Tibial Tubercle Osteotomy May Not Provide Additional Benefit in Treating Patellar Dislocation With Increased Tibial Tuberosity-Trochlear Groove Distance: A Systematic Review.

PURPOSE: To examine the indications and outcomes of medial patellofemoral ligament reconstruction (MPFLR) with or without tibial tubercle osteotomy (TTO) in treating recurrent or habitual patellar dislocation with an increased tibial tuberosity-trochlear groove (TT-TG) distance. METHODS: We performed a literature search of the established medical databases Cochrane Central, PubMed-MEDLINE, EMBASE, and Web of Science. The inclusion criteria were as follows: skeletally mature patients with recurrent or habitual patellar dislocation and an increased TT-TG distance, treatment with MPFLR combined with a TTO procedure or isolated MPFLR, and reporting of clinical outcomes and complications. Each study was assessed for quality and the level of evidence. The general characteristics, indications, surgical techniques, TT-TG distance, clinical results, imaging evaluation findings, and complications of each study were recorded. RESULTS: Nine studies consisting of 288 knees met the inclusion criteria. The average Coleman score was 71.56 (range, 55-83). The threshold for an increased TT-TG distance ranged from 16 to 20 mm in the included studies. Similar good postoperative outcomes were reported in patients with an increased TT-TG distance treated with MPFLR with versus without a TTO procedure. The mean postoperative Lysholm score ranged from 75.0 to 94.7 (I2 = 87.6%) in the isolated MPFLR group and from 85.0 to 87.6 (I2 = 16.3%) in the TTO-with-MPFLR group. Similar postoperative congruence angles were reported in both groups. The postoperative redislocation rate ranged from 0% to 4.2% in the TTO-with-MPFLR group, and no redislocation was found in the isolated MPFLR group. The postoperative apprehension sign was only reported in isolated MPFLR patients. CONCLUSIONS: The outcomes of MPFLR with or without TTO to treat recurrent or habitual patellar dislocation with an increased TT-TG distance appeared similar. However, this study was limited by the considerable heterogeneity, variety of techniques, variety of TT-TG distances, and variability in patella alta and trochlear dysplasia among the included studies. LEVEL OF EVIDENCE: Level IV, systematic review of Level II to IV studies.

The meniscotibial ligament does exist: An anatomic and histological description.

Purpose: To describe the anatomical and histological characteristics of the human MTL (meniscotibial ligament) that keeps the meniscus stable and are rarely discussed. Study design: Descriptive laboratory study. Methods: In total, six fresh-frozen adult cadaver knees were dissected, and the dissection protocol were designed by two experienced anatomy professors. The anatomical morphology of MTL was observed. The main anatomical specimens included meniscus, tibial plateau, MTL. The osteotome was used to excise the portion of the tibial plateau, which could obtain the complex including partial meniscus, MTL, and a tibial fragment. A histopathologic study was performed by two experienced pathologists. Results: Macroscopically, the MTL could be divided into two parts: medial meniscotibial ligament (MMTL)and lateral meniscotibial ligament (LMTL). The MMTL is distributed continuously, whereas the LMTL is discontinuous on the tibial plateau. The average length from the tibial attachment of the LMTL to the articular surface was 19 ± 1.0mm (mean ± SD). The average length from the tibial attachment of the MMTL to the articular surface was 10 ± 1.2 mm (mean ± SD). Microscopy of the MTL showed that the MTL is a ligamentous tissue, composed of a network of oriented collagenous fibers. Conclusions: In all knees, the MTL was inserted on the outer edge of the meniscus, attaching to the tibia below the level of articular cartilage, which was key to maintaining the rotational stability of knee and the meniscus in the physiological position on the tibial plateau. Histological analysis of this ligament demonstrated that the MTL is a veritable ligamentous structure, which is made up of collagen type I-expressing fibroblasts. Clinical relevance: This article contributes to the understanding of the anatomical and histological characteristics of the MTL. It is beneficial to promote the development of relevant surgical techniques for the MTL lesion.

Comparison of the Clinical Outcomes of Revision and Primary ACL Reconstruction: A Matched-Pair Analysis With 3-5 Years of Follow-up.

