Background All-suture anchor (ASA) is a special type of suture anchor. It has been used to repair rotator cuff tears (RCTs). However, mechanical properties and tendon-bone integration at different time postoperatively remains to be unclear. Methods Mechanical testing and water contact angle measurements were conducted for ASA. In vitro biocompatibility was assessed using rat bone marrow stem cells (BMSCs), including live/dead cell staining and Cell Counting Kit-8 assays. ASA was implanted for rotator cuff repair (ASA group) in a New Zealand White rabbit model of RCTs, and a natural rotator cuff was used as a control (natural group). The animals were sacrificed, and tissue samples were harvested for biomechanical, radiographic, and histological analysis at 4, 8, and 12 weeks postoperatively. Results ASA was hydrophobic and had a strong mechanical property in vitro. The biocompatibility analysis showed that ASA had no effect on the viability of BMSCs. Mechanical testing in vivo revealed that a gradually improved failure load of ASA group was 118.0 ± 22.53N at 12 weeks postoperatively, which was recovered to the natural group. Micro-CT analysis indicated that an initial decrease in BMD and trabecular quality following ASA implantation, with a slight recovery observed at 12 weeks. Additionally, histological analysis showed the tendon-bone interface gradually integrated in the ASA group. A significant increase in tendon-bone interface scores was found from 4 weeks to 12 weeks. Tendon maturing score also improved in the ASA group, and Type I collagen content recovered to 18.58 ± 4.378% at 12 weeks and no different from that of the natural group. Conclusion Rotator cuff repair with ASA in a rabbit model demonstrated the capacity to enhance biomechanical properties and tendon-bone integration.

Artificial graft serves as the primary grafts used in the clinical management of sports-related injuries. Until now, optimizing its graft-host integration remains a great challenge due to the excessive inflammatory response during the inflammatory phase, coupled with an absence of tissue-inductive capacity during the regeneration phase. Here, a multi-layered regenerated silk fibroin (RSF) coating loaded with curcumin (Cur) and Zn2+ on the surface of the PET grafts (Cur@Zn2+@PET) was designed and fabricated for providing time-matched regulation specifically tailored to address issues arising at both inflammatory and regeneration phases, respectively. The release of Cur and Zn2+ from the Cur@Zn2+@PET followed a time-programmed pattern in vitro. Specifically, cellular assays revealed that Cur@Zn2+@PET initially released Cur during the inflammatory phase, thereby markedly inhibit the expression of inflammatory cytokines TNF-a and IL-1β. Meanwhile, a significant release of Zn2+ was major part during the regeneration phase, serving to induce the osteogenic differentiation of rBMSC. Furthermore, rat model of anterior cruciate ligament reconstruction (ACLR) showed that through time-programmed drug release, Cur@Zn2+@PET could suppress the formation of fibrous interface (FI) caused by inflammatory response, combined with significant new bone (NB) formation during regeneration phase. Consequently, the implementation of the Cur@Zn2+@PET characterized by its time-programmed release patterns hold considerable promise for improving graft-host integration for sports-related injuries.

Continuous monitoring of biomechanical signals generated from the injured Achilles tendon is essential for the deep understanding of the recovery or rehabilitation process, thus decreasing the risk of secondary injuries. With tissue-like components and adjustable properties, hydrogel-based biomechanical sensors are considered promising materials for human motion detection. However, existing hydrogels are characterized by inferior mechanical properties with strength and modulus typically lower than 1 MPa, as well as poor stability under physiological conditions, which hampers their applications in implantable devices. Moreover, acquiring the stress signal from collected electrical signals remains challenging. Herein, based on the regulation of polymer aggregation, a high-strength fibrous sensor composed of polyvinyl alcohol (PVA) and reduced graphene oxide (rGO) for in vivo monitoring is prepared through a two-step procedure, including freeze-thaw and freeze-soak. Benefiting from the synergy of crystallization, Hofmeister effect and nanocomposite, the hydrogel fibers feature high tensile strength (8.34 ± 0.66 MPa) and elastic modulus (1.15 ± 0.10 MPa). Meanwhile, the removal of salt ions during fabrication improves the water content (69.18 ± 1.47%) and anti-swelling performance of such fibers and minimizes side effects after implantation. It is demonstrated that the fibrous sensor could record the relative resistance changes upon stretching with ideal sensitivity (GF = 1.57) and convert them into bearing stress through formula derivation and calculations. In vitro and in vivo assays further confirm its feasibility for real-time monitoring of joint motion, providing important references for medical diagnosis and treatment.

