Increasing attention has been paid to the development of effective strategies for articular cartilage (AC) and osteochondral (OC) regeneration due to their limited self-reparative capacities and the shortage of timely and appropriate clinical treatments. Traditional cell-dependent tissue engineering faces various challenges such as restricted cell sources, phenotypic alterations, and immune rejection. In contrast, endogenous tissue engineering represents a promising alternative, leveraging acellular biomaterials to guide endogenous cells to the injury site and stimulate their intrinsic regenerative potential. This review provides a comprehensive overview of recent advancements in endogenous tissue engineering strategies for AC and OC regeneration, with a focus on the tissue engineering triad comprising endogenous stem/progenitor cells (ESPCs), scaffolds, and biomolecules. Multiple types of ESPCs present within the AC and OC microenvironment, including bone marrow-derived mesenchymal stem cells (BMSCs), adipose-derived mesenchymal stem cells (AD-MSCs), synovial membrane-derived mesenchymal stem cells (SM-MSCs), and AC-derived stem/progenitor cells (CSPCs), exhibit the ability to migrate toward injury sites and demonstrate pro-regenerative properties. The fabrication and characteristics of scaffolds in various formats including hydrogels, porous sponges, electrospun fibers, particles, films, multilayer scaffolds, bioceramics, and bioglass, highlighting their suitability for AC and OC repair, are systemically summarized. Furthermore, the review emphasizes the pivotal role of biomolecules in facilitating ESPCs migration, adhesion, chondrogenesis, osteogenesis, as well as regulating inflammation, aging, and hypertrophy-critical processes for endogenous AC and OC regeneration. Insights into the applications of endogenous tissue engineering strategies for in vivo AC and OC regeneration are provided along with a discussion on future perspectives to enhance regenerative outcomes.

Tissue engineering is theoretically considered a promising approach for repairing osteochondral defects. Nevertheless, the insufficient osseous support and integration of the cartilage layer and the subchondral bone frequently lead to the failure of osteochondral repair. Drawing from this, it was proposed that incorporating glycine-modified attapulgite (GATP) into poly(1,8-octanediol-co-citrate) (POC) scaffolds via the one-step chemical cross-linking is proposed to enhance cartilage and subchondral bone defect repair simultaneously. The effects of the GATP incorporation ratio on the physicochemical properties, chondrocyte and MC3T3-E1 behavior, and osteochondral defect repair of the POC scaffold were also evaluated. In vitro studies indicated that the POC/10% GATP scaffold improved cell proliferation and adhesion, maintained cell phenotype, and upregulated chondrogenesis and osteogenesis gene expression. Animal studies suggested that the POC/10% GATP scaffold has significant repair effects on both cartilage and subchondral bone defects. Therefore, the GATP-incorporated scaffold system with dual-lineage bioactivity showed potential application in osteochondral regeneration.

OBJECTIVE: The present study aimed to compare the clinical outcomes and safety at a 1-year follow-up after 5 or 6 weeks of non-weight bearing after a Talar OsteoPeriostic grafting from the Iliac Crest (TOPIC) for a medial osteochondral lesion of the talus (OLT).
METHODS: A retrospective comparative case-control analysis of prospectively followed patients who underwent a TOPIC procedure with medial malleolus osteotomy was performed. Patients were matched in two groups with either 5 or 6 weeks of non-weight bearing. Clinical outcomes were evaluated using the Numeric Rating Scale (NRS) during walking, rest, running, and stairclimbing. Additionally, the Foot and Ankle Outcome Score (FAOS) and American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot score were assessed. Moreover, radiology and complications were assessed.
RESULTS: Eleven patients were included in the 5-week non-weight bearing group and 22 in the 6-week non-weight bearing group. No significant differences were found in any of the baseline variables. The NRS during walking in the 5-week group improved by 3.5 points and 4 points for the 6-week group (p = 0.58 at 1-year post-operatively). In addition, all other NRS scores, FAOS subscales and the AOFAS scores improved (all n.s. at 1 year follow-up). No significant differences in radiological (osteotomy union and cyst presence in the graft) were found. Moreover, no significant differences were found in terms of complications and reoperations.
CONCLUSIONS: No statistical significant differences were found in terms of clinical, radiological and safety outcomes between 5 or 6 weeks of non-weight bearing following a TOPIC for a medial OLT.
METHODS: Level III, Therapeutic.

