Revision of anterior cruciate ligament (ACL) reconstruction is more challenging than primary ACL reconstruction and often yields less favorable outcomes. The European Society of Sports Traumatology, Knee Surgery and Arthroscopy (ESSKA) has established a consensus regarding preoperative diagnosis, assessment, and selection criteria for ACL revision surgery. This consensus addresses 18 key issues that are most pertinent to clinical practice, providing guiding recommendations aimed at improving the prognosis of ACL revisions.

Objective:To evaluate the mid-term effectiveness of limited unique coracoid osteotomy suture button fixation Latarjet (LU-tarjet) procedure in treatment of recurrent anterior shoulder dislocation. Methods:Between March 2017 and February 2019, 56 patients with recurrent shoulder dislocation were treated with arthroscopic LU-tarjet procedure. There were 44 males and 12 females with an average age of 26.3 years (range, 18-41 years). Shoulder joint dislocation occurred 2-16 times, with an average of 7.5 times. The time from the initial dislocation to operation ranged from 6 months to 13 years, with a median of 4.6 years. Preoperative shoulder joint fear test and re-reduction test were positive in all patients. The Beighton score of joint relaxation ranged from 1 to 7, with an average of 4.1. The shoulder Instability Severity Index Score (ISIS) ranged from 5 to 10, with an average of 7.8. The size of glenoid defects on the affected side ranged from 15% to 32% (mean, 22.4%). All patients had Hill-Sachs injuries of varying degrees. Six patients had re-dislocation after Bankart surgery. The operation time, incision healing, and postoperative complications were recorded. The range of motion (shoulder flexion, extension, abduction, external rotation, 90° external rotation, and internal rotation) and muscle strength in shoulder flexion, abduction, external rotation, and internal rotation) of shoulder joint were compared between pre- and post-operation. The improvement of shoulder function was evaluated using the American Association for Shoulder and Elbow Surgery (ASES) score, Walch-Duplay score, and Rowe score. X-ray films and three-dimensional CT were used to analyze the location, healing, and remolding of bone graft, the repair of glenoid defect, and degenerative changes of the shoulder joint. Results:All operations were successfully completed. The operation time ranged from 42 to 98 minutes, with an average of 63 minutes. All incisions healed by first intention. All patients were followed up 5-7 years (mean, 6.3 years). During follow-up, 2 patients experienced shoulder subluxation within 1 year after operation and 1 patient experienced recurrent shoulder joint pain. The remaining patients had no related complications. At last follow-up, there was no significant difference between the two groups ( P>0.05) in range of motion (shoulder flexion, extension, abduction, external rotation, 90° external rotation, and internal rotation) and muscle strength in shoulder flexion, abduction, external rotation, and internal rotation). The ASES score, Rowe score, and Walch-Duplay score of shoulder significantly improved when compared with those before operation ( P<0.05). Postoperative CT showed that 53 cases (94.64%) of coracoid bone masses were centered placed vertically, 2 cases (3.57%) were superior, and 1 case (1.79%) was inferior; 49 cases (87.50%) of the coracoid bone grafts were flush with the glenoid, 2 cases (3.57%) and 5 cases (8.93%) were medially and laterally positioned. The volume of coracoid bone graft decreased first and then increased, and the shape of the bone graft was continuously remodeling and gradually matched with the track of the humerus head (the optimal circle of the glenoid), all coracoid bone grafts healed. At last follow-up, the coverage rate of optimal glenoid circle was 89.6%-100%, with an average of 97.4%. The area of glenoid defect was 2.6%±1.3%, which significantly decreased when compared with preoperative (22.4%±5.4%) ( P<0.05). At last follow-up, no obvious degenerative changes of shoulder joint was observed. Conclusion:LU-tarjet procedure for recurrent anterior shoulder dislocation has good mid-term effectiveness with short operation time and few complications.