Background: Extracorporeal shock wave therapy (ESWT) promotes tissue healing by modulating inflammation, which has implications for meniscal tear healing in the avascular zone. Purpose: To evaluate the effects of a single dose of radial ESWT on the healing process and inflammation of the meniscus and knee joints after meniscal tears in the avascular zone. Study Design: Controlled laboratory study. Methods: Avascular tears were induced in the medial meniscus (MM) of 72 Sprague-Dawley rats. One week postoperatively, the rats received a single session of radial ESWT with a Power+ handpiece (ESWT group; n = 36) or with a fake handpiece (sham-ESWT group; n = 36). The rats were then euthanized at 2, 4, or 8 weeks postoperatively. The MMs were harvested for analysis of healing (hematoxylin-eosin, safranin O–Fast Green, and collagen type 2 staining) and inflammation (interleukin [IL]-1β and IL-6 staining). Lateral menisci and synovia were obtained to evaluate knee joint inflammation (enzyme-linked immunosorbent assay of IL-1β and IL-6). Cartilage degeneration was assessed in the femurs and tibial plateaus using safranin O–Fast Green staining. Results: The ESWT group showed significantly better meniscal healing scores than the sham-ESWT group at 4 ( P = .0066) and 8 ( P = .0050) weeks postoperatively. The IL-1β level was significantly higher in the sham-ESWT group than in the ESWT group at 2 (MM: P = .0009; knee joint: P = .0160) and 8 (MM: P = .0399; knee joint: P = .0001) weeks. The IL-6 level was significantly lower in the sham-ESWT group than in the ESWT group at 2 (knee joint: P = .0184) and 4 (knee joint: P = .0247) weeks but higher at 8 weeks (MM: P = .0169; knee joint: P = .0038). The sham group had significantly higher osteoarthritis scores than the ESWT group at 4 (tibial plateau: P = .0157) and 8 (femur: P = .0048; tibial plateau: P = .0359) weeks. Conclusion: A single dose of radial ESWT promoted meniscal tear healing in the avascular zone, modulated inflammatory factors in the menisci and knee joints in rats, and alleviated cartilage degeneration. Clinical Relevance: Radial ESWT can be considered a potential option for improving meniscal tear healing in the avascular zone because of its ability to modulate inflammation.

Artificial graft serves as the primary grafts used in the clinical management of sports-related injuries. Until now, optimizing its graft-host integration remains a great challenge due to the excessive inflammatory response during the inflammatory phase, coupled with an absence of tissue-inductive capacity during the regeneration phase. Here, a multi-layered regenerated silk fibroin (RSF) coating loaded with curcumin (Cur) and Zn2+ 2 + on the surface of the PET grafts (Cur@Zn2+@PET) 2 + @PET) was designed and fabricated for providing time-matched regulation specifically tailored to address issues arising at both inflammatory and regeneration phases, respectively. The release of Cur and Zn2+ 2 + from the Cur@Zn2+@PET 2 + @PET followed a time-programmed pattern in vitro. Specifically, cellular assays revealed that Cur@Zn2+@PET 2 + @PET initially released Cur during the inflammatory phase, thereby markedly inhibit the expression of inflammatory cytokines TNF-a and IL-1(3. Meanwhile, a significant release of Zn2+ 2 + was major part during the regeneration phase, serving to induce the osteogenic differentiation of rBMSC. Furthermore, rat model of anterior cruciate ligament reconstruction (ACLR) showed that through time-programmed drug release, Cur@Zn2+@PET 2 + @PET could suppress the formation of fibrous interface (FI) caused by inflammatory response, combined with significant new bone (NB) formation during regeneration phase. Consequently, the implementation of the Cur@Zn2+@PET 2 + @PET characterized by its time-programmed release patterns hold considerable promise for improving graft-host integration for sports-related injuries.

