Despite numerous attempts to engineer cartilage tissue in recent years, significant challenges remain regarding hyaline cartilage regeneration. One main reason is that the overactivated inflammatory response after injury suppresses inherent cartilage regenerative capabilities. Since the arthritic microenvironment is constantly changing during posttraumatic stress, an inflammatory diagnostic logic‐based hydrogel for cartilage regeneration is developed for the first time through cross‐linking of 4‐arm poly(ethylene glycol)‐vinyl sulfone (PEG‐VS) and specific matrix metalloproteinase (MMP) 13‐sensitive peptides. The hydrogel exhibits diagnostic logic to identify the pathological cue MMP13 and accordingly determine drug release kinetics in an inflammatory microenvironment. Additionally, multiphase therapeutic ability is designed to program different cargo release behaviors to match the inflammation‐chondrogenesis cascade for better cartilage regeneration. Here, it is first proposed that MMP13 is a suitable diagnostic biomarker to modulate the inflammatory microenvironment in the early stage of cartilage injury. In vitro and in vivo studies show that the hydrogel has good injectability, on‐demand anti‐inflammation, and immunomodulation capabilities. Ultimately, loaded with multiple therapeutic factors, the hydrogel shows both microenvironmental modulation and chondrogenesis therapeutic ability, resulting in satisfactory hyaline cartilage regeneration. This study provides critical insight into the design and biological mechanism of both diagnostic and therapeutic ability‐based cartilage tissue engineering strategies.

The regeneration and repair of articular cartilage remains a major challenge for clinicians and scientists due to the poor intrinsic healing of this tissue. Since cartilage injuries are often clinically irregular, tissue-engineered scaffolds that can be easily molded to fill cartilage defects of any shape that fit tightly into the host cartilage are needed. In this study, bone marrow mesenchymal stem cell (BMSC) affinity peptide sequence PFSSTKT (PFS)-modified chondrocyte extracellular matrix (ECM) particles combined with GelMA hydrogel were constructed. In vitro experiments showed that the pore size and porosity of the solid-supported composite scaffolds were appropriate and that the scaffolds provided a three-dimensional microenvironment supporting cell adhesion, proliferation and chondrogenic differentiation. In vitro experiments also showed that GelMA/ECM-PFS could regulate the migration of rabbit BMSCs. Two weeks after implantation in vivo, the GelMA/ECM-PFS functional scaffold system promoted the recruitment of endogenous mesenchymal stem cells from the defect site. GelMA/ECM-PFS achieved successful hyaline cartilage repair in rabbits in vivo, while the control treatment mostly resulted in fibrous tissue repair. This combination of endogenous cell recruitment and chondrogenesis is an ideal strategy for repairing irregular cartilage defects.

目的 探讨合并慢性肺部疾病影像学表现的高龄髋部骨折患者的临床特点及手术治疗的安全性.方法 对2019年1月至2021年12月首都医科大学附属北京世纪坛医院关节外科骨肿瘤科收治的高龄(年龄≥80岁)髋部骨折患者148例的临床资料进行回顾性分析.其中男36例,女112例,年龄(86.4±4.6)(80～99)岁.根据入院时肺部X线或CT检查结果,将全部患者分为合并慢性肺部疾病组(简称为肺疾病组,89例)和不合并慢性肺部疾病组(简称无肺疾病组,59例).对两组患者的年龄、性别构成、骨折类型和合并症等基线资料进行比较;对两组患者住院日、围手术期病死率、是否转入ICU治疗以及肺部感染、心肌梗死、心力衰竭、脑梗死、静脉血栓形成、消化道出血和尿路感染等并发症发生情况进行比较.P<0.05为差异有统计学意义.结果 两组患者的年龄、性别构成、骨折类型和合并症等基线数据差异均无统计学意义(均P>0.05),有可比性.肺疾病组患者围手术期肺部感染和尿路感染发病率显著高于无肺疾病组(χ2=5.531,8.275;P=0.019,0.004);两组患者围手术期病死率、住院日和其他并发症差异均无统计学意义(均P>0.05).结论 影像学提示合并慢性肺部疾病的高龄髋部骨折患者围手术期更易发生肺部感染和尿路感染,但围手术期病死率、住院时间及大多数术后并发症发生率无显著升高.