Purpose: The present study aimed to evaluate the functional outcomes of hip arthroscopy using a noninterportal capsulotomy technique to address labral tears in patients with borderline hip dysplasia (BHD). Additionally, we also compared these outcomes with those of patients with BHD who underwent the standard repaired interportal capsulotomy (RIPC) arthroscopy. Methods: Data from patients with BHD were retrieved from a database of patients who underwent arthroscopic hip surgery with noninterportal capsulotomy or RIPC to treat labral tears between January 2014 and December 2020. Data collected included both pre- and postoperative patient-reported outcomes (PROs). Results: A total of 58 patients (noninterportal capsulotomy, n = 37; RIPC, n = 21) with a mean age of 30.9 +/- 5.6 and 28.6 +/- 5.5 years, respectively, met the inclusion criteria. All of the patients underwent a minimal 2-year follow-up. The mean lateral centreedge angle was 23.3 +/- 1.2 degrees in the noninterportal capsulotomy group and 23.7 +/- 1.0 degrees in the RIPC group, with no significant difference. The PROs improved from the preoperative to the latest follow-up, with a p < 0.001. There were no differences between the groups. Conclusion: Using strict patient selection criteria, hip arthroscopy with noninterportal capsulotomy demonstrated significant pre- to postoperative improvements in patients with BHD and achieved results comparable to those from hip arthroscopy with RIPC. Level of EvidenceLevel III.

There are debates in residual end preservation technique in anterior cruciate ligament reconstruction whether it would promote the bone-tendon healing, knee proprioception recovery, vascularization of synovial membrane and transplanted ligament. This article retrieved the literatures from January 2018 to September 2022, and provided induction, summary and discussion of the influence of residual preservation in anterior cruciate ligament reconstruction on bone tunnel, proprioception recovery, vascularization of synovial membrane and transplanted ligament, and early knee function recovery. Preservation residual anterior cruciate ligament reconstruction shows advantages in promoting early tendon bone healing and vascularization of synovial membrane and transplanted ligament, and is also conducive to the recovery of proprioception, which in turn accelerate the knee joint function recovery. Clinical doctors should base on the residual type of the anterior cruciate ligament rupture in patients, for patients who meet the conditions of residual reserves, surgeons shall retaine the tissue as far as possible during anterior cruciate ligament reconstruction.

Osteoporosis (OP) affects millions worldwide but currently cannot be cured. Suppressing the level of miR-214 in osteoclasts by the anti-miRNA oligonucleotide (AMO) anti-miR-214 reverses bone absorption and provides a potential treatment. Here we report a peptide-guided delivery strategy using red blood cell extracellular vesicles (RBCEVs) as the vehicle to realize osteoclast-targeted delivery of anti-miR-214. A bi-functional peptide, TBP-CP05, which binds to both the CD63 on RBCEVs and receptors on osteoclasts, acts as the guide. TBP-CP05 binds with RBCEVs through CP05, displays the TRAP-binding peptide (TBP) on the surface of EVs, and endows RBCEVs with osteoclast-targeting capability both in vitro and in vivo. Intravenous injection of the osteoclast-targeting RBCEVs (OT-RBCEVs) led to the enrichment of EVs in the bone skeleton, significant inhibition of the osteoclast activity, elevated osteoblast activity, and improved bone density in osteoporotic mice. Altogether, this work demonstrates efficient guidance of drug-loaded EVs to the targeted cells in vivo using bi-functional fusion peptides, and showcases that targeted delivery of anti-miR-214 by OT-RBCEVs may be a viable method for OP treatment. SIGNIFICANCE STATEMENT. Surface functionalization of EVs endows these nanovesicles cell-specific targeting property which guides the drug cargos to specific tissues and cells with higher accuracy, longer retention, and minimal off-target effects. Methods to functionalize EVs with minimal procedures are highly desired for clinical applications. Here we present a facile method using a bifunctional fusion peptide to guide RBCEVs to osteoclasts. A simple incubation of the bifunctional peptide and RBCEVs results in osteoclast-targeting RBCEVs (OT-RBCEVs) that effectively deliver anti-miR-214 to osteoclasts in vivo in a mouse model of osteoporosis, bringing a potential therapy to osteoporotic patients. This is, to our knowledge, the first report on peptide functionalization of RBCEVs and osteoclast-targeted delivery using RBCEVs.

Genome editing technology has emerged as a potential therapeutic tool for treating incurable diseases. In particular, the discovery of clustered regularly interspaced short palindromic repeats (CRISPR)/Cas systems and the design of single-guide RNAs (sgRNAs) have revolutionized genome editing applications. Unfortunately, compared with the rapid development of gene-editing tools, the progress in the development of delivery technologies is lagging behind and thus limiting the clinical application of genome editing. To overcome these limitations, researchers have investigated various delivery systems, including viral and non-viral vectors for delivering CRISPR/Cas and sgRNA complexes. As natural endogenous nanocarriers, extracellular vesicles (EVs) present advantages of biocompatibility, low immunogenicity, stability, and high permeability, making them one of the most promising drug delivery vehicles. This review provides an overview of the fundamental mechanisms of EVs from the aspects of biogenesis, trafficking, cargo delivery, and function as nanotherapeutic agents. We also summarize the latest trends in EV-based CRISPR/Cas delivery systems and discuss the prospects for future development. In particular, we put our emphasis on the state-of-the-art engineering strategies to realize efficient cargo packaging and loading. Altogether, EVs hold promise in bridging genome editing in the laboratory and clinical applications of gene therapies by providing a safe, effective, and targeted delivery vehicle.

