methods have shown promising results for the early treatment of small defects.However,less success has been achieved for the regeneration of large defects,which is mainly due to the mechanical environment of the joint and the heterogeneous nature of the tissue.In this study,we developed a multi-layered osteochondral scaffold to match the heterogeneous nature of osteochondral tissue by harnessing additive manufacturing technologies and combining the established art laser sintering and material extrusion techniques.The developed scaffold is based on a titanium and polylactic acid matrix-reinforced collagen“sandwich”composite system.The microstructure and mechanical properties of the scaffold were examined,and its safety and efficacy in the repair of large osteochondral defects were tested in an ovine condyle model.The 12-week in vivo evaluation period revealed extensive and significantly higher bone in-growth in the multi-layered scaffold compared with the collagen–HAp scaffold,and the achieved stable mechanical fixation provided strong support to the healing of the overlying cartilage,as demonstrated by hyaline-like cartilage formation.The histological examination showed that the regenerated cartilage in the multi-layer scaffold group was superior to that formed in the control group.Chondrogenic genes such as aggrecan and collagen-II were upregulated in the scaffold and were higher than those in the control group.The findings showed the safety and efficacy of the cell-free“translation-ready”osteochondral scaffold,which has the potential to be used in a one-step surgical procedure for the treatment of large osteochondral defects.

Knee salvage procedures: The indications, techniques and outcomes of large osteochondral allografts

The overall incidence of osteochondral defect in the general population is estimated to be 15 to 30 per100000 people.These lesions can become symptomatic causing pain,swelling and decreased function of the knee,and may eventually progress to osteoarthritis.In the young and active population,partial or total knee arthroplasty(TKA)is rarely the treatment of choice due to risk of early failure.Osteochondral allograft transplantation has been demonstrated to be a safe and effective treatment of large osteochondral and chondral defects of the knee in appropriately selected patients.The treatment reduces pain,improves function and is a viable limb salvage procedure for patients,especially young and active patients for whom TKA is not recommended.Either large dowels generated with commercially available equipment or free hand shell allografts can be implanted in more posterior lesions.Current recommendations for fresh allografts stored at4C advise implantation within 21-28 d of procurement for optimum chondrocyte viability,following screening and testing protocols.Higher rates of successful allograft transplantation are observed in younger patients,unipolar lesions,normal or corrected malalignment,and defects that are treated within 12 mo of symptom onset.Patients with bipolar lesions,uncorrectable malalignment,advanced osteoarthritis,and those over40 tend to have less favourable outcomes.

Current researches on design and manufacture of biopolymer-based osteochondral biomimetic scaffolds

Currently,osteochondral(OC)tissue engineering has become a potential treatment strategy in repairing chondral lesions and early osteoarthritis due to the limited self-healing ability of cartilage.However,it is still challenging to ensure the integrity,physiological function and regeneration ability of stratified OC scaffolds in clinical application.Biomimetic OC scaffolds are attractive to overcome the above problems because of their similar biological and mechanical properties with native OC tissue.As a consequence,the researches on biomimetic design to achieve the tissue function of each layer,and additive manufacture(AM)to accomplish composition switch and ultrastructure of personalized OC scaffolds have made a remarkable progress.In this review,the design methods of biomaterial and structure as well as computer-aided design,and performance prediction of biopolymer-based OC scaffolds are presented;then,the characteristics and limitations of AM technologies and the integrated manufacture schemes in OC tissue engineering are summarized;finally,the novel biomaterials and techniques and the inevitable trends of multifunctional bio-manufacturing system are discussed for further optimizing production of tissue engineering OC scaffolds.

Clinical efficacy of the Ankle Spacer for the treatment of multiple secondary osteochondral lesions of the talus

BACKGROUND The Ankle Spacer was developed as a joint-sparing alternative to invasive endstage surgeries.Currently,there are no clinical studies on the Ankle Spacer.AIM To describe the operative technique and the clinical efficacy of the Ankle Spacer for the treatment of multiple,cystic osteochondral lesions of the talus in patients with failed prior operative treatment.METHODS This is a prospective study during which patients were assessed preoperatively,at 2-and 6 wk,and at 3,6,12 and 24 mo postoperatively.Patients with multiple,cystic or large(≥15 mm)osteochondral lesions of the talus after failed prior surgery were included.The primary outcome measure was the numeric rating scale(NRS)for pain during walking at 2 years postoperatively.Secondary outcome measures included the NRS in rest and during stair climbing,the American Orthopaedic Foot and Ankle Society Hindfoot Score,the Foot and Ankle Outcome Score,the Short-Form 36 physical and mental component scale,and the Range of Motion(ROM).Radiographic evaluations were conducted to evaluate prosthetic loosening and subsidence.Revision rates and complications were also assessed.RESULTS Two patients underwent an Ankle Spacer implantation on the talus.The NRS during walking improved from 6 and 7 preoperatively to 2 and 2 points postoperatively at 2 years,in patient 1 and 2,respectively.The other patient-reported outcome measures also improved substantially.There were no re-operations nor complications.Radiological imaging showed no loosening of the implant and no change of implant position.CONCLUSION The Ankle Spacer showed clinically relevant pain reduction during walking,improvement in clinical outcomes as assessed with PROMs,and no complications or re-operations.This treatment option may evolve as a joint-sparing alternative to invasive end-stage surgeries.

