Repeated intra-articular injections of umbilical cord-derived mesenchymal stem cells for knee osteoarthritis: a phase I, single-arm study.

INTRODUCTION: Stem cell therapy has emerged as an effective treatment for multiple diseases, and some studies also demonstrate that it may be a promising treatment for osteoarthritis (OA). However, few studies have clarified the safety of repeated intra-articular injection of human umbilical cord-derived mesenchymal stem cells (UC-MSCs). To promote its application in treating OA, we conducted an open-label trial to investigate the safety of repeated intra-articular injections of UC-MSCs. METHODS: Fourteen patients with OA (Kellgrene-Lawrence grade 2 or 3) who received repeated intra-articular injections of UC-MSCs were evaluated in three months of follow-up. The primary outcomes were the adverse events, and the second outcomes included visual analog scale (VAS), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) scores and SF-12 quality of life score. RESULTS: A total of 5 of 14 patients (35.7%) experienced transient adverse reactions, which resolved spontaneously. All patients showed some improvement in knee function limitation and pain after receiving stem cell therapy. VAS score 6.0 to 3.5, WOMAC score 26.0 to 8.5, MOCART score 42.0 to 58.0, SF-12 score 39.0 to 46.0. CONCLUSION: Repeated intra-articular injection of UC-MSCs demonstrates safety in treating OA and does not induce serious adverse events. This treatment may transiently improve symptoms in patients with knee OA and may be a potential therapeutic option for OA.

A fast, simple, and cost-effective method of expanding patient-derived xenograft mouse models of pancreatic ductal adenocarcinoma.

BACKGROUND: Patient-derived xenograft (PDX) mouse models of cancer have been recognized as better mouse models that recapitulate the characteristics of original malignancies including preserved tumor heterogeneity, lineage hierarchy, and tumor microenvironment. However, common challenges of PDX models are the significant time required for tumor expansion, reduced tumor take rates, and higher costs. Here, we describe a fast, simple, and cost-effective method of expanding PDX of pancreatic ductal adenocarcinoma (PDAC) in mice. METHODS: We used two established frozen PDAC PDX tissues (derived from two different patients) and implanted them subcutaneously into SCID mice. After tissues reached 10-20 mm in diameter, we performed survival surgery on each mouse to harvest 90-95% of subcutaneous PDX (incomplete resection), allowing the remaining 5-10% of PDX to continue growing in the same mouse. RESULTS: We expanded three consecutive passages (P1, P2, and P3) of PDX in the same mouse. Comparing the times required for in vivo expansion, P2 and P3 (expanded through incomplete resection) grew 26-60% faster than P1. Moreover, such expanded PDX tissues were successfully implanted orthotopically into mouse pancreases. Within 20 weeks using only 14 mice, we generated sufficient PDX tissue for future implantation of 200 mice. Our histology study confirmed that the morphologies of cancer cells and stromal structures were similar across all three passages of subcutaneous PDX and the orthotopic PDX and were reflective of the original patient tumors. CONCLUSIONS: Taking advantage of incomplete resection of tumors associated with high local recurrence, we established a fast method of PDAC PDX expansion in mice.

Effects of vimentin disruption on the mechanoresponses of articular chondrocyte.

Human articular cartilage is subjected to repetitive mechanical loading during life time. As the only cellular component of articular cartilage, chondrocytes play a key role in the mechanotransduction within this tissue. The mechanoresponses of chondrocytes are largely determined by the cytoskeleton. Vimentin intermediate filaments, one of the major cytoskeletal components, have been shown to regulate chondrocyte phenotype. However, the contribution of vimentin in chondrocyte mechanoresponses remains less studied. In this study, we seeded goat articular chondrocytes on a soft polyacrylamide gel, and disrupted the vimentin cytoskeleton using acrylamide. Then we applied a transient stretch or compression to the cells, and measured the changes of cellular stiffness and traction forces using Optical Magnetic Twisting Cytometry and Traction Force Microscopy, respectively. In addition, to study the effects of vimentin disruption on the intracellular force generation, we treated the cells with a variety of reagents that are known to increase or decrease cytoskeletal tension. We found that, after a compression, the contractile moment and cellular stiffness were not affected in untreated chondrocytes, but were decreased in vimentin-disrupted chondrocytes; after a stretch, vimentin-disrupted chondrocytes showed a lower level of fluidization-resolidification response compared to untreated cells. Moreover, vimentin-disrupted chondrocytes didn't show much difference to control cells in responding to reagents that target actin and ROCK pathway, but showed a weaker response to histamine and isoproterenol. These findings confirmed chondrocyte vimentin as a major contributor in withstanding compressive loading, and its minor role in regulating cytoskeletal tension.