Articular cartilage (AC) injuries often lead to cartilage degeneration and may ultimately result in osteoarthritis (OA) due to the limited self-repair ability. To date, numerous intra-articular delivery systems carrying various therapeutic agents have been developed to improve therapeutic localization and retention, optimize controlled drug release profiles and target different pathological processes. Due to the complex and multifactorial characteristics of cartilage injury pathology and heterogeneity of the cartilage structure deposited within a dense matrix, delivery systems loaded with a single therapeutic agent are hindered from reaching multiple targets in a spatiotemporal matched manner and thus fail to mimic the natural processes of biosynthesis, compromising the goal of full cartilage regeneration. Emerging evidence highlights the importance of sequential delivery strategies targeting multiple pathological processes. In this review, we first summarize the current status and progress achieved in single-drug delivery strategies for the treatment of AC diseases. Subsequently, we focus mainly on advances in multiple drug delivery applications, including sequential release formulations targeting various pathological processes, synergistic targeting of the same pathological process, the spatial distribution in multiple tissues, and heterogeneous regeneration. We hope that this review will inspire the rational design of intra-articular drug delivery systems (DDSs) in the future.

Since articular cartilage lacks blood vessels, nerves, and lymph tissue, its ability to repair itself is limited. Once damaged, it can lead to joint swelling and pain, accelerating the progression of osteoarthritis. Complete regeneration of hyaline cartilage with good mechanical properties remains an elusive goal, despite the many technologies available today. The inflammatory milieu created by cartilage damage is critical for chondrocyte death and hypertrophy, extracellular matrix breakdown, ectopic bone formation, and the progression of cartilage injury to osteoarthritis. In the inflammatory microenvironment, MSCs undergo aberrant differentiation, and chondrocytes begin to convert or dedifferentiate into cells with a fibroblast phenotype, resulting in fibrocartilage with poor mechanical qualities. All of these suggest that inflammatory problems may be a major stumbling block to cartilage repair. To produce a milieu conducive to cartilage regeneration, multi-dimensional management of the joint inflammatory microenvironment in place and time is required. Therefore, it is of great significance to elucidate the immune microenvironment of cartilage repair and regeneration after injury. This review provides a brief overview of:（1）the pathogenesis of cartilage injury（2）immune cells in cartilage injury and repair（3）effects of inflammatory cytokines on cartilage repair;（4）clinical strategies for the treatment of cartilage defects（5）strategies for targeted immunoregulation in cartilage repair and regeneration.

Rotator cuff repair remains a challenge clinically due to the high retear rate after surgical intervention. There is a significant need to develop functional biomaterials facilitating tendon-to-bone integration. In this study, hydroxyapatite (HA) incorporated polylactic acid (PLLA) aligned nanofibrous membranes were fabricated by electrospinning as a low-cost sustainable rotator cuff patch. The morphology, physical, mechanical and in vitro cell assays of the nanofibrous membranes were characterized. The results showed that the nanofibrous membrane maintained a rough surface and weakened hydrophobicity. It has excellent cytocompatibility, and the cells were oriented along the direction of fiber arrangement. What's more, the PLLA-HA nanofibrous membrane could increase the alkaline phosphatase (ALP) expression in rat bone marrow mesenchymal stem cells (BMSCs), indicating that the electrospinning PLLA-HA nanofibrous membrane can better induce the bone formation of rat BMSCs cells. When the mass ratio of PLLA to HA exceeds 3: 1, with the increase of the HA content, the patch showed rising induction ability. The results suggested that electrospinning PLLA-HA nanofibrous membranes are an ideal patch for promoting tendon-bone healing and reducing the secondary tear rate. Furthermore, the use of biodegradable polymers and low-cost preparation methods presented the possibility for commercial production of these nanofibrous membranes.