Rationale: A cell-specific delivery vehicle is required to achieve gene editing of the disease-associated cells, so the hereditable genome editing reactions are confined within these cells without affecting healthy cells. A hybrid exosome-based nano-sized delivery vehicle derived by fusion of engineered exosomes and liposomes will be able to encapsulate and deliver CRISPR/Cas9 plasmids selectively to chondrocytes embedded in articular cartilage and attenuate the condition of cartilage damage. Methods: Chondrocyte-targeting exosomes (CAP-Exo) were constructed by genetically fusing a chondrocyte affinity peptide (CAP) at the N-terminus of the exosomal surface protein Lamp2b. Membrane fusion of the CAP-Exo with liposomes formed hybrid CAP-exosomes (hybrid CAP-Exo) which were used to encapsulate CRISPR/Cas9 plasmids. By intra-articular (IA) administration, hybrid CAP-Exo/Cas9 sgMMP-13 entered the chondrocytes of rats with cartilage damages that mimicked the condition of osteoarthritis. Results: The hybrid CAP-Exo entered the deep region of the cartilage matrix in arthritic rats on IA administration, delivered the plasmid Cas9 sgMMP-13 to chondrocytes, knocked down the matrix metalloproteinase 13 (MMP-13), efficiently ablated the expression of MMP-13 in chondrocytes, and attenuated the hydrolytic degradation of the extracellular matrix proteins in the cartilage. Conclusion: Chondrocyte-specific knockdown of MMP-13 mitigates or prevents cartilage degradation in arthritic rats, showing that hybrid CAP-Exo/Cas9 sgMMP-13 may alleviate osteoarthritis.

Exosomes secreted by mesenchymal stem cells (MSCs) have been suggested as promising candidates for cartilage injuries and osteoarthritis treatment. Exosomes for clinical application require large-scale production. To this aim, human synovial fluid MSCs (hSF-MSCs) were grown on microcarrier beads, and then cultured in a dynamic three-dimension (3D) culture system. Through utilizing 3D dynamic culture, this protocol successfully obtained large-scale exosomes from SF-MSC culture supernatants. Exosomes were harvested by ultracentrifugation and verified by a transmission electron microscope, nanoparticle transmission assay, and western blotting. Also, the microbiological safety of exosomes was detected. Results of exosome detection suggest that this approach can produce a large number of good manufacturing practices (GMP)-grade exosomes. These exosomes could be utilized in exosome biology research and clinical osteoarthritis treatment.

There is no efficient tracking system available for the therapeutic molecules delivered to cartilage. The dense matrix covering the cartilage surface is the main biological barrier that the therapeutic molecules must overcome. In this study, we aimed to establish a system that can dynamically and effectively track the therapeutic molecules delivered to cartilage. To this aim, we adopted bovine and human cartilage explants as ex vivo models for chondrocyte-targeted exosome dispersion. The efficiency of drug delivery was evaluated using frozen sections. The results of this study showed that the penetration and distribution of chondrocyte-targeted exosomes in cartilage explants can be tracked dynamically. Thus, ex vivo cartilage explants provide an effective and economic system to evaluate therapeutic drugs encapsulated in chondrocyte-targeted exosomes in preclinical studies.

目的 建立猪关节软骨外植体模型,为药物递送修复骨关节炎关节软骨病损的作用提供一种简单经济的研究策略.方法 体外无菌解剖分离猪膝关节软骨,使用活检组织穿孔器取直径为40 mm的小圆柱体.用无血清培养基培养外植体,荧光标记的Rhodamine B-Kartogenin(KGN)进行小分子药物渗透测试.药物渗透试验12 h、24 h、48 h,每个时间点设置3个重复组,获取外植体进行冰冻切片,利用激光共聚焦显微镜观察外植体的结构及其体外培养系统中小分子药物在软骨层的渗透情况,通过Image J分析荧光强度.结果 激光共聚焦显微镜观察,软骨外植体无血清培养模型在体外12 h、24 h、48 h均可维持正常的形态结构,小分子药物Rhodamine B-KGN呈红色荧光,48 h组荧光信号明显增强(P＜0.01),随着时间的推移,药物不断渗入软骨外植体,进入外植体的药物逐渐增多.结论 本研究建立一种猪软骨外植体模型,检测了小分子化合物KGN在软骨外植体中的渗透分布情况,为探讨药物递送对骨关节炎软骨病损的修复作用提供一个简单经济的评价模型.