Engineering zonal cartilage through bioprinting collagen type II hydrogel constructs with biomimetic chondrocyte density gradient.

BACKGROUND: Cartilage tissue engineering is a promising approach for repairing and regenerating cartilage tissue. To date, attempts have been made to construct zonal cartilage that mimics the cartilaginous matrix in different zones. However, little attention has been paid to the chondrocyte density gradient within the articular cartilage. We hypothesized that the chondrocyte density gradient plays an important role in forming the zonal distribution of extracellular matrix (ECM). METHODS: In this study, collagen type II hydrogel/chondrocyte constructs were fabricated using a bioprinter. Three groups were created according to the total cell seeding density in collagen type II pre-gel: Group A, 2 × 10(7) cells/mL; Group B, 1 × 10(7) cells/mL; and Group C, 0.5 × 10(7) cells/mL. Each group included two types of construct: one with a biomimetic chondrocyte density gradient and the other with a single cell density. The constructs were cultured in vitro and harvested at 0, 1, 2, and 3 weeks for cell viability testing, reverse-transcription quantitative PCR (RT-qPCR), biochemical assays, and histological analysis. RESULTS: We found that total ECM production was positively correlated with the total cell density in the early culture stage, that the cell density gradient distribution resulted in a gradient distribution of ECM, and that the chondrocytes' biosynthetic ability was affected by both the total cell density and the cell distribution pattern. CONCLUSIONS: Our results suggested that zonal engineered cartilage could be fabricated by bioprinting collagen type II hydrogel constructs with a biomimetic cell density gradient. Both the total cell density and the cell distribution pattern should be optimized to achieve synergistic biological effects.

Construction of finite element model and stress analysis of anterior cruciate ligament tibial insertion.

OBJECTIVE: The aim of the present study was to develop a more realistic finite element (FE) model of the human anterior cruciate ligament (ACL) tibial insertion and to analyze the stress distribution in the ACL internal fibers under load. METHODS: The ACL tibial insertions were processed histologically. With Photoshop software, digital images taken from the histological slides were collaged, contour lines were drawn, and different gray values were filled based on the structure. The data were exported to Amira software and saved as ".hmascii" file. This document was imported into HyperMesh software. The solid mesh model generated using HyperMesh software was imported into Abaqus software. The material properties were introduced, boundary conditions were set, and load was added to carry out the FE analysis. RESULTS: The stress distribution of the ACL internal fibers was uneven. The lowest stress could be observed in the ACL lateral fibers under tensile and shear load. CONCLUSION: The establishment of ACL tibial insertion FE model and mechanical analysis could reveal the stress distribution in the ACL internal fibers under load. There was greater load carrying capacity in the ACL lateral fibers which could sustain greater tensile and shear forces.

Application of biomaterials in treating early osteonecrosis of the femoral head: Research progress and future perspectives.