背景:通过募集内源性干细胞原位再生软骨损伤的治疗策略,是未来软骨组织工程研究的新方向。目的:构建既能募集干细胞又能促进其黏附和增殖,且有利于新生组织成熟的组织工程软骨复合支架。方法:将脱细胞软骨细胞外基质（extracellular matrix,ECM）与甲基丙烯酸酯化明胶（methacrylated gelatin,GelMA）混合配制光敏性生物墨水,利用3D生物打印技术分别制备单纯聚己内酯[poly（?-caprolactone）,PCL]支架、PCL/GelMA/ECM支架。将转化生长因子β3（transforming growth factorβ3,TGF-β3）负载于生物墨水中制备PCL/GelMA/ECM/TGF-β3支架,检测其缓释性能。从形态学、组织学、生物化学、生物力学等角度评价PCL/GelMA/ECM支架的物理化学性质。利用CCK-8法检测PCL/GelMA/ECM支架的细胞毒性。将脂肪间充质干细胞接种于PCL/GelMA/ECM支架上,1,4,7 d后,共聚焦显微镜下观察细胞活性,扫描电镜观察细胞黏附。将PCL/GelMA/ECM支架植入SD大鼠皮下,组织学观察炎性细胞浸润与支架降解。利用Transwell小室实验检测PCL/GelMA/ECM支架、PCL/GelMA/ECM/TGF-β3支架对脂肪间充质干细胞迁移的影响,以单独培养的细胞为阴性对照。结果与结论:（1）PCL/GelMA/ECM支架呈现三维立体多孔网状结构,无细胞成分,含有Ⅱ型胶原和糖胺聚糖等软骨特异性成分,支架弹性模量为（14.24±2.44）MPa;（2）PCL/GelMA/ECM支架无明显的细胞毒性;（3）脂肪间充质干细胞紧密贴附于PCL/GelMA/ECM支架上,细胞活性良好,可分泌细胞外基质;（4）PCL/GelMA/ECM支架植入大鼠皮下1周后有轻度急性炎症反应,3周后炎性反应减轻,并可见逐步支架降解;（5）PCL/GelMA/ECM/TGF-β3支架具有良好的缓释性能,可持续释放TGF-β3达60 d;（6）相对于阴性对照组,PCL/GelMA/ECM支架、PCL/GelMA/ECM/TGF-β3支架均可促进脂肪间充质干细胞的迁移,其中以PCL/GelMA/ECM/TGF-β3支架促迁移作用更显著;（7）结果表明,3D打印PCL/GelMA/ECM/TGF-β3支架可促进脂肪间充质干细胞的增殖、黏附与迁移。

目的 探讨人脐带间充质干细胞(hUC-MSCs)来源的外泌体对兔骨髓干细胞增殖与迁移的影响.方法 分离培养原代人脐带间充质干细胞,鉴定P3代hUC-MSCs表面标记抗原,进行hUC-MSCs三向分化特性鉴定;分离hUC-MSCs来源外泌体并进行鉴定,测定人脐带间充质干细胞外泌体促进骨髓干细胞增殖、迁移的作用.结果 与结论人脐带间充质干细胞来源的外泌体对骨髓干细胞具有促迁移的作用、无促增殖的作用.