Objective To investigate the clinical and radiographic short‐term results of arthroscopic treatment for posterior labrum tears with an attached bony fragment after traumatic posterior hip dislocation. Methods Between July 2014 and May 2019, a consecutive series of nine patients diagnosed with a posterior labrum tear with an attached bony fragment after traumatic posterior hip dislocation were treated by hip arthroscopic techniques. The patients had been injured in traffic accidents (n = 6) or high falls (n = 3). All patients were provided primary treatment at the emergency department of our institution, and then were transferred to our department for arthroscopy. Demographic data (e.g. gender, age, etc), intraoperative findings, the preoperative and postoperative multiple clinical scores and radiological results were subsequently assessed. Visual analogue scale for pain (VAS) and modified Harris hip scores (mHHSs) were measured and compared before surgery, and at the last follow‐up. Results A total of nine patients were enrolled, all of them were male, with a mean age at surgery of 32.2 ± 5.6 years (range, 22–65 years). The patients were followed‐up for an average of 26.5 ± 4.1 (range, 24 to 50 years). During the arthroscopic surgery, all patients had labral tears with posterior acetabular rim fracture. All patients had loose osteochondral fragments. Five had partial or complete tears of ligamentum teres. Two patients had osteochondral damage. Two had capsular rupture. Postoperative X‐ray films and three dimension computed tomography (3D‐CT) showed satisfactory reduction of posterior acetabular wall fractures. The mHHS before surgery and at 1 year and 2 years after surgery were 51.8 ± 4.3, 81.8 ± 2.0 and 87.5 ± 1.9 respectively; VAS scores were 5.6 ± 0.5, 1.3 ± 0.3 and 0.7 ± 0.3 respectively. As compared with the condition before surgery, there was a significant improvement in the mHHS and VAS scores at 1 year and 2 years after surgery (P < 0.01). There was no significant improvement in the mHHS and VAS scores between 1 year and 2 years after surgery (P < 0.05). At the final follow‐up, all patients had regained full range of motion (ROM) and were satisfied with the results. None of the patients showed signs of heterotopic ossification, avascular necrosis or progression of osteoarthritis of the hip joint. Conclusion Traumatic dislocation is accompanied by a variety of intra‐articular hip joint pathologies. Managing posterior acetabular rim fracture after traumatic posterior hip dislocation using arthroscopic reduction and fixation with anchors is a safe and minimally invasive option and delays the progression of traumatic osteoarthritis.

目的:探讨双侧股骨髋臼综合征(B-FAI)的临床特点和关节镜治疗效果.方法:回顾性分析2015年5月至2017年5月进行分期两次髋关节镜手术治疗的18例B-FAI患者,记录并比较手术前后双侧髋关节的影像学指标、临床症状和关节镜下病理表现,以及术前与末次随访时疼痛视觉模拟量表(VAS)评分和改良髋关节Harris评分(mHHS).结果:本组18例患者第一次手术和第二手术时间间隔为3～14个月,平均(6.2±4.5)个月.术后随访8～24个月,平均随访时间(8.0±2.5)个月.术前两侧髋关节α角、外侧CE角(LCE)差异均无统计学意义(P均>0.05).第一次手术侧髋关节SeldesⅠ型盂唇撕裂、Ⅱ级盂唇-软骨移行区损伤(ALAD)、OutbridgeⅡ度软骨损伤的比例要高于第二次手术侧髋关节,且差异均有统计学意义(P均<0.05);而两侧髋关节FAI类型、盂唇缝合及关节囊缝合的比例差异均无统计学意义(P均>0.05).与术前相比,末次随访时两侧髋关节VAS评分均降低、mHHS评分均增高,且差异均有统计学意义(P均<0.01);而末次随访时两侧髋关节VAS评分、mHHS评分差异均无统计学意义(P均>0.05).结论:FAI常常累及双侧髋关节,临床中应该常规进行双侧髋关节评估.B-FAI两侧髋关节影像学指标与髋关节的病理损伤相似.分期两次髋关节镜手术治疗B-FAI短期临床效果满意,建议两次手术的合理间隔为3～6个月.