Effects of Early Weightbearing on Microfracture Treatment of Osteochondral Lesions of Talus with Subchondral Bone Defects

When subchondral bone defects are present in osteochondral lesions of the talus(OCLT),it is inconclusive whether to allow early weightbearing after microfracture treatment because of the lack of effective support of the newly-formed fibrocartilage.After performing arthroscopic debridement and microfracture treatment on OCLT patients with subchondral bone defects,we allowed patients to have an early postoperative weightbearing exercise to observe their clinical outcome.Forty-two OCLT patients with subchondral bone defects were analyzed.Patients were randomly divided into two groups with 21 patients in each group.After arthroscopic debridement and microfracture treatment,group A was allowed to have early partial weightbearing while weightbearing was delayed in group B.Visual analogue scale(VAS)was used to evaluate joint pain before and after surgery.American Orthopaedic Foot and Ankle Society(AOFAS)anklc-hindfoot score was used to evaluate joint function.Tegner activity scale was used to assess patient's exercise level.The AOFAS ankle-hindfoot score in group A increased from 54.4 to 87.6,and that in group B increased from 54.9 to 87.3.The VAS score in group A decreased from 6.5 to 2.2,and that in group B decreased from 6.4 to 2.3.The Tegner activity scale increased from 2.6 to 4.4 in group A,and that in group B increased from 2.6 to 3.9.There was significant difference in the Tegner activity scale between group A and group B(P<0.05).It was suggested that when performing microfracture treatmenf on OCLT patients with subchondral bone defects,early postoperative weightbearing may achieve similar clinical outcomes as delayed weightbearing,and patients may be better able to return to sports.

Current advances in solid free-form techniques for osteochondral tissue engineering

Osteochondral （OC） lesions are characterized by defects in two different zones, the cartilage region and subchondral bone region. These lesions are frequently associated with mechanical instability, as well as osteoarthritic degenerative changes in the knee. The lack of spontaneous healing and the drawbacks of the current treatments have increased the attention from the scientific community to this issue. Different tissue engineering approaches have been attempted using different polymers and different scaffolds＇ processing. However, the current conventional techniques do not allow the full control over scaffold fabrication, and in this type of approaches, the tuning ability is the key to success in tissue regeneration. In this sense, the researchers have placed their efforts in the development of solid free-form （SFF） techniques. These techniques allow tuning different properties at the micro-macro scale, creating scaffolds with appropriate features for OC tissue engineering. In this review, it is discussed the current SFF techniques used in OC tissue engineering and presented their promising results and current challenges.

Systematic review of bone marrow stimulation for osteochondral lesion of talus-evaluation for level and quality of clinical studies

AIM To clarify the quality of the studies indicating lesion size and/or containment as prognostic indicators of bone marrow stimulation(BMS) for osteochondral lesions of the talus(OLT). METHODS Two reviewers searched the Pub Med/MEDLINE and EMBASE databases using specific terms on March 2015 in accordance with the Preferred Reporting Items for Systemic Reviews and Meta-Analyses guidelines. Predetermined variables were extracted for all the included studies. Level of evidence(LOE) was determined using previously published criteria by the Journal of Bone and Joint Surgery and methodological quality of evidence (MQOE) was evaluated using the Modified Coleman Methodology Score. RESULTS This review included 22 studies. Overall, 21 of the 22(95.5%) included studies were level Ⅳ or level Ⅲ evidences. The remaining study was a level Ⅱ evidence. MQOE analysis revealed 14 of the 22(63.6%) included studies having fair quality, 7(31.8%) studies having poor quality and only 1 study having excellent quality. CONCLUSION The evidence supporting the use of lesion size and containment as prognostic indicators of BMS for OLTs has been shown to be of low quality.

Osteochondral lesion of talus with gout tophi deposition:A case report

BACKGROUND Osteochondral lesion of talus is a broad term used to describe an injury or abnormality of the talar articular cartilage and adjacent bone.It arises from diverse causes,and although trauma is implicated in many cases,it does not account for the etiology of every lesion.Gout is a chronic arthritic disease caused by excess levels of uric acid in blood.Intraosseous deposition of monosodium urate in the clavicle,femur,patella and calcaneus was reported previously.Gout is common disease but rare at a young age,especially during teenage years.Osteochondral lesion caused by intra-articular gouty invasion is very rare.CASE SUMMARY We encountered a rare case of a 16-year-old male who has osteochondral lesion of the talus(OLT)with gout.He had fluctuating pain for more than 2 years.We could see intra-articular tophi with magnetic resonance image(MRI)and arthroscopy.We performed arthroscopic exploration,debridement and microfracture.Symptoms were resolved after operation,and bony coverage at the lesion was seen on postoperative images.We had checked image and uric acid levels for 18 mo.CONCLUSION It is rare to see OLT with gouty tophi in young adults.While it is challenging,the accuracy of diagnosis can be improved through history taking,MRI and arthroscopy.