Biomaterials play a core role in cartilage repair and regeneration. The success or failure of an implanted biomaterial is largely dependent on host response following implantation. Host response has been considered to be influenced by numerous factors, such as immune components of materials, cytokines and inflammatory agents induced by implants. Both synthetic and native materials involve immune components, which are also termed as immunogenicity. Generally, the innate and adaptive immune system will be activated and various cytokines and inflammatory agents will be consequently released after biomaterials implantation, and further triggers host response to biomaterials. This will guide the constructive remolding process of damaged tissue. Therefore, biomaterial immunogenicity should be given more attention. Further understanding the specific biological mechanisms of host response to biomaterials and the effects of the host-biomaterial interaction may be beneficial to promote cartilage repair and regeneration. In this review, we summarized the characteristics of the host response to implants and the immunomodulatory properties of varied biomaterial. We hope this review will provide scientists with inspiration in cartilage regeneration by controlling immune components of biomaterials and modulating the immune system.

Appropriate biomimetic scaffolds created via 3D bioprinting are promising methods for treating damaged menisci. However, given the unique anatomical structure and complex stress environment of the meniscus, many studies have adopted various techniques to take full advantage of different materials, such as the printing combined with infusion, or electrospining, to chase the biomimetic meniscus, which makes the process complicated to some extent. Some researchers have tried to tackle the challenges only by 3D biopringting, while its alternative materials and models have been constrained. In this study, based on a multilayer biomimetic strategy, we optimized the preparation of meniscus-derived bioink, gelatin methacrylate (GelMA)/meniscal extracellular matrix (MECM), to take printability and cytocompatibility into account together. Subsequently, a customized 3D bioprinting system featuring a dual nozzle + multitemperature printing was used to integrate the advantages of polycaprolactone (PCL) and meniscal fibrocartilage chondrocytes (MFCs)-laden GelMA/MECM bioink to complete the biomimetic meniscal scaffold, which had the best biomimetic features in terms of morphology and components. Furthermore, cell viability, mechanics, biodegradation and tissue formation in vivo were performed to ensure that the scaffold had sufficient feasibility and functionality, thereby providing a reliable basis for its application in tissue engineering.

肩袖损伤是最常见的肌腱损伤之一,主要表现为肩关节疼痛、僵硬和活动受限 [1] 。据统计,在60 ～ 69岁人群中,肩袖损伤发病率可达31%,而在80岁以上人群中预计高达65% [2] 。肩袖撕裂是严重的肩袖损伤,巨大肩袖撕裂是指撕裂范围＞5 cm或者累及≥2条肌腱的撕裂 [3-4] 。修复肩袖的解剖结构是恢复盂肱关节正常生物力学的基础。肩袖撕裂的治疗经历了开放式手术修补、关节镜辅助下小切口修补和全关节镜下修补几个历史阶段。

Animal models play an important role in preclinical studies, especially in tissue engineering scaffolds for cartilage repair, which require large animal models to verify the safety and effectiveness for clinical use. The small ruminant models are most widely used in this field than other large animals because they are cost-effective, easy to raise, not to mention the fact that the aforementioned animal presents similar anatomical features to that of humans. This review discusses the experimental study of tissue engineering scaffolds for knee articular cartilage regeneration in small ruminant models. Firstly, the selection of these scaffold materials and the preparation process in vitro that have been already used in vivo are briefly reviewed. Moreover, the major factors influencing the rational design and the implementation as well as advantages and limitations of small ruminants are also demonstrated. As regards methodology, this paper applies principles and methods followed by most researchers in the process of experimental design and operation of this kind. By summarizing and comparing different therapeutic concepts, this paper offers suggestions aiming to increase the effectiveness of preclinical research using small ruminant models and improve the process of developing corresponding therapies.