Osteonecrosis of the femoral head (ONFH), a progressive pathological process of femoral head ischemia and osteocyte necrosis, is a refractory orthopedic disease caused by multiple etiologies and there is no complete cure at present. With the extension of ONFH duration, osteocyte apoptosis and trabecular bone loss can decrease the load-bearing capacity of the femoral head, which leads to the collapse of the articular cartilage and subchondral bone. Therefore, an urgent clinical need exists to develop effective treatment strategies of early-stage ONFH for maintaining the hip joint function and preventing femoral head collapse. In recent years, extensive attention has been paid to the application of diverse biomaterials in treating early ONFH for sustaining the normal morphology and function of the autologous femoral head, and slowing disease progression. Herein, we review the research progress of bone grafts, metallic materials, bioceramics, bioglasses and polymer materials for early ONFH treatment, and discuss the biological mechanisms of bone repair and regeneration in the femoral-head necrotic area. We propose suggestions for future research directions, from a special perspective of improving the local microenvironment in femoral head by facilitating vessel-associated osteoclasts (VAOs) generation and coupling of bone-specific angiogenesis and osteogenesis, as well as inhibiting bone-associated osteoclasts (BAOs) and BAO-mediated bone resorption. This review can provide ideas for the research, development, and clinical application of biomaterials for treating early ONFH. STATEMENT OF SIGNIFICANCE: We believe that at least three aspects of this manuscript make it interesting to readers of the Acta Biomaterialia. First, we briefly summarize the incidence, pathogenesis, risk factors, classification criteria and treatment of early osteonecrosis of the femoral head (ONFH). Second, we review the research progress in biomaterials for early ONFH treatment and the biological mechanisms of bone repair and regeneration in femoral-head necrotic area. Third, we propose future research progress on improving the local microenvironment in femoral head by facilitating vessel-associated osteoclasts generation and coupling of bone-specific angiogenesis and osteogenesis, as well as inhibiting bone-associated osteoclasts and bone resorption. We hope this review can provide ideas for the research, development, and clinical application of biomaterials for treating early ONFH.

Design and biomechanical analysis of patientspecific porous tantalum prostheses for knee joint revision surgery.

Artificial joint revision surgery, as an increasingly common surgery in orthopedics, often requires patient-specific prostheses to repair the bone defect. Porous tantalum is a good candidate due to its excellent abrasion and corrosion resistance and good osteointegration. Combination of 3D printing technology and numerical simulation is a promising strategy to design and prepare patient-specific porous prostheses. However, clinical design cases have rarely been reported, especially from the viewpoint of biomechanical matching with the patient's weight and motion and specific bone tissue. This work reports a clinical case on the design and mechanical analysis of 3D-printed porous tantalum prostheses for the knee revision of an 84-year-old male patient. Particularly, standard cylinders of 3D-printed porous tantalum with different pore size and wire diameters were first fabricated and their compressive mechanical properties were measured for following numerical simulation. Subsequently, patientspecific finite element models for the knee prosthesis and the tibia were constructed from the patient's computed tomography data. The maximum von Mises stress and displacement of the prostheses and tibia and the maximum compressive strain of the tibia were numerically simulated under two loading conditions by using finite element analysis software ABAQUS. Finally, by comparing the simulated data to the biomechanical requirements for the prosthesis and the tibia, a patient-specific porous tantalum knee joint prosthesis with a pore diameter of 600 µm and a wire diameter of 900 µm was determined. The Young's modulus (5719.32 ± 100.61 MPa) and yield strength (172.71 ± 1.67 MPa) of the prosthesis can produce both sufficient mechanical support and biomechanical stimulation to the tibia. This work provides a useful guidance for designing and evaluating a patient-specific porous tantalum prosthesis.

Carpal bone replacement using personalized 3D printed tantalum prosthesis.