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Proteolytic targeting chimeras (PROTACs) is a rapid and reversible chemical knockout method. Compared with traditional gene-editing tools, it can avoid potential genetic compensation, misunderstandings caused by spontaneous mutations, or gene knockouts that lead to embryonic death. To study the role of estrogen receptor alpha (ERα) in the occurrence and progression of menopausal arthritis, we report a chemical knockout strategy in which stable peptide-based (PROTACs) against ERα to inhibit their function. This chemical knockdown strategy can effectively and quickly inhibit ERα protein in vivo and in vitro. In the rat menopausal arthritis model, this study showed that inhibiting estrogen function by degrading ERα can significantly interfere with cartilage matrix metabolism and cause menopausal arthritis by up-regulating matrix metalloproteinase (MMP-13). The results of this study indicate that ERα is a crucial estrogen receptor for maintaining cartilage metabolism. Inhibition of ERα function by PROTACs can promote the progression of osteoarthritis.

OBJECTIVE:To compare the clinical outcomes and complications of hip arthroscopic treatment for femoroacetabular impingement (FAI) performed with either Inside-out or Outside-in approach.METHODS:The clinical date of 48 patients with FAI treated by hip arthroscopy surgery and follow-up from June 2016 to June 2019 were retrospectively analyzed. According to the different operative methods, the patients were divided into two groups. Inside-out group, from central compartment to peripheral compartment;Outside-in group, from peripheral compartment to central compartment. There were 14 males and 10 females in Inside-out group with an averageage of (39.8±7.6)years old, 13 males and 11 females in Inside-out group with an average age of (39.5±9.1)years old in Outside-in group. There was no significant difference in age, gender, body mass index, side, impingement type, medical history and follow-up time between the two groups. The complication occurrence rate, modified Harris hip score (mHHS)and nonarthritic hip score (NAHS) were compared between these two groups.RESULTS:The mHHs and NAHS scores of the two groups were significantly higher than those before operation, but there was no significant difference between the two groups (P>0.05). In the Inside-out group, there were 4 cases of nerve traction injury and 3 cases of iatrogenic injury, while only 1 case of nerve traction injury occurred in the Outside-in group. The incidence of complications in the inside out group was higher than that in the outside in group (16.7% vs 4.2%, χ2=5.400, P=0.020).CONCLUSION:Both hip arthroscopic surgery methods can obtain satisfactory clinical efficacy in the treatment of FAI, but the incidence of postoperative complications of Outside-in surgical method is lower. The out-side in method can be preferentially selected for the patients with the indications of operation.

Background: Achieving secure fixation and preventing retear have been recognized as fundamental in arthroscopic repair of rotator cuff tears. Moreover, reducing internal implantation can lower medical expenses and minimize the operation time, which is essential for the surgical safety and postoperative rehabilitation of the patients. We have recently proposed the point union bridge (PUB) suture configuration as a novel method for not only providing equivalent fixation but also decreasing the operation time and medical expenses. However, no comparative clinical studies have been performed. Methods: From March 2014 to September 2016, a total of 88 patients with diagnoses of medium-size rotator cuff tears underwent arthroscopic repair with a randomly assigned technique-either the PUB technique (n = 42) or the double-row suture bridge (DRSB) technique (n = 46). All patients underwent a minimal 2-year follow-up. We used the Constant-Murley score (CMS), American Shoulder and Elbow Surgeons (ASES) score, active and passive range of motion, and visual pain-simulation score (visual analog scale [VAS] score) to assess the functional outcomes. In addition, we recorded the arthroscopic operation time, medical costs, and postoperative complications. All patients received magnetic resonance imaging at the 6-month and 2-year postoperative evaluations to assess structural integrity and tendon healing. Results: At the 2-year follow-up, all scoring parameters evaluated (CMS, ASES score, and VAS score), as well as active and passive range of motion, improved significantly in both groups as compared with preoperative assessments. The PUB technique significantly decreased the operation time (55.9 +/- 14.1 minutes vs. 72.2 +/- 14.2 minutes for PUB vs. DRSB, P < .001) and medical expenses ($2608.0 +/- $391.1 vs. $4056.9 +/- $350.9 for PUB vs. DRSB, P < .001 ). However, no significant differences between the 2 techniques were found in any functional assessments of the shoulder (CMS, ASES score, and VAS score), repair integrity, or the retear rate at the 2-year follow-up. Conclusion: Arthroscopic repair of the medium-size rotator cuff tear with either the PUB or DRSB technique could yield both satisfactory improvements in the shoulder function of patients and equivalent tendon integrity. With less consumption of internal implants, the PUB technique significantly reduced the operation time and decreased medical expenses. (C) 2021 Journal of Shoulder and Elbow Surgery Board of Trustees. All rights reserved.