Articular cartilage defect repair is a problem that has long plagued clinicians. Although mesenchymal stem cells (MSCs) have the potential to regenerate articular cartilage, they also have many limitations. Recent studies have found that MSC-derived exosomes (MSC-Exos) play an important role in tissue regeneration. The purpose of this study was to verify whether MSC-Exos can enhance the reparative effect of the acellular cartilage extracellular matrix (ACECM) scaffold and to explore the underlying mechanism. The results of in vitro experiments show that human umbilical cord Wharton's jelly MSC-Exos (hWJMSC-Exos) can promote the migration and proliferation of bone marrow-derived MSCs (BMSCs) and the proliferation of chondrocytes. We also found that hWJMSC-Exos can promote the polarization of macrophages toward the M2 phenotype. The results of a rabbit knee osteochondral defect repair model confirmed that hWJMSC-Exos can enhance the effect of the ACECM scaffold and promote osteochondral regeneration. We demonstrated that hWJMSC-Exos can regulate the microenvironment of the articular cavity using a rat knee joint osteochondral defect model. This effect was mainly manifested in promoting the polarization of macrophages toward the M2 phenotype and inhibiting the inflammatory response, which may be a promoting factor for osteochondral regeneration. In addition, microRNA (miRNA) sequencing confirmed that hWJMSC-Exos contain many miRNAs that can promote the regeneration of hyaline cartilage. We further clarified the role of hWJMSC-Exos in osteochondral regeneration through target gene prediction and pathway enrichment analysis. In summary, this study confirms that hWJMSC-Exos can enhance the effect of the ACECM scaffold and promote osteochondral regeneration.

Despite intensive effort was made to regenerate injured meniscus by cell-free strategies through recruiting endogenous stem/progenitor cells, meniscus regeneration remains a great challenge in clinic. In this study, we found decellularized meniscal extracellular matrix (MECM) preserved native meniscal collagen and glycosami-noglycans which could be a good endogenous regeneration guider for stem cells. Moreover, MECM significantly promoted meniscal fibrochondrocytes viability and proliferation, increased the expression of type II collagen and proteoglycans in vitro. Meanwhile, we designed 3D-printed polycaprolactone (PCL) scaffolds which mimic the circumferential and radial collagen orientation in native meniscus. Taken these two advantages together, a micro-structure and micro-environment dually biomimetic cell-free scaffold was manipulated. This cell-free PCL-MECM scaffold displayed superior biocompatibility and yielded favorable biomechanical capacities closely to native meniscus. Strikingly, neo-menisci were regenerated within PCL-MECM scaffolds which were transplanted into knee joints underwent medial meniscectomy in rabbits and sheep models. Histological staining confirmed neo-menisci showed meniscus-like heterogeneous staining. Mankin scores showed PCL-MECM scaffold could protect articular cartilage well, and knee X-ray examination revealed same results. Knee magnetic resonance imaging (MRI) scanning also showed some neo-menisci in PCL-MECM scaffold group. In conclusion, PCL-MECM scaffold appears to optimize meniscus regeneration. This could represent a promising approach worthy of further investigation in preclinical applications.

Cartilage regeneration is a complex physiological process. Synovial macrophages play a critical immunomodulatory role in the acute inflammatory response surrounding joint injury. Due to the contrasting differences and heterogeneity of macrophage, the phenotype of macrophages are the key determinants of the healing response after cartilage injury. Biomaterials derived from extracellular matrix have been used for the repair and reconstruction of a variety of tissues by modulating the host macrophage response. However, the immunomodulatory effect of decellularized cartilage extracellular matrix (ECM) on macrophages has not been elucidated. It is necessary to clarify the immunomodulatory properties of decellularized cartilage matrix (DCM) to guide the design of cartilage regeneration materials. Here, we prepared porcine articular cartilage derived DCM and determined the response of mouse bone marrow-derived macrophages (BMDMs) to the pepsin-solubilized DCM (PDCM) in vitro. Macrophages activated by the PDCM could promote bone marrow-derived mesenchymal stem cells (BMSCs) invasion, migration, proliferation, and chondrogenic differentiation. Then, we verified that early optimization of the immunomodulatory effects of the cell-free DCM scaffold using IL-4 in vivo could achieve good cartilage regeneration in a rat knee osteochondral defect model. Therefore, this decellularized cartilage ECM scaffold combined with accurate and active immunomodulatory strategies provides a new approach for the development of cartilage regeneration materials. STATEMENT OF SIGNIFICANCE: This work reports a decellularized cartilage extracellular matrix (DCM) scaffold combined with an accurate and active immunomodulatory strategy to improve cartilage regeneration. Our findings demonstrated that the pepsin-solubilized DCM (PDCM) activated bone marrow-derived macrophages to polarize to a constructive macrophage phenotype. These polarized macrophages promoted bone marrow-derived mesenchymal stem cell invasion, migration, proliferation, and chondrogenic differentiation. DCM scaffolds combined with early-stage intra-articular injection of IL-4 created a wound-healing microenvironment and improved cartilage regeneration in a rat knee osteochondral defect model.