UNASSIGNED: Multilayered osteochondral scaffolds are becoming increasingly utilized for the repair of knee joint surface lesions (KJSLs). However, the literature on predictive factors is rather limited.
UNASSIGNED: To (1) evaluate the clinical outcomes and safety of a combined single-step approach using a biomimetic collagen-hydroxyapatite scaffold (CHAS) and filtered bone marrow aspirate (fBMA) for the treatment of KJSLs and (2) identify significant predictors of the treatment outcomes.
UNASSIGNED: Case series; Level of evidence, 4.
UNASSIGNED: All patients who underwent surgery because of a KJSL (size ≥1.5 cm2; International Cartilage Regeneration & Joint Preservation Society grades 3-4) using the combination above were selected from a hospital registry database (100 patients; minimum 2-year follow-up). Patient characteristics, medical history, knee joint and lesion status, intraoperative details, and cellular parameters of the injected fBMA were collected. The arthroscopic evaluation of chondral and meniscal tissue quality in all knee compartments was performed using the Chondropenia Severity Score. Treatment outcomes were determined clinically using patient-reported outcome measures (Knee Injury and Osteoarthritis Outcome Score, EuroQol-5 Dimensions-3 Levels, EuroQol-Visual Analog Scale, and Tegner Activity Scale) and by assessing the occurrence of serious adverse events and graft failure. Multivariable regression analysis was performed to identify significant predictors of the treatment outcomes.
UNASSIGNED: At a mean follow-up of 54.2 ± 19.4 months, 78 (87%) patients completed the questionnaires with significant improvements toward the baseline (P < .00625): KOOS Pain subscale from 62 ± 17 to 79 ± 18, KOOS Total score from 57 ± 16 to 70 ± 20, EuroQol-Visual Analog Scale from 61 ± 21 to 76 ± 16, EuroQol-5 Dimensions-3 Levels from 0.57 ± 0.20 to 0.80 ± 0.21, and Tegner Activity Scale from 2.8 ± 1.5 to 3.9 ± 1.9. The graft failure rate was 4%. A longer duration of preoperative symptoms, previous surgery, larger lesions, older age, and female sex were the main negative predictors for the treatment outcomes. The Chondropenia Severity Score and the number of fibroblast colony-forming units in fBMA positively influenced some of the clinical results and safety.
UNASSIGNED: A CHAS augmented with fBMA proved to be an adequate and safe approach for the treatment of KJSLs up to midterm follow-up. Based on the subanalysis of predictive factors, the surgical intervention should be performed in a timely and precise manner to prevent lesion enlargement, deterioration of the general knee cartilage status, and recurrent surgical procedures, especially in older and female patients. When a CHAS is used, the quantity of MSCs seems to play a role in augmentation.
UNASSIGNED: NCT06078072 (ClinicalTrials.gov identifier).

UNASSIGNED: The etiology and pathogenesis of osteochondritis dissecans (OCDs) lesions remain controversial.
UNASSIGNED: This review presents the recent evolution about the healing, imaging, pathogenesis, and how to treat OCD of the capitellum in overhead athletes.
UNASSIGNED: Compressive and shear forces to the growing capitellum can cause subchondral separation, leading to OCD, composed of 3 layers: articular fragment, gap, and underlying bone. Subchondral separation can cause ossification arrest (stage IA), followed by cartilage degeneration (stage IB) or delayed ossification (stage IIA), occasionally leading to osteonecrosis (stage IIB) in the articular fragment. Articular cartilage fracture and gap reseparation make the articular fragment unstable. The mean tilting angle of capitellar OCD is 57.6 degrees in throwers. Anteroposterior radiography of the elbow at 45 degrees of flexion (APR45) can increase the diagnostic reliability, showing OCD healing stages, as follows: I) radiolucency, II) delayed ossification, and III) union. Coronal computed tomography and magnetic resonance imaging with an appropriate tilting angle can also increase the reliability. MRI is most useful to show the instability, although it occasionally underestimates. Sonography contributes to detection of early OCD in adolescent throwers on the field. OCD lesions in the central aspect of the capitellum can be more unstable and may not heal. Cast immobilization has a positive effect on healing for stable lesions. Arthroscopic removal provides early return to sports, although a large osteochondral defect is associated with a poor prognosis. Fragment fixation, osteochondral autograft transplantation, and their hybrid technique have provided better results.
UNASSIGNED: Further studies are needed to prevent problematic complications of capitellar OCD, such as osteoarthritis and chondrolysis.