Background: Graft impingement is one of the main concerns in double-bundle anterior cruciate ligament reconstruction (DB-ACLR). Impingement between the anteromedial (AM) and posterolateral (PL) bundles has been postulated to cause graft deterioration or rerupture, but this has not been thoroughly investigated, and the interbundle impingement pressure (IIP) has not been well researched. Purpose: To determine the IIP between the AM and PL bundles in the native anterior cruciate ligament (ACL) and in DB-ACLR with individualized and nonindividualized double-tunnel placement. Study Design: Controlled laboratory study. Methods: A total of 30 fresh-frozen, nonpaired, human cadaveric knees were randomly divided into 3 groups of 10 knees: native intact ACL (NI group), DB-ACLR tunnel placement using the preserved remnant procedure (individualized reconstruction) (PR group), and DB-ACLR tunnel placement using the bony landmark procedure (nonindividualized reconstruction) (BL group). Pressure sensors were inserted between the AM and PL bundles. The knee was moved passively from full extension to full flexion, and the IIP between the 2 ACL bundles was measured every 15°. Similarly, the impingement pressure was measured between the ACL and intercondylar roof and between the ACL and posterior cruciate ligament (PCL). Results: No significant differences were found in the maximum, mean, or minimum ACL-roof and ACL-PCL impingement pressures among the 3 groups. The IIP significantly increased when the knee joint was flexed >120° in all 3 groups ( P < .001). Compared with the other 2 groups, the BL group had significantly higher maximum and mean IIP throughout the range of knee movement ( P < .001) and from maximum extension to 120° of flexion ( P < .001). The BL group also had significantly higher minimum IIP than the other 2 groups when knee flexion was >120° ( P < .001). No significant differences were seen in maximum, minimum, or mean IIP between the NI and PR groups. Conclusion: The PR procedure (individualized DB-ACLR) was more consistent with the interbundle biomechanical conditions of the native ACL, whereas the BL procedure (nonindividualized DB-ACLR) had higher maximum and mean IIP. The IIP was higher than the ACL–intercondylar roof or ACL-PCL pressures, and it increased significantly when knee flexion was >120°. Clinical Relevance: These data suggest that surgeons can perform individualized DB-ACLR using preserved remnants for tunnel placement as impingement-free DB-ACLR.

Transplantation of synovial fluid-derived mesenchymal stem cells (SF-MSCs) is a viable therapy for cartilage degeneration of osteoarthritis (OA). But controlling chondrogenic differentiation of the transplanted SF-MSCs in the joints remains a challenge. Kartogenin (KGN) is a small molecule that has been discovered to induce differentiation of SF-MSCs to chondrocytes both in vitro and in vivo. The clinical application of KGN however is limited by its low water solubility. KGN forms precipitates in the cell, resulting in low effective concentration and thus limiting its chondrogesis-promoting activity. Here we report that targeted delivery of KGN to SF-MSCs by engineered exosomes leads to even dispersion of KGN in the cytosol, increases its effective concentration in the cell, and strongly promotes the chondrogenesis of SF-MSCs in vitro and in vivo. Fusing an MSC-binding peptide E7 with the exosomal membrane protein Lamp 2b yields exosomes with E7 peptide displayed on the surface (E7-Exo) that has SF-MSC targeting capability. KGN delivered by E7-Exo efficiently enters SF-MSCs and induces higher degree of cartilage differentiation than KGN alone or KGN delivered by exosomes without E7. Co-administration of SF-MSCs with E7-Exo/KGN in the knee joints via intra-articular injection also shows more pronounced therapeutic effects in a rat OA model than KGN alone or KGN delivered by exosomes without E7. Altogether, transplantation of SF-MSCs with in situ chondrogenesis enabled by E7-Exo delivered KGN holds promise towards as an advanced stem cell therapy for OA.