Objective: Scaphoid and lunate fractures have a relatively high incidence rate. Traditional carpectomy and carpal arthrodesis in the treatment of carpal osteonecrosis will lead to many complications. Three-dimensional (3D) printed tantalum has good biocompatibility and can be designed to match the patient's personalized anatomical carpal structure. This study aims to investigate carpal function and prosthesis-related conditions after carpal bone replacement using 3D printed tantalum prostheses. Methods: From July 2020 to January 2022 at our center, seven patients with osteonecrosis of the carpus received carpal bone replacement using 3D printed tantalum prosthesis. The Disability of the Arm, Shoulder and Hand (DASH) score and patient satisfaction, as well as the Mayo Wrist Scores (Cooney method, modified Green, and O'Brien wrist score), were used to evaluate the preoperative and postoperative wrist function of patients. The Visual Analog Scale (VAS) pain scores were also recorded before and after surgery. The angles of flexion, dorsiflexion, ulnar deviation, and radial deviation were measured using an arthrometer. The grip strength and pinch strength of the operated hand after carpal bone replacement and the contralateral healthy carpus were measured using a dynamometer. Radiographs were taken to confirm the condition and complications of the tantalum prosthesis. Results: All seven patients were followed for 19.6 ± 2.7 months. At the last follow-up, the grip strength of the operated wrist joint after carpal bone replacement was 33.4 ± 2.3 kg, the pinch strength was 8.9 ± 0.7 kg, the flexion was 54.6° ± 0.8°, the dorsiflexion was 54.7° ± 1.7°, the ulnar deviation was 34.6° ± 1.9°, and the radial deviation was 25.9° ± 0.8°, all of which showed no statistically significant difference with the contralateral healthy carpus (p > 0.05). There were significant differences in the VAS, DASH, and MAYO scores between the preoperative and the last follow-up (p < 0.01). Patients had reduced postoperative pain and improved wrist function and range of motion (ROM), and the tantalum prostheses were stable. Conclusion: The 3D printed tantalum brings us new hope, not only for hip or knee replacement, but also for joint replacement of other complex anatomical structures, and patients with other irregular bone defects such as bone tumors and deformity, which could realize personalized treatment and precise medicine.

Turning anecdotal irradiation-induced anti-cancer immune responses into reproducible in situ cancer vaccines via disulfiram/copper-mediated enhanced immunogenic cell death of breast cancer cells.

Irradiation (IR) induces immunogenic cell death (ICD) in tumors, but it rarely leads to the abscopal effect (AE). However, combining IR with immune checkpoint inhibitors has shown anecdotal success in inducing AEs. In this study, we aimed to enhance the IR-induced immune response and generate reproducible AEs using the anti-alcoholism drug disulfiram (DSF) and copper complex (DSF/Cu) via induction of tumor ICD. We measured ICD in vitro and in vivo. In mouse tumor models, DSF/Cu was injected intratumorally followed by localized tumor IR, creating an in situ cancer vaccine. We determined the anti-cancer response by primary tumor rejection and assessed systemic immune responses by tumor rechallenge and the occurrence of AEs, i.e., spontaneous lung metastasis. Additionally, we analyzed immune cell subsets and quantified proinflammatory and immunosuppressive chemokines/cytokines in the tumor microenvironment (TME) and blood of the vaccinated mice. Immune cell depletion was investigated for its effects on the vaccine-induced anti-cancer response. The results showed that DSF/Cu and IR induced more potent ICD under hypoxia than normoxia in vitro. Low-dose intratumoral injection of DSF/Cu and IR demonstrated strong anti-primary and -rechallenged tumor effects and robust AEs in mouse models. These vaccinations also increased CD8 + and CD4 + cell numbers while decreasing Tregs and myeloid-derived suppressor cells in the 4T1 model, and increased CD8+, DC, and decreased Treg cell numbers in the MCa-M3C model. Depleting both CD8 + and CD4 + cells abolished the vaccine's anticancer response. Moreover, vaccinated tumor-bearing mice exhibited increased TNFα levels and reduced levels of immunosuppressive chemokines/cytokines. In conclusion, our novel approach generated an anti-cancer immune response, resulting in a lack of or low tumor incidence post-rechallenge and robust AEs, i.e., the absence of or decreased spontaneous lung metastasis in tumor-bearing mice. This approach is readily translatable to clinical settings and may increase IR-induced AEs in cancer patients.

Analysis of the mineral composition of the human calcified cartilage zone.

As the connecting tissue between the hyaline articular cartilage and the subchondral bone, calcified cartilage zone (CCZ) plays a great role in the force transmission and materials diffusion. However, the questions that remain to be resolved are its mineral composition and organization. In this study, 40 healthy human knee specimens were harvested; first the CCZ was dissected and observed by Safranin O/fast green staining, then CCZ chemical characteristics were measured by using amino acid assay and X-ray diffraction. The percentage of dry weight of type II collagen as an organic compound of CCZ was 20.16% ± 0.96%, lower than that of the hyaline cartilage layer (61.39% ± 0.38%); the percentage of dry weight of hydroxyapatite as an inorganic compound was 65.09% ± 2.31%, less than that of subchondral bone (85.78% ± 3.42%). Our study provides the accurate data for the reconstruction of the CCZ in vitro and the elucidation of CCZ structure and function.