Skeletal muscle has a robust regeneration ability that is impaired by severe injury, disease, and aging, resulting in a decline in skeletal muscle function. Therefore, improving skeletal muscle regeneration is a key challenge in treating skeletal muscle-related disorders. Owing to their significant role in tissue regeneration, implantation of M2 macrophages (M2Mø) has great potential for improving skeletal muscle regeneration. Here, we present a short-wave infrared (SWIR) fluorescence imaging technique to obtain more in vivo information for an in-depth evaluation of the skeletal muscle regeneration effect after M2Mø transplantation. SWIR fluorescence imaging was employed to track implanted M2Mø in the injured skeletal muscle of mouse models. It is found that the implanted M2Mø accumulated at the injury site for two weeks. Then, SWIR fluorescence imaging of blood vessels showed that M2Mø implantation could improve the relative perfusion ratio on day 5 (1.09 ± 0.09 vs 0.85 ± 0.05; p = 0.01) and day 9 (1.38 ± 0.16 vs 0.95 ± 0.03; p = 0.01) post-injury, as well as augment the degree of skeletal muscle regeneration on day 13 post-injury. Finally, multiple linear regression analyses determined that post-injury time and relative perfusion ratio could be used as predictive indicators to evaluate skeletal muscle regeneration. These results provide more in vivo details about M2Mø in skeletal muscle regeneration and confirm that M2Mø could promote angiogenesis and improve the degree of skeletal muscle repair, which will guide the research and development of M2Mø implantation to improve skeletal muscle regeneration.

BACKGROUND:Although meniscal injury is common after anterior cruciate ligament (ACL) injury, the underlying process in different meniscal regions remains unclear.PURPOSE:To investigate macroscopic and histological alterations in different meniscal regions in an ACL transection (ACLT) rabbit model.STUDY DESIGN:Controlled laboratory study.METHODS:ACLT was performed on New Zealand White rabbits. Both the medial meniscus (MM) and the lateral meniscus (LM) of the ACLT knees were obtained at 8 (n = 6) and 26 (n = 6) weeks postoperatively. MM and LM collected from nonoperated knees were considered 0 weeks (n = 6) postoperatively. Menisci were then divided into posterior, central, and anterior regions for macroscopic (width) and histological (hematoxylin and eosin, safranin O/fast green, collagen type 2 [COL2]) analysis.RESULTS:The macroscopic widths of MM and LM increased and then decreased over 26 weeks postoperatively, with all 3 MM widths at 8 weeks significantly wider than at 0 weeks (posterior: P < .01; central: P < .05; anterior: P < .05). In the MM, chondrocyte-like cell density increased and then decreased postoperatively, whereas in the LM, it decreased and then remained almost unchanged. Cell density was significantly higher in the central MM region at 8 weeks than at 0 weeks (P < .05). Glycosaminoglycan (GAG) and COL2 percentages of MM and LM decreased from 0 to 8 weeks and then returned to nearly normal levels at 26 weeks postoperatively. In the MM, the GAG percentage in the posterior (P < .05) and central (P < .01) regions and the COL2 percentage in the posterior region (P < .05) was significantly lower at 8 weeks than at 0 weeks.CONCLUSION:After ACLT in rabbit meniscus, the extracellular matrix (ECM) initially decreased and then increased to almost normal. Additionally, there were significant differences in the ECM percentage in the posterior and central regions of the MM in comparison with other meniscal regions between 0 and 8 weeks postoperatively.CLINICAL RELEVANCE:The results indicate that the time for meniscal injury after ACL injury is important, and attention should be paid to the posterior and central regions of the MM after ACLT.