Case Report: Osteochondral Fragment—A Rare Cause of Locked Metacarpophalangeal Joint

We describe the presentation of a patient with sudden, sharp pain associated with a snapping sensation, swelling and pain over the metacarpophalangeal joint (MCPJ) with no history of direct trauma. The finger was held in 30 degrees of flexion and significantly deviated to the ulnar side with loss of extension. A diagnosis of traumatic rupture of the radial sagittal band of the extensor mechanism was made but the cause at exploration was found to be impingement of an osteochondral fracture fragment. This is a rare cause of irreducible loose body ‘locking’ of the metacarpophalangeal joint.

3D printing of patient-specific implants for osteochondral defects: workflow for an MRI-guided zonal design

Magnetic resonance imaging(MRI)is a common clinical practice to visualize defects and to distinguish different tissue types and pathologies in the human body.So far,MRI data have not been used to model and generate a patient-specific design of multilayered tissue substitutes in the case of interfacial defects.For orthopedic cases that require highly individual surgical treatment,implant fabrication by additive manufacturing holds great potential.Extrusion-based techniques like 3D plot-ting allow the spatially defined application of several materials,as well as implementation of bioprinting strategies.With the example of a typical multi-zonal osteochondral defect in an osteochondritis dissecans(OCD)patient,this study aimed to close the technological gap between MRI analysis and the additive manufacturing process of an implant based on dif-ferent biomaterial inks.A workflow was developed which covers the processing steps of MRI-based defect identification,segmentation,modeling,implant design adjustment,and implant generation.A model implant was fabricated based on two biomaterial inks with clinically relevant properties that would allow for bioprinting,the direct embedding of a patient’s own cells in the printing process.As demonstrated by the geometric compatibility of the designed and fabricated model implant in a stereolithography(SLA)model of lesioned femoral condyles,a novel versatile CAD/CAM workflow was successfully established that opens up new perspectives for the treatment of multi-zonal(osteochondral)defects.

Type II collagen scaffolds repair critical-sized osteochondral defects under induced conditions of osteoarthritis in rat knee joints via inhibiting TGF-β-Smad1/5/8 signaling pathway

The bidirectional relationship between osteochondral defects(OCD)and osteoarthritis(OA),with each condition exacerbating the other,makes OCD regeneration in the presence of OA challenging.Type II collagen(Col2)is important in OCD regeneration and the management of OA,but its potential applications in cartilage tissue engineering are significantly limited.This study investigated the regeneration capacity of Col2 scaffolds in critical-sized OCDs under surgically induced OA conditions and explored the underlying mechanisms that promoted OCD regeneration.Furthermore,the repair potential of Col2 scaffolds was validated in over critical-sized OCD models.After 90 days or 150 days since scaffold implantation,complete healing was observed histologically in critical-sized OCD,evidenced by the excellent integration with surrounding native tissues.The newly formed tissue biochemically resembled adjacent natural tissue and exhibited comparable biomechanical properties.The regenerated OA tissue demonstrated lower expression of genes associated with cartilage degradation than native OA tissue but comparable expression of genes related to osteochondral anabolism compared with normal tissue.Additionally,transcriptome and proteome analysis revealed the hindrance of TGF-β-Smad1/5/8 in regenerated OA tissue.In conclusion,the engrafting of Col2 scaffolds led to the successful regeneration of critical-sized OCDs under surgically induced OA conditions by inhibiting the TGF-β-Smad1/5/8 signaling pathway.

Full-thickness osteochondral defect repair using a biodegradable bilayered scaffold of porous zinc and chondroitin sulfate hydrogel

The regeneration of osteochondral tissue necessitates the re-establishment of a gradient owing to the unique characteristics and healing potential of the chondral and osseous phases.As the self-healing capacity of hyaline cartilage is limited,timely mechanical support during neo-cartilage formation is crucial to achieving optimal repair efficacy.In this study,we devised a biodegradable bilayered scaffold,comprising chondroitin sulfate(CS)hydrogel to regenerate chondral tissue and a porous pure zinc(Zn)scaffold for regeneration of the underlying bone as mechanical support for the cartilage layer.The photocured CS hydrogel possessed a compressive strength of 82 kPa,while the porous pure Zn scaffold exhibited a yield strength of 11 MPa and a stiffness of 0.8 GPa.Such mechanical properties are similar to values reported for cancellous bone.In vitro biological experiments demonstrated that the bilayered scaffold displayed favorable cytocompatibility and promoted chondrogenic and osteogenic differentiation of bone marrow stem cells.Upon implantation,the scaffold facilitated the simultaneous regeneration of bone and cartilage tissue in a porcine model,resulting in(i)a smoother cartilage surface,(ii)more hyaline-like cartilage,and(iii)a superior integration into the adjacent host tissue.Our bilayered scaffold exhibits significant potential for clinical application in osteochondral regeneration.