BACKGROUND: There are limited studies designed by matching related factors to compare clinical outcomes and return to sport (RTS) between patients undergoing revision anterior cruciate ligament reconstruction (R-ACLR) and primary ACLR (P-ACLR). PURPOSE: (1) To compare the outcomes between R-ACLR and P-ACLR in a matched-pair analysis with 3- to 5-year follow-up and (2) to evaluate patient-reported factors for not returning to preinjury-level sport. STUDY DESIGN: Cohort study; Level of evidence, 4. METHODS: Patients who underwent R-ACLR between September 2016 and November 2018 were propensity matched by age, sex, body mass index, passive anterior tibial subluxation, and generalized hypermobility in a 1:1 ratio to patients who underwent P-ACLR during the same period. By combining in person follow-up at 2 years postoperatively and telemedicine interview at the final follow-up (January 2022), knee stability and clinical scores were compared, including International Knee Documentation Committee (IKDC), Lysholm, and Tegner. Status of RTS was requested, specifically whether the patient returned to preinjury level of sport. Patient-reported reasons for not returning were analyzed. RESULTS: There were 63 matched pairs in the present study. Knee stability was similar in terms of KT-2000 arthrometer, Lachman test, and pivot-shift test results between the groups at 2 years of follow-up. At the final follow-up, no significant difference was found between groups for postoperative clinical scores (IKDC, Tegner, and Lysholm) (P > .05). There was a significant difference in total RTS: 53 (84.1%) in the P-ACLR cohort and 41 (65.1%) in the R-ACLR cohort (P = .014). No significant difference was shown in terms of RTS at the same level: 35 (55.6%) in P-ACLR and 31 (49.2%) in R-ACLR (P = .476). Significantly more patients showed fear of reinjury: 26 of 32 (81.3%) in the R-ACLR group as compared with 15 of 28 (53.5%) in the P-ACLR group (P < .021). CONCLUSION: R-ACLR resulted in similar clinical scores (IKDC, Tegner, and Lysholm) but significantly lower RTS versus P-ACLR at 3 to 5 years of follow-up. Fear of reinjury was the most common factor that caused sport changes in patients with R-ACLR.

An immunomodulatory polypeptide hydrogel for osteochondral defect repair.

Osteochondral injury is a common and frequent orthopedic disease that can lead to more serious degenerative joint disease. Tissue engineering is a promising modality for osteochondral repair, but the implanted scaffolds are often immunogenic and can induce unwanted foreign body reaction (FBR). Here, we prepare a polypept(o)ide-based PAA-RGD hydrogel using a novel thiol/thioester dual-functionalized hyperbranched polypeptide P(EG3Glu-co-Cys) and maleimide-functionalized polysarcosine under biologically benign conditions. The PAA-RGD hydrogel shows suitable biodegradability, excellent biocompatibility, and low immunogenicity, which together lead to optimal performance for osteochondral repair in New Zealand white rabbits even at the early stage of implantation. Further in vitro and in vivo mechanistic studies corroborate the immunomodulatory role of the PAA-RGD hydrogel, which induces minimum FBR responses and a high level of polarization of macrophages into the immunosuppressive M2 subtypes. These findings demonstrate the promising potential of the PAA-RGD hydrogel for osteochondral regeneration and highlight the importance of immunomodulation. The results may inspire the development of PAA-based materials for not only osteochondral defect repair but also various other tissue engineering and bio-implantation applications.

Meniscus heterogeneity and 3D-printed strategies for engineering anisotropic meniscus.

The meniscus is a fibrocartilaginous tissue of the knee joint that plays an important role in load transmission, shock absorption, joint stability maintenance, and contact stress reduction. Mild meniscal injuries can be treated with simple sutures, whereas severe injuries inevitably require meniscectomy. Meniscectomy destroys the mechanical microenvironment of the knee joint, leading to cartilage degeneration and osteoarthritis. Tissue engineering techniques, as a strategy with diverse sources and customizable and adjustable mechanical and biological properties, have emerged as promising approaches for the treatment of meniscal injuries and are represented by 3D printing. Notably, the heterogeneity of the meniscus, including its anatomical structure, cell phenotype, extracellular matrix, and biomechanical properties, is crucial for its normal function. Therefore, the construction of heterogeneous tissue-engineered menisci (TEM) has become a research hotspot in this field. In this review, we systematically summarize the heterogeneity of menisci and 3D-printed strategies for tissue-engineered anisotropic menisci. The manufacturing techniques, biomaterial combinations, surface functionalization, growth factors, and bioreactors related to 3D-printed strategies are introduced and a promising direction for the future research is proposed.