Tissue engineered scaffolds are needed to support physiological loads and emulate the micrometer-scale strain gradients within tissues that guide cell mechanobiological responses. We designed and fabricated micro-truss structures to possess spatially varying geometry and controlled stiffness gradients. Using a custom projection microstereolithography (μSLA) system, using digital light projection (DLP), and photopolymerizable poly(ethylene glycol) diacrylate (PEGDA) hydrogel monomers, three designs with feature sizes < 200 μm were formed: (1) uniform structure with 1 MPa structural modulus ( E ) designed to match equilibrium modulus of healthy articular cartilage, (2) E  = 1 MPa gradient structure designed to vary strain with depth, and (3) osteochondral bilayer with distinct cartilage ( E  = 1 MPa) and bone ( E  = 7 MPa) layers. Finite element models (FEM) guided design and predicted the local mechanical environment. Empty trusses and poly(ethylene glycol) norbornene hydrogel-infilled composite trusses were compressed during X-ray microscopy (XRM) imaging to evaluate regional stiffnesses. Our designs achieved target moduli for cartilage and bone while maintaining 68-81% porosity. Combined XRM imaging and compression of empty and hydrogel-infilled micro-truss structures revealed regional stiffnesses that were accurately predicted by FEM. In the infilling hydrogel, FEM demonstrated the stress-shielding effect of reinforcing structures while predicting strain distributions. Composite scaffolds made from stiff μSLA-printed polymers support physiological load levels and enable controlled mechanical property gradients which may improve in vivo outcomes for osteochondral defect tissue regeneration. Advanced 3D imaging and FE analysis provide insights into the local mechanical environment surrounding cells in composite scaffolds.

Osteochondral defects are deep joint surface lesions that affect the articular cartilage and the underlying subchondral bone. In the current study, a tissue engineering approach encompassing individual cells encapsulated in a biocompatible hydrogel is explored in vitro and in vivo. Cell-laden hydrogels containing either human periosteum-derived progenitor cells (PDCs) or human induced pluripotent stem cell (iPSC)-derived chondrocytes encapsulated in gelatin methacryloyl (GelMA) were evaluated for their potential to regenerate the subchondral mineralized bone and the articular cartilage on the joint surface, respectively. PDCs are easily isolated and expanded progenitor cells that are capable of generating mineralized cartilage and bone tissue in vivo via endochondral ossification. iPSC-derived chondrocytes are an unlimited source of stable and highly metabolically active chondrocytes. Cell-laden hydrogel constructs were cultured for up to 28 days in a serum-free chemically defined chondrogenic medium. On day 1 and day 21 of the differentiation period, the cell-laden constructs were implanted subcutaneously in nude mice to evaluate ectopic tissue formation 4 weeks post-implantation. Taken together, the data suggest that iPSC-derived chondrocytes encapsulated in GelMA can generate hyaline cartilage-like tissue constructs with different levels of maturity, while using periosteum-derived cells in the same construct type generates mineralized tissue and cortical bone in vivo. Therefore, the aforementioned cell-laden hydrogels can be an important part of a multi-component strategy for the manufacturing of an osteochondral implant.