Articular cartilage (AC) lesions are fairly common but remain an obstacle for clinicians and researchers due to their poor self-healing capacity. Recently, a promising therapy based on the recruitment of autologous mesenchymal stem cells (MSCs) has been developed for the regeneration of full-thickness cartilage defects in the knee joint. In this study, a 3D-bioprinted difunctional scaffold was developed based on aptamer HM69-mediated MSC-specific recruitment and growth factor-enhanced cell chondrogenesis. The aptamer, which can specifically recognize and recruit MSCs, was first chemically conjugated to the decellularized cartilage extracellular matrix and then mixed with gelatin methacrylate to form a photocrosslinkable bioink ready for 3D bioprinting. Together with the growth factor that promoted cell chondrogenic differentiation, the biodegradable polymer poly(ε-caprolactone) was further chosen to impart mechanical strength to the 3D bioprinted constructs. The difunctional scaffold specifically recruited MSCs, provided a favorable microenvironment for cell adhesion and proliferation, promoted chondrogenesis, and thus greatly improved cartilage repair in rabbit full-thickness defects. In conclusion, this study demonstrated that 3D bioprinting of difunctional scaffolds could be a promising strategy for in situ AC regeneration based on aptamer-directed cell recruitment and growth-factor-enhanced cell chondrogenesis.

Background:Rotator cuff injury, also known as rotator cuff tear (RCT) , is a common shoulder joint injury. Currently there is no unified standard for arthroscopic rehabilitation for RCT injury in terms of improving shoulder function, relieving pain and improving quality of life.Objective:To explore the effect of medical care patient integration with enhanced recovery after surgery (ERAS) rehabilitation model on self-efficacy and rehabilitation effect of functional rehabilitation training of affected limbs after shoulder arthroscopy in patients with RCT.Methods:From April 2020 to April 2021, a randomized controlled study with 60 patients was completed, and the follow-up period was 3 months (daily-nursing group: n=29; ERAS rehabilitation group: n=31) . Postoperative rehabilitation of patients in the two groups was carried out by daily nursing regimen and medical-patient integration ERAS protocol, respectively. The clinical effects of the two groups were evaluated by physical examination, self-efficacy for rehabilitation outcome scale (SER) , Constant-Murley scale.Results:Three months after operation, the total scores of exercise self-efficacy, coping self-efficacy and rehabilitation self-efficacy in the two groups at last follow-up were higher than preoperatively, the experimental group was significantly higher than that in the control group (P < 0.05) ; in the score of Constant-Murley scale 1-week and 3-months after surgery, the ERAS rehabilitation group was significantly higher than that in the Daily-nursing group, and the difference was statistically significant (P < 0.05) ; the compliance of functional exercise in the experimental group was significantly higher than that in the control group 3 months after operation (P < 0.05) .Conclusion:The integrated ERAS rehabilitation model of medical care and patients is helpful to improve the self-efficacy level of upper limb rehabilitation training after arthroscopic treatment of rotator cuff injury, enhance the compliance of rehabilitation exercise, and quickly restore the function of affected limbs.