Physical therapy and orthopaedic equipment-induced reduction in the biomechanical risk factors related to knee osteoarthritis: a systematic review and Bayesian network meta-analysis of randomised controlled trials.

OBJECTIVE: Are physical therapy or orthopaedic equipment efficacious in reducing the biomechanical risk factors in people with tibiofemoral osteoarthritis (OA)? Is there a better therapeutic intervention than others to improve these outcomes? DESIGN: Systematic review with network meta-analysis (NMA) of randomised trials. DATA SOURCES: PubMed, Web of Science, Cochrane Library, Embase and MEDLINE were searched through January 2021. ELIGIBILITY CRITERIA FOR SELECTING STUDIES: We included randomised controlled trials exploring the benefits of using physical therapy or orthopaedic equipment in reducing the biomechanical risk factors which included knee adduction moment (KAM) and knee adduction angular impulse (KAAI) in individuals with tibiofemoral OA. DATA EXTRACTION AND SYNTHESIS: Two authors extracted data independently and assessed risk of bias. We conducted an NMA to compare multiple interventions, including both direct and indirect evidences. Heterogeneity was assessed (sensitivity analysis) and quantified (I2 statistic). Grading of Recommendations Assessment, Development and Evaluation assessed the certainty of the evidence. RESULTS: Eighteen randomised controlled trials, including 944 participants, met the inclusion criteria, of which 14 trials could be included in the NMA. Based on the collective probability of being the overall best therapy for reducing the first peak KAM, lateral wedge insoles (LWI) plus knee brace was closely followed by gait retraining, and knee brace only. Although no significant difference was observed among the eight interventions, variable-stiffness shoes and neuromuscular exercise exhibited an increase in the first peak KAM compared with the control condition group. And based on the collective probability of being the overall best therapy for reducing KAAI, gait retraining was followed by LWI only, and lower limb exercise. CONCLUSION: The results of our study support the use of LWI plus knee brace for reducing the first peak KAM. Gait retraining did not rank highest but it influenced both KAM and KAAI and therefore it was the most recommended therapy for reducing the biomechanical risk factors.

Immunomodulatory PEG-CRGD Hydrogels Promote Chondrogenic Differentiation of PBMSCs.

Cartilage damage is a common injury. Currently, tissue engineering scaffolds with composite seed cells have emerged as a promising approach for cartilage repair. Polyethylene glycol (PEG) hydrogels are attractive tissue engineering scaffold materials as they have high water absorption capacity as well as nontoxic and nutrient transport properties. However, PEG is fundamentally bio-inert and lacks intrinsic cell adhesion capability, which is critical for the maintenance of cell function. Cell adhesion peptides are usually added to improve the cell adhesion capability of PEG-based hydrogels. The suitable cell adhesion peptide can not only improve cell adhesion capability, but also promote chondrogenesis and regulate the immune microenvironment. To improve the interactions between cells and PEG hydrogels, we designed cysteine-arginine-glycine-aspartic acid (CRGD), a cell adhesion peptide covalently cross-linked with PEG hydrogels by a Michael addition reaction, and explored the tissue-engineering hydrogels with immunomodulatory effects and promoted chondrogenic differentiation of mesenchymal stem cells (MSCs). The results indicated that CRGD improved the interaction between peripheral blood mesenchymal stem cells (PBMSCs) and PEG hydrogels. PEG hydrogels modified with 1 mM CRGD had the optimal capacity to promote chondrogenic differentiation, and CRGD could induce macrophage polarization towards the M2 phenotype to promote tissue regeneration and repair. PEG-CRGD hydrogels combined with PBMSCs have the potential to be suitable scaffolds for cartilage tissue engineering.

Integrated Analysis of lncRNA and mRNA Expression Profiles Indicates Age-Related Changes in Meniscus.