Anterior cruciate ligament reconstruction with bone-patellar tendon-bone graft: comparison of autograft, fresh-frozen allograft, and γ-irradiated allograft.

PURPOSE: To compare clinical follow-up results of anterior cruciate ligament (ACL) reconstruction using (1) autologous, (2) fresh-frozen allogeneic, and (3) γ-irradiated allogeneic bone-patellar tendon-bone (BPTB). METHODS: From February 2002 to January 2006, 187 patients received BPTB ACL reconstruction at our center. One hundred forty-two consecutive patients who had received single-bundle BPTB ACL reconstruction were included in this study. Of these patients, 41 had autografts, 33 had fresh-frozen allografts, and 68 had γ-irradiated allografts. Clinical results were evaluated with the KT-1000 maximum displacement test (MEDmetric, San Diego, CA), Lachman test, and Lysholm, Irrgang, and Larson activity scales. RESULTS: The mean duration of follow-up was 6.7 ± 1.5 years (range, 4.2 to 8.2 years). There were 3 cases of acute synovitis due to immunologic rejection (fresh-frozen allografts) and 6 cases of failure (γ-irradiated allografts). KT-1000 examination showed more anterior laxity in the γ-irradiated allograft group compared with the autograft and fresh-frozen allograft groups (P < .05). The Lysholm, Irrgang, and Larson activity scales showed no difference among the 3 groups (P > .05). CONCLUSIONS: The study showed a statistically poorer KT-1000 result and higher failure rate in the γ-irradiated allograft group compared with the autograft and fresh-frozen allograft groups. This may suggest that γ-irradiated allograft is not a good candidate graft for ACL reconstruction. Power analysis showed that the study was underpowered, so further research and longer follow-up study are needed to make this point clearer. LEVEL OF EVIDENCE: Level III, retrospective comparative study.

Long-term survival analysis of posterior cruciate-retaining total knee arthroplasty.

PURPOSE: Clinical factors related to cruciate-retaining knee arthroplasty failure in a long-term follow-up are yet unclear. The study was designed to evaluate the long-term survival rate of cruciate-retaining arthroplasty and clinical factors that may contribute to its failure. METHODS: A total of 162 patients (188 knees) who received cruciate-retaining press-fit condylar arthroplasty from June 1993 to May 1994 were followed up. All patients were assessed clinically and radiographically. Revision for any reason was regarded as failure of arthroplasty. RESULTS: A total of 120 patients (138 knees) were successfully followed up. Survivorship over 17 years was 92.5%. Fourteen knees were revised. Tibial varus angle of the operated knee in the unrevised patient group was greater than in revised group. There was statistical difference between these two groups (P < 0.05). CONCLUSION: Long-term survivorship of cruciate-retaining arthroplasty was fair. Varus and valgus deformity of the unoperated contralateral knee and tibial varus deformity of the operated knee could be important factors related to arthroplasty failure. CLINICAL RELEVANCE: This long-term follow-up result of Press-Fit Condylar cruciate-retaining arthroplasty was good considering it was an old design. The alignment of the operated knee and deformity of the unoperated contralateral knee are important clinical factors that should be paid attention to avoid unexpected arthroplasty failure. LEVEL OF EVIDENCE: IV.

Bone marrow-derived mesenchymal stem cells versus bone marrow nucleated cells in the treatment of chondral defects.

