A high throughput bispecific antibody discovery pipeline.

Bispecific antibodies (BsAbs) represent an emerging class of immunotherapy, but inefficiency in the current discovery has limited their broad clinical availability. Here we report a high throughput, agnostic, single-cell-based functional screening pipeline, comprising molecular and cell engineering for efficient generation of BsAb library cells, followed by functional interrogation at the single-cell level to identify and sort positive clones and downstream sequence identification and functionality characterization. Using a CD19xCD3 bispecific T cell engager (BiTE) as a model, we demonstrate that our single-cell platform possesses a high throughput screening efficiency of up to one and a half million variant library cells per run and can isolate rare functional clones at a low abundance of 0.

Clinical Efficacy of Intra-Articular Injection with P-PRP Versus that of L-PRP in Treating Knee Cartilage Lesion: A Randomized Controlled Trial.

Objective: Platelet-rich plasma（PRP), with different concentration of leukocytes, may lead to varying effects in the treatment of cartilage lesions. So far, current research has not shown enough evidence on this. To evaluate the clinical efficacy and safety of intra-articular injection with pure platelet-rich plasma (P-PRP) versus those of leukocyte platelet-rich plasma (L-PRP) in treating knee cartilage lesions, we conducted a double-blind, randomized controlled clinical trial with a larger sample and longer follow-up period.

Culture of Mesenchymal Stem Cells Derived From the Infrapatellar Fat Pad Without Enzyme and Preliminary Study on the Repair of Articular Cartilage Defects in Rabbits.

The aim of the study was to evaluate the advantages of without enzyme isolating patellar fat pad-derived mesenchymal stem cells (IPFP-SCs) and the feasibility of cartilage repair. The IPFP-SCs were isolated using the without enzyme method and compared with the IPFP-SCs obtained by the traditional enzyme digestion method in terms of cell proliferation ability, characterization, and differentiation ability, and the differences in chondrogenic induction and differentiation between the two groups were compared. Twenty-four New Zealand rabbits were randomly divided into four groups ( = 6).

An alternative method for personalized tourniquet pressure in total knee arthroplasty: a prospective randomized and controlled study.

Tourniquet use always carries potential risks, which can range from mild transient functional impairments of thigh pain, skin blisters to severe permanent dysfunction of limb paralysis, nerve injuries or compartment syndrome. The ideal method for minimizing intraoperative tourniquet pressure (TP) for reducing postoperative complications remains controversial. In this prospective, randomized and controlled study, we reinvestigated an estimation formula for TP based on thigh circumferences and systolic blood pressure (SBP) with two traditional methods for TP determination in total knee arthroplasty (TKA): SBP plus 100 mmHg and a fixed value of 300 mmHg.

Oct4 facilitates chondrogenic differentiation of mesenchymal stem cells by mediating CIP2A expression.

Bone development and cartilage formation require strict modulation of gene expression for mesenchymal stem cells (MSCs) to progress through their differentiation stages. Octamer-binding transcription factor 4 (Oct4) expression is generally restricted to developing embryonic pluripotent cells, but its role in chondrogenic differentiation (CD) of MSCs remains unclear. We therefore investigated the role of Oct4 in CD using a microarray, quantitative real-time polymerase chain reaction, and western blotting.

Decellularized extracellular matrix loaded with IPFP-SC for repairing rabbit osteochondral defects.

Background: Tissue engineering is widely applied to treat osteochondral damage in osteoarthritis (OA). However, the superposition of seed cells, material scaffolds, inducing factors, and microenvironmental factors limit their practical application. We intended to develop a novel tissue engineering method for improving the repairment of osteochondral damage and to discuss its effect on repairing osteochondral defects.

Synergic adhesive chemistry-based fabrication of BMP-2 immobilized silk fibroin hydrogel functionalized with hybrid nanomaterial to augment osteogenic differentiation of rBMSCs for bone defect repair.

Bone defect repair and tissue engineering is specifically challenging process because of the distinctive morphological and structural behaviours of natural bone with complex healing and biochemical mechanisms. In the present investigation, we designed dopamine adhesive chemistry-based fabrication of silk fibroin hydrogel (SFD) with incorporation of nano-hydroxyapatite (nHA)-graphene oxide (GO) hybrid nanofillers with well-arranged porous morphology immobilized with bone morphogenic protein-2 (BMP-2) for the effective in vitro rabbit bone marrow derived mesenchymal stem cells loading compatibility and in vivo new bone regrowth and collagen deposition ability. We have achieved bone-specific hydrogel scaffolds with upgraded structural features, mechanical properties and particularly promoted in vitro osteogenic differentiation and compatibility of rabbit bone marrow mesenchymal stem cells (rBMSCs).

Comparison between Intra-Articular Injection of Infrapatellar Fat Pad (IPFP) Cell Concentrates and IPFP-Mesenchymal Stem Cells (MSCs) for Cartilage Defect Repair of the Knee Joint in Rabbits.

Mesenchymal stem cells (MSCs) have emerged as a promising therapeutic method in regenerative medicine. Our previous research adopted a simple nonenzymatic strategy for the preparation of a new type of ready-to-use infrapatellar fat pad (IPFP) cell concentrates. The aim of this study was to compare the therapeutic efficacy of intra-articular (IA) injection of autologous IPFP cell concentrates and allogeneic IPFP-MSCs obtained from these concentrates in a rabbit articular cartilage defect model.

Fibrin Glue-Kartogenin Complex Promotes the Regeneration of the Tendon-Bone Interface in Rotator Cuff Injury.

Objective: Rotator cuff injury healing is problematic because the tendon-bone junction often forms cicatricial tissues, rather than fibrocartilage, which leads to mechanical impairment and is prone to redamage. Kartogenin (KGN) is a newly discovered small molecule compound which can induce cartilage formation through chondrogenesis of endogenous mesenchymal stem cells.

Methods: In this study, we used KGN with fibrin glue (FG) to repair the rotator cuff injury by promoting the formation of fibrocartilage at the tendon to bone interface.

Exosomes from Kartogenin-Pretreated Infrapatellar