Little has been known about the role of long non-coding RNA (lncRNA) involves in change of aged meniscus. Microarray analyses were performed to identify lncRNAs and mRNAs expression profiles of meniscus in young and aging adults and apple bioinformatics methods to analyse their potential roles. The differentially expressed (DE) lncRNAs and mRNAs were confirmed by qRT-PCR. A total of 1608 DE lncRNAs and 1809 DE mRNAs were identified. Functional and pathway enrichment analyses of all DE mRNAs showed that DE mRNAs were mainly involved in the TGF-beta, Wnt, Hippo, PI3K-Akt signaling pathway. The expressions of TNFRSF11B and BMP2 were significantly upregulated in aging group. LASSO logistic regression analysis of the DE lncRNAs revealed four lncRNAs (AC124312.5, HCG11, POC1B-AS1, and AP001011.1) that were associated with meniscus degradation. CNC analysis demonstrated that AP001011 inhibited the expression of TNFRSF11B and AC1243125 upregulated the expression of TNFRSF11B. CeRNA analysis suggested that POC1B-AS1 regulates the expression of BMP2 by sponging miR 130a-3p, miR136-5p, miR 18a-3p, and miR 608. Furthermore, subcellular localization and m6A modification sites prediction analysis of these four lncRNAs was performed. These data lay a foundation for extensive studies on the role of lncRNAs in change of aged meniscus.

A Tumor Accelerator Based on Multicomponent Bone Scaffolds and Cancer Cell Homing.

Bone tissue attracts cancer cell homing biologically, mechanically, or chemically. It is difficult and time consuming to identify their complex cross-talk using existed methods. In this study, a multi-component bone matrix was fabricated using gelatin, hydroxyapatite (HAp), and epidermal growth factor (EGF) as raw materials to investigate how "acellular" bone matrix affects cancer cell homing in bone. Then, EGF-responsive cancer cells were cultured with the scaffold in a dynamical bioreactor. For different culture periods, the effects of HAp, gelatin, and EGF on the cell adhesion, proliferation, 3D growth, and migration of cancer were evaluated. The results indicated that a small amount of calcium ion released from the scaffolds accelerated cancer MDA-MB-231 adhesion on the surface of inner pores. Moreover, degradable gelatin key caused cancer cell growth on the scaffold surface to turn into a 3D aggregation. Despite this, the formation of cancer spheroids was slow, and required 14 days of dynamic culture. Thankfully, EGF promoted cancer cell adhesion, proliferation, and migration, and cancer spheroids were observed only after 3-day culture. We concluded that the combination of the multiple components in this scaffold allows cancer cells to meet multiple requirements of cancer dynamic progression.

Kartogenin-Conjugated Double-Network Hydrogel Combined with Stem Cell Transplantation and Tracing for Cartilage Repair.

The effectiveness of existing tissue-engineering cartilage (TEC) is known to be hampered by weak integration of biocompatibility, biodegradation, mechanical strength, and microenvironment supplies. The strategy of hydrogel-based TEC holds considerable promise in circumventing these problems. Herein, a non-toxic, biodegradable, and mechanically optimized double-network (DN) hydrogel consisting of polyethylene glycol (PEG) and kartogenin (KGN)-conjugated chitosan (CHI) is constructed using a simple soaking strategy. This PEG-CHI-KGN DN hydrogel possesses favorable architectures, suitable mechanics, remarkable cellular affinity, and sustained KGN release, which can facilitate the cartilage-specific genes expression and extracellular matrix secretion of peripheral blood-derived mesenchymal stem cells (PB-MSCs). Notably, after tracing the transplanted cells by detecting the rabbit sex-determining region Y-linked gene sequence, the allogeneic PB-MSCs are found to survive for even 3 months in the regenerated cartilage. Here, the long-term release of KGN is able to efficiently and persistently activate multiple genes and signaling pathways to promote the chondrogenesis, chondrocyte differentiation, and survival of PB-MSCs. Thus, the regenerated tissues exhibit well-matched histomorphology and biomechanical performance such as native cartilage. Consequently, it is believed this innovative work can expand the choice for developing the next generation of orthopedic implants in the loadbearing region of a living body.