PURPOSE: The aim of this study was to compare bone marrow-derived mesenchymal stem cells (MSCs) with bone marrow nucleated cells (BNCs) as seed cells in the treatment of cartilage defects. METHODS: Twenty Guizhou minipigs were used to create full-thickness chondral defects of 6.0 mm in diameter in the knee joints and divided between two time points (four and eight weeks) for final assessment. At every time point, animals were separated into four groups: the CON group which underwent no implantation; the collagen type II hydrogel group (COL); the collagen type II hydrogel + bone marrow-derived MSCs group; and the collagen type II hydrogel + BNCs group. The samples were grossly examined, observed through a stereo microscope, histologically analysed and evaluated with the O'Driscoll scoring system, respectively. RESULTS: The cartilage repair of the two cell-treated groups was improved markedly compared to the CON and the COL groups, while the repair tissues of the two cell-treated groups showed no significant difference eight weeks after surgery. CONCLUSIONS: These data indicate that BNCs contribute to the repair of cartilage with collagen type II hydrogel as scaffolds, which have comparable results with bone marrow-derived MSCs. Moreover, the transplantation of autologous BNCs as seed cells may be a more economical and convenient technique for cartilage repair in clinical applications.

[Effects of superparamagnetic iron-oxide particles-labeling on the multi-diffentiation of rabbit marrow mesenchymal stem cell in vitro].

The aim of this study was to label rabbit bone derived mesenchymal stem cells (BMSCs) with superparamagnetic iron oxide particles (SPIO) and to study the effects of magnetic labeling on the multi-differentiation of BMSCs. Rabbit BMSCs were isolated, purified, expanded, then coincubated with SPIO(25 microg/ml) complexed to protamine sulfate (Pro) transfection agents overnight. Prussian blue staining and transmission electron microscopy were performed to show intracellular iron. Cell differentiation was evaluated. Both labeled and unlabeled BMSCs were subjected to osteogenic, adipogenic and chondrogenic differentiation to assess their differentiation capacity for 21 d. Osteogenic cells were stained with alizarin red to reveal calcium deposition, adipogenic cells were stained with oil redO' respectively. Chondrogenic cells stained with Safranin-O, glycosamino glycans, and type II collagen production was assessed by standard immunohistochemistry. Cell with immunohistochemistry staining were detected by polarized light microscopy and analysed by Image-Pro Plus software. The results showed that intracytoplasmic nanoparticles were stained with Prussian blue and observed by transmission electron microscopy clearly except the unlabeled control. As compared with the nonlabeled cells, it showed no statistically significant difference on the differentiation of the labeled BMSCs. And the differentiation of the labeled cells were unaffected by the endosomal incorporation of SPIO. In summary, BMSCs can be labeled with SPIO without significant change in cell multi-differentiation capacity.

Advanced Hydrogels With Nanoparticle Inclusion for Cartilage Tissue Engineering.

Cartilage dysfunctions caused by congenital disease, trauma and osteoarthritis are still a serious threat to joint activity and quality of life, potentially leading to disability. The relatively well-established tissue engineering technology based on hydrogel is a promising strategy for cartilage defect repairing. However, several unmet challenges remain to be resolved before its wide application and clinical translation, such as weak mechanical property and compromised bioactivity. The development of nanomedicine has brought a new dawn to cartilage tissue engineering, and composite hydrogel containing nanoparticles can substantially mimic natural cartilage components with good histocompatibility, demonstrating unique biological effects. In this review, we summarize the different advanced nanoparticle hydrogels currently adopted in cartilage tissue engineering. In addition, we also discuss the various application scenarios including injection and fabrication strategies of nanocomposite hydrogel in the field of cartilage repair. Finally, the future application prospects and challenges of nanocomposite hydrogel are also highlighted.

Hydrogel composed of type II collagen, chondroitin sulfate and hyaluronic acid for cartilage tissue engineering.