OBJECTIVE: To characterize aspects of triiodothyronine (T3) induced chondrocyte terminal maturation within the molecular osteoarthritis pathophysiology using the previously established T3 human ex vivo osteochondral explant model.
METHODS: RNA-sequencing was performed on explant cartilage obtained from OA patients (n = 8), that was cultured ex vivo with or without T3 (10 ng/ml), and main findings were validated using RT-qPCR in an independent sample set (n = 22). Enrichment analysis was used for functional clustering and comparisons with available OA patient RNA-sequencing and GWAS datasets were used to establish relevance for OA pathophysiology by linking to OA patient genomic profiles.
RESULTS: Besides the upregulation of known hypertrophic genes EPAS1 and ANKH, T3 treatment resulted in differential expression of 247 genes with main pathways linked to extracellular matrix and ossification. CCDC80, CDON, ANKH and ATOH8 were among the genes found to consistently mark early, ongoing and terminal maturational OA processes in patients. Furthermore, among the 37 OA risk genes that were significantly affected in cartilage by T3 were COL12A1, TNC, SPARC and PAPPA.
CONCLUSIONS: RNA-sequencing results show that metabolic activation and recuperation of growth plate morphology are induced by T3 in OA chondrocytes, indicating terminal maturation is accelerated. The molecular mechanisms involved in hypertrophy were linked to all stages of OA pathophysiology and will be used to validate disease models for drug testing.

OBJECTIVE: To systematically review the literature and analyze clinical outcomes and return-to-sport after surgical management of cartilage injuries in football players.
METHODS: A systematic literature review was performed in August 2023 on PubMed, WebOfScience, and Cochrane Library to collect studies on surgical strategies for cartilage lesions in football players. Methodological quality and risk of bias were assessed with the modified Coleman Methodology score and RoB2 and RoBANS2 tools.
RESULTS: Fifteen studies on 409 football players (86% men, 14% women) were included: nine prospective and two retrospective case series, one randomized controlled trial, one prospective comparative study, one case report, and one survey. Bone marrow stimulation (BMS) techniques were the most documented. The lesion size influenced the treatment choice: debridement was used for small lesions (1.1 cm2), BMS, osteochondral autograft transplantation (OAT), matrix-assisted autologous chondrocytes transplantation (MACT), and scaffold-augmented BMS for small/mid-size lesions (2.2-3.0 cm2), and autologous chondrocytes implantation (ACI) for larger lesions (5.8 cm2). The surgical options yielded different results in terms of clinical outcome and return-to-sport, with fastest recovery for debridement and scaffold-augmented BMS. The current evidence is limited with large methodological quality variation (modified Coleman Methodology score 43.5/100) and a high risk of bias.
CONCLUSIONS: Decision-making in cartilage injuries seems to privilege early return-to-sport, making debridement and microfractures the most used techniques. The lesion size influences the treatment choice. However, the current evidence is limited. Further studies are needed to confirm these findings and establish a case-based approach to treat cartilage injuries in football players based on the specific patient and lesion characteristics and the treatments\' potential in terms of both return-to-sport and long-term results.
METHODS: Systematic review, level IV.