OBJECTIVES:CD49f is expressed on a variety of stem cells and has certain effects on their cytological functions, such as proliferation and differentiation potential. However, whether CD49f is expressed on the surface of adipose tissue-derived mesenchymal stem cells (ADSCs) and its effect on ADSCs has not been clarified. MATERIALS AND METHODS:The effects of in vitro culture passage and inflammatory factor treatment on CD49f expression and the adhesion ability of ADSCs from mice and rats were investigated. CD49f+ cells were selected from rat ADSCs (rADSCs) by magnetic-activated cell sorting (MACS), and the cellular functions of CD49f+ ADSCs and unsorted ADSCs, including their clonogenic, proliferation, adipogenic and osteogenic differentiation, migration and anti-apoptotic capacities, were compared. RESULTS:CD49f expression and the adhesion ability of ADSCs decreased with increasing in vitro culture passage number. TNF-α and IFN-γ treatment decreased CD49f expression but increased the adhesion ability of ADSCs. After CD49f was blocked with an anti-CD49f antibody, the adhesion ability of ADSCs was decreased. No significant difference in clonogenic activity was observed between unsorted ADSCs and CD49f+ ADSCs. CD49f+ ADSCs had greater proliferation, adipogenic and osteogenic differentiation, migration and anti-apoptotic capacities than unsorted ADSCs. CONCLUSION:In the current study, the expression of CD49f on ADSCs was identified for the first time. The expression of CD49f on ADSCs was influenced by in vitro culture passage number and inflammatory factor treatment. Compared with unsorted ADSCs, CD49f + ADSCs exhibited superior cellular functions, thus may have great application value in mesenchymal stem cell (MSC)-based therapies.

Injury of articular cartilage can cause osteoarthritis and seriously affect the physical and mental health of patients. Unfortunately, current surgical treatment techniques that are commonly used in the clinic cannot regenerate articular cartilage. Regenerative medicine involving stem cells has entered a new stage and is considered the most promising way to regenerate articular cartilage. In terms of theories on the mechanism, it was thought that stem cell-mediated articular cartilage regeneration was achieved through the directional differentiation of stem cells into chondrocytes. However, recent evidence has shown that the stem cell secretome plays an important role in biological processes such as the immune response, inflammation regulation, and drug delivery. At the same time, the stem cell secretome can effectively mediate the process of tissue regeneration. This new theory has attributed the therapeutic effect of stem cells to their paracrine effects. The application of stem cells is not limited to exogenous stem cell transplantation. Endogenous stem cell homing and in situ regeneration strategies have received extensive attention. The application of stem cell derivatives, such as conditioned media, extracellular vesicles, and extracellular matrix, is an extension of stem cell paracrine theory. On the other hand, stem cell pretreatment strategies have also shown promising therapeutic effects. This article will systematically review the latest developments in these areas, summarize challenges in articular cartilage regeneration strategies involving stem cells, and describe prospects for future development.

Injuries to articular cartilage (AC) can lead to cartilage degeneration without timely and proper treatments and ultimately results in osteoarthritis. Regenerative medicine and tissue engineering techniques are emerging as promising approaches for AC regeneration and repair. Typically, AC regenerative medicine and tissue engineering can be divided into two categories, cell-based tissue engineering and cell-homing tissue engineering techniques, based on the involvement of seed cells. Although numerous cell-based techniques can regenerate and repair cartilage lesions to some extent, existing strategies are still restricted by limited cell sources, excessive costs, risks of disease transmission and complex manufacturing practices. However, cell-homing tissue engineering strategies avoid these drawbacks and offer great promise for in situ AC regeneration. These strategies rely on the recruitment of endogenous stem/progenitor cells, host tissue stimulation, and functional responses and thus can provide new insights into in situ cartilage regeneration. This review provides a brief overview of the status of cell-homing tissue engineering strategies; the subpopulations, distribution and migration routes of native joint-resident stem/progenitor cells for regenerating cartilage; chemoattractants that induce enhanced endogenous cell homing; and drug delivery systems and biofunctionalized scaffolds that are indispensable for facilitating in situ AC regeneration and repair.