BACKGROUND: Cartilage tissue engineering is a promising way to repair cartilage defects. Different materials have been applied in the preparation of cartilage hydrogels, but all with various disadvantages. OBJECTIVE: The aim of this study was to prepare cartilage hydrogel using type II collagen, chondroitin sulfate and hyaluronic acid, to explore their gelation effect and compressive strength, and to analyze the feasibility of their application in cartilage tissue engineering. METHODS: Type II collagen (Col II), hyaluronic acid (HA) and chondroitin sulfate (CS) were mixed in a certain proportion to prepare gel scaffolds; changes in chemical groups were detected by Fourier transform infrared. After the hydrogel was prepared, its compressive strength was measured. Umbilical cord stem cells were co-cultured with hydrogel scaffolds to observe its cytocompatibility and analyze whether stem cells had cellular activity during co-culture; histological staining was applied to observe the hydrogel loaded with stem cells. RESULTS: Cartilage hydrogels were successfully prepared with good compressive strength, and Fourier transform infrared analysis showed that Schiff base reaction occurred during the preparation process and tight chemical cross-linking was formed. The results of umbilical cord stem cell co-culture showed that the hydrogel had good cytocompatibility and the stem cells had good activity in the hydrogel. CONCLUSIONS: Cartilage hydrogels with stable structures were successfully prepared and had good compressive strength. Hydrogel scaffold could provide a suitable living environment for umbilical cord stem cells, so that they maintain normal cell morphology and activity, and has a good application potential in cartilage tissue engineering.

Application of three-dimensional-printed porous tantalum cones in total knee arthroplasty revision to reconstruct bone defects.

Purpose: Three-dimensional (3D) printing technology has emerged as a new treatment method due to its precision and personalization. This study aims to explore the application of a 3D-printed personalized porous tantalum cone for reconstructing the bone defect in total knee arthroplasty (TKA) revision. Methods: Between November 2017 and October 2020, six patients underwent bone reconstruction using 3D-printed porous tantalum cones in TKA revision. The knee function was assessed using the Hospital for Special Surgery (HSS) score pre- and postoperatively. The pain was measured by the visual analog scale (VAS) pre- and postoperatively. The quality of life was measured using the 36-Item Short Form Health Survey (SF-36) to pre- and postoperatively evaluate the relief of pain. Operation time, intraoperative blood loss, postoperative drainage volume, and complications were also recorded. At the last follow-up, all patients received X-ray and computed tomography (CT) to confirm the effect of bone reconstruction. Results: After an average follow-up duration of 26.3 months, no patients developed any operation-related complications. The average intraoperative blood loss and postoperative drainage volumes were 250.1 ± 76.4 ml and 506.7 ± 300.8 ml, respectively. At the last follow-up, the HSS score was significantly higher than that before operation, indicating that the knee function was significantly improved (p < 0.001). During the follow-up, the mean VAS score decreased and the mean SF-36 score increased, both of which were significantly improved compared with preoperative conditions (p < 0.001). Radiological examination at the final follow-up showed that cones implanted into the joint were stable and bone defects were effectively reconstructed. Conclusion: This study demonstrated that 3D-printed porous tantalum cones could effectively reconstruct bone defects and offer anatomical support in TKA revision. Further studies are still needed to confirm the long-term effect of 3D-printed tantalum cones for reconstructing bone defects.

Scaffold With Natural Calcified Cartilage Zone for Osteochondral Defect Repair in Minipigs.

BACKGROUND: Long-term outcomes of current clinical interventions for osteochondral defect are less than satisfactory. One possible reason is an ignorance of the interface structure between cartilage and subchondral bone, the calcified cartilage zone (CCZ). However, the importance of natural CCZ in osteochondral defects has not been directly described. PURPOSE: To explore the feasibility of fabricating trilayer scaffold containing natural CCZ for osteochondral defects and the role of CCZ in the repair process. STUDY DESIGN: Controlled laboratory study. METHODS: The scaffold was prepared by cross-linking lyophilized type II collagen sponge and acellular normal pig subchondral bone with or without natural CCZ. Autologous bone marrow stem cells (BMSCs) of minipig were mixed with type II collagen gel and injected into the cartilage layer of the scaffold before operation. Thirty minipigs were randomly divided into CCZ (n = 10), non-CCZ (n = 10), and blank control (n = 10) groups. An 8 mm-diameter full-thickness osteochondral defect was created on the trochlear surface, and scaffold containing BMSCs was transplanted into the defect according to grouping requirements. At 12 and 24 weeks postoperatively, specimens were assessed by macroscopic observation, magnetic resonance imaging examination, and histological observations (hematoxylin and eosin, Safranin O-fast green, type II collagen immunohistochemical, and Sirius red staining). Semiquantitative cartilage repair scoring was conducted using the MOCART (Magnetic Resonance Observation of Cartilage Repair Tissue) system and the O'Driscoll repaired cartilage value system. RESULTS: The defects in the blank control and non-CCZ groups were filled with fibrous tissue, while the cartilage layer of the CCZ group was mainly repaired by hyaline cartilage at 24 weeks postoperatively. The superior repair outcome of the CCZ group was confirmed by MOCART and O'Driscoll score. CONCLUSION: The trilayer scaffold containing natural CCZ obtained the best repair effect compared with the non-CCZ scaffold and the blank control, indicating the importance of the CCZ in osteochondral tissue engineering. CLINICAL RELEVANCE: This study demonstrates the necessity to reconstruct CCZ in clinical osteochondral defect repair and provides a possible strategy for osteochondral tissue engineering.