BACKGROUND: Condylar fractures are a major cause of morbidity and mortality in Thoroughbred racehorses. Condylar fractures have a variety of fracture configurations that suggest there may be differences in aetiopathogenesis.
OBJECTIVE: To determine if exercise history differs with condylar fracture location in a population of Thoroughbred racehorses.
METHODS: Retrospective analysis of clinical and exercise data.
METHODS: Exercise history of Thoroughbred racehorses that had condylar fracture repair between 1 January 2018 and 28 February 2021 was compared between racehorses that had fractures located radiographically either within the parasagittal groove (PSG) or abaxial to the PSG (non-PSG). Age, sex, and last event (race, timed work) matched control groups were compared between the PSG and non-PSG groups. Additionally, exercise history variables of both groups were each compared with a group-specific control population, each consisting of three control racehorses of equivalent age and sex matched to each affected racehorse by last event (race or official timed work) before fracture.
RESULTS: Eighty-two horses with 84 fractures (45 PSG, 39 non-PSG) met inclusion criteria. Age was not different between groups (PSG: 3.4 ± 1.3 years [mean ± SD], non-PSG: 3.7 ± 1.3, p = 0.3). Number of races (PSG: 5.3 ± 7.1, non-PSG: 11.4 ± 8.9, p < 0.001), total race furlongs (PSG: 38.2 ± 54.7, non-PSG: 79.2 ± 64, p = 0.003), and number of active days (PSG: 304 ± 224, non-PSG: 488 ± 314, p = 0.003) before fracture were greater; while mean number of layups was fewer (PSG: 1.0 ± 1.2, non-PSG: 0.5 ± 0.7, p = 0.02) in horses with non-PSG fracture. Horses with non-PSG fracture had more differences compared with their respective control group than horses with PSG fractures. Outcomes following fracture repair were not different between groups.
CONCLUSIONS: Retrospective study, one regional racehorse population, two-dimensional imaging and potential inherent bias for fracture localisation, low statistical power for return to performance analysis.
CONCLUSIONS: Thoroughbred racehorses with non-PSG condylar fractures have a more extensive exercise history than horses with PSG condylar fractures, suggesting differences in fracture aetiopathogenesis.
UNASSIGNED: Fraturas condilares são uma das principais causas de morbidade e mortalidade em cavalos de corrida puro‐sangue inglês. As fraturas condilares apresentam uma variedade de configurações que sugerem que pode haver diferenças em suas etiopatogenia.
OBJECTIVE: Determinar se o histórico de exercícios difere com a localização da fratura condilar em uma população de cavalos de corrida puro‐sangue inglês.
UNASSIGNED: Análise retrospectiva de dados clínicos e de exercício. MÉTODOS: O histórico de exercícios de cavalos de corrida puro‐sangue inglês que tiveram reparo de fratura condilar entre 1 de janeiro de 2018 e 28 de fevereiro de 2021 foi comparado entre cavalos de corrida que tiveram fratura localizada radiograficamente dentro da ranhura parasagital (RPS) ou abaxial à RPS (não RPS). Os grupos foram pareados de acordo com a idade, sexo e último evento (corrida ou trabalho cronometrado) para comparação de RPS e não RPS. Além disso, as variáveis de histórico de exercícios de ambos os grupos foram comparadas a uma população de controle específica, cada uma consistindo em três cavalos de corrida de controle com idade e sexo equivalentes combinados com cada cavalo de corrida afetado pelo último evento (corrida ou trabalho cronometrado oficial) antes da fratura.
RESULTS: Oitenta e dois cavalos com 84 fraturas (45 RPS, 39 não RPS) atenderam aos critérios de inclusão. A idade não foi diferente entre os grupos (RPS: 3,4 ± 1,3 anos (média ± DP), não RPS: 3,7 ± 1,3, p=0,3). O número de corridas (RPS: 5,3 ± 7,1, não RPS: 11,4 ± 8,9, p<0,001), furlongs totais de corrida (RPS: 38,2 ± 54,7, não RPS: 79,2 ± 64, p=0,003) e número de dias ativos (RPS: 304 ± 224, não RPS: 488 ± 314, p=0,003) antes da fratura foram maiores; enquanto o número médio de repousos foi menor (RPS: 1,0 ± 1,2, não RPS: 0,5 ± 0,7, p=0,02) em cavalos com fratura não RPS. Cavalos com fratura não RPS tiveram mais diferenças em comparação com seu grupo controle respectivo do que cavalos com fraturas RPS. Os resultados após o reparo da fratura não foram diferentes entre os grupos. PRINCIPAIS LIMITAÇÕES: Estudo retrospectivo, uma população regional de cavalos de corrida, imagens bidimensionais e viés inerente potencial para localização de fraturas, baixo poder estatístico para análise de retorno ao desempenho. CONCLUSÕES: Cavalos de corrida puro‐sangue inglês com fraturas condilares não RPS têm um histórico de exercícios mais extenso do que cavalos com fraturas condilares RPS, sugerindo diferenças na etiopatogenia das fraturas.