OBJECTIVE:Blood supply to the meniscus determines its recovery and is a reference for treatment planning. This study aimed to apply tissue clearing and three-dimensional (3D) imaging in exploring the quantitative distribution of blood vessels in the mouse meniscus.MATERIALS AND METHODS:In this experimental study, tissue clearing was performed to treat the bilateral knee joints of transgenic mice with fluorescent vascular endothelial cells. Images were acquired using a light sheet microscope and the vascular endothelial cells in the meniscus was analysed using 3D imaging. Quantitative methods were employed to further analyse the blood vessel distribution in the mouse meniscus.RESULTS:The traditional three-equal-width division of the meniscus is as follows: the outer one-third is the red-red zone (RR), the inner one-third is the white-white zone (WW), and the transition area is the red-white zone (RW). The division revealed significant signal differences between the RW and WW (P<0.05) zones, but no significant differences between the RR and RW zones, which indicated that the division might not accurately reflect the blood supply of the meniscus. According to the modified division (4:2:1) in which significant differences were ensured between the adjacent zones, we observed that the width ratio of each zone was 38 ± 1% (RR), 24 ± 1% (RW), and 38 ± 2% (WW). Furthermore, the blood supply to each region was verified. The anterior region had the most abundant blood supply. The fluorescence count in the anterior region was significantly higher than in the central and posterior regions (P<0.05). The blood supply of the medial meniscus was superior to the lateral meniscus (P<0.05).CONCLUSION:Analysis of the blood supply to the mouse meniscus under tissue clearing and 3D imaging reflect quantitative blood vessel distribution, which would facilitate future evaluations of the human meniscus and provide more anatomical references for clinicians.

Background:Anterior cruciate ligament (ACL) reinjury after ACL reconstruction (ACLR) can occur on the ipsilateral or contralateral side. Limited evidence exists regarding the difference between the incidence of reinjury to either knee, which is important in developing interventions to prevent ACL reinjury. Purpose:To compare the reinjury rate of the ACL on the ipsilateral side versus the contralateral side in athletes after ACLR and investigate the risk factors that may cause different reinjury rates between the sides. Study Design:Systematic review; Level of evidence, 4. Methods:A systematic review was performed based on the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. Studies that involved ACL reinjury in athletes after ACLR were reviewed. Considering several risk factors, including age and sex, a comparison of ACL reinjury incidence on the ipsilateral and contralateral sides was performed using a meta-analysis. Results:Of the 17 selected studies, 3 were found to be at high risk of bias, and thus, 14 (n = 3424 participants) studies were included in the meta-analysis. In this athletic population, the contralateral ACL had a significantly higher rupture rate than the ipsilateral graft (risk ratio [RR], 1.41; P < .0001). Female athletes were found to have a greater risk of ACL reinjury on the contralateral versus the ipsilateral side (RR, 1.65; P = .0005), but different results were found in male athletes. (RR, 0.81; P = .21). There was no statistical difference in the incidence rate of ACL reinjury to either side in adolescent athletes (RR, 1.15; P = .28). Conclusion:The contralateral ACL was more vulnerable to reinjury than the ipsilateral side in athletes after ACLR. Female athletes were more likely to reinjure their contralateral native ACL, while the same trend was not found in their male counterparts. The reinjury rate was comparable in both knees in adolescent athletes.

BACKGROUND:Although nondegradable synthetic grafts for bridging reconstruction of massive rotator cuff tears (MRCTs) have shown satisfactory clinical outcomes, their function and details on graft-tendon healing and enthesis regeneration have not been fully studied.HYPOTHESIS:The knitted polyethylene terephthalate (PET) patch as a nondegradable synthetic graft could provide sustained mechanical support, facilitating enthesis and tendon regeneration in the treatment of MRCTs.STUDY DESIGN:Controlled laboratory study.METHODS:A knitted PET patch was fabricated for bridging reconstruction (PET group) in a New Zealand White rabbit model of MRCTs (negative control group), and an autologous Achilles tendon was used as a control (autograft group). The animals were sacrificed, and tissue samples were harvested for gross observation as well as histological and biomechanical analyses at 4, 8, and 12 weeks postoperatively.RESULTS:Histological analysis showed no significant difference in the graft-bone interface score between the PET and autograft groups at 4, 8, and 12 weeks postoperatively. Interestingly, in the PET group, Sharpey-like fibers were observed at 8 weeks, while fibrocartilage formation and the ingrowth of chondrocytes were recognized at 12 weeks. Meanwhile, the tendon maturing score was significantly higher in the PET group than in the autograft group (19.7 ± 1.5 vs 15.3 ± 1.2, respectively; P = .008) at 12 weeks, with parallel-oriented collagen fibers around the knitted PET patch. Moreover, the ultimate failure load of the PET group was similar to that of a healthy rabbit tendon at 8 weeks (125.6 ± 13.6 vs 130.8 ± 28.6 N, respectively; P > .05) and no different from that of the autograft group at 4, 8, and 12 weeks.CONCLUSION:The knitted PET patch could not only immediately reconstruct the mechanical support for the torn tendon postoperatively in the rabbit model of MRCTs but also enhanced maturation of the regenerated tendon by fibrocartilage formation and improved the organization of collagen fibers. Herein, the knitted PET patch could be a promising candidate graft adopted in bridging reconstruction of MRCTs.CLINICAL RELEVANCE:A nondegradable knitted PET patch can safely bridge MRCTs with satisfactory mechanical strength and the promotion of tissue regeneration.

Graft-host integration after the anterior cruciate ligament (ACL) reconstruction sequentially follows the prognosis from the inflammation period to the regeneration period. However, due to insufficient bioactivity, polyethylene terephthalate (PET) artificial ligaments often require a long period for graft-host integration. To improve graft-host integration, sequential therapy targeting multifactor is widely advocated. In this study, a multilayer regenerated silk fibroin (RSF) coating loaded with heparin and bone morphogenetic protein binding peptide (BBP) for differentiated release was introduced on the surface of the PET artificial ligament by a stepwise deposition method. The drug release profiles of heparin and BBP on the coated PET artificial ligament indicated the features of differential drug release, i.e., with heparin in the outermost layer releasing a significant amount (more than 60%) during the first 5 days while BBP in the inner layer only releasing a small amount (ca. 30%) within 1 week without burst release. Based on the isometric ACL reconstruction model of rabbits, such drug-loaded RSF coating was verified to be able to modulate the early inflammatory response and promote the maturation of the graft in the articular cavity, meanwhile, it provided a continuous and stable signal of osteogenic induction to improve graft-bone integration. Thus, sequential intervention with heparin and BBP proved to be a reliable combination, and multifunctional RSF-coated PET artificial ligaments hold great potential for improving the clinical efficacy of ACL reconstruction.

Here, fluorescent carbon nanodots (CNDs) were generated using water extract of tomato leaves. Sphere nanodots were formed within 30 min by a one-step microwave heating. An ultraviolet 360 nm photoluminescence (PL) peak was found upon high-energy excitation. This peak showed excitation-independent property, and might belong to some solely-emitting fluorescent moieties attaching to the CNDs. The biomolecules with complex chemical structure in the plant leaves were responsible for the unique spectral property of the CNDs. Taking advantage of their special property, the CNDs were applied as an fluorescent probe for spectral-matching sensing of chromium(VI) [Cr(VI)] in the aqueous solution. The detection limit was as low as 79 nM, and the CNDs probe showed good selectivity towards other metal ions. Real sample tests using the tap water were also carried out, showing potential of the CNDs in the practical applications.

Double-layer metal structures show strong fields coupling when the distance between two metal layers is certain. Here, we have investigated the terahertz transmission properties of a composite slab composed of double-layer metal complementary periodic cross-shaped resonators (CPCRs). By carefully altering the spacing between two metal layers, new abnormal peaks are split from the lowest resonant modes and thus multi-band filters can be achieved, which originates from the enhanced coupling between the localized fields on the metal surfaces. Embedded a dielectric layer in the spacing of two layers, the transmission properties of the composite slabs can also be manipulated. A distinct frequency shift and transmittance changes at the resonant peak are observed as the refractive index and material absorption alters. The sensitivity using our proposed slab is up to 0.30 THz/RIU. Furthermore, the transmittance at resonant peak distinctly decreases as the loss of membranes increases. Such transmittance change reaches 67% when the membrane loss is about 0.10 cm−1. These results show that the composite slab has the potential to be applied for molecular fingerprint detection with high sensitivity as well as narrow bandwidth filters in terahertz regions.