Personalized three-dimensional printed polyether-ether-ketone prosthesis for reconstruction after subtotal removal of chronic clavicle osteomyelitis: A case report.

RATIONALE: Three-dimensional (3D) printing has attracted wide attention for its potential and abilities in the assistance of surgical planning and the development of personalized prostheses. We herewith report a unique case of chronic clavicle osteomyelitis treated with a two-stage subtotal clavicle reconstruction using a 3D printed polyether-ether-ketone (PEEK) prosthesis. PATIENT CONCERNS: A 23-year-old Chinese female presented to our clinic complaining about a progressive pain of her right clavicle for about 1 year. DIAGNOSES: Chronic clavicle osteomyelitis confirmed by percutaneous biopsy and lesion biopsy. INTERVENTIONS: This patient accepted a long-term conservative treatment, which did not gain satisfactory outcomes. Thus, a subtotal removal and two-stage reconstruction of the right clavicle with a 3D-printed polyether-ether-ketone prosthesis stabilized by screw fixation system was performed. OUTCOMES: At 2-year follow-up, complete pain relief and satisfactory functional recovery of her right shoulder were observed. LESSONS: Personalized 3D printed prosthesis is an effective and feasible method for reconstruction of complex bone defects.

Applications of Multi-Omics Technologies for Crop Improvement.

Multiple "omics" approaches have emerged as successful technologies for plant systems over the last few decades. Advances in next-generation sequencing (NGS) have paved a way for a new generation of different omics, such as genomics, transcriptomics, and proteomics. However, metabolomics, ionomics, and phenomics have also been well-documented in crop science. Multi-omics approaches with high throughput techniques have played an important role in elucidating growth, senescence, yield, and the responses to biotic and abiotic stress in numerous crops. These omics approaches have been implemented in some important crops including wheat (Triticum aestivum L.), soybean (Glycine max), tomato (Solanum lycopersicum), barley (Hordeum vulgare L.), maize (Zea mays L.), millet (Setaria italica L.), cotton (Gossypium hirsutum L.), Medicago truncatula, and rice (Oryza sativa L.). The integration of functional genomics with other omics highlights the relationships between crop genomes and phenotypes under specific physiological and environmental conditions. The purpose of this review is to dissect the role and integration of multi-omics technologies for crop breeding science. We highlight the applications of various omics approaches, such as genomics, transcriptomics, proteomics, metabolomics, phenomics, and ionomics, and the implementation of robust methods to improve crop genetics and breeding science. Potential challenges that confront the integration of multi-omics with regard to the functional analysis of genes and their networks as well as the development of potential traits for crop improvement are discussed. The panomics platform allows for the integration of complex omics to construct models that can be used to predict complex traits. Systems biology integration with multi-omics datasets can enhance our understanding of molecular regulator networks for crop improvement. In this context, we suggest the integration of entire omics by employing the "phenotype to genotype" and "genotype to phenotype" concept. Hence, top-down (phenotype to genotype) and bottom-up (genotype to phenotype) model through integration of multi-omics with systems biology may be beneficial for crop breeding improvement under conditions of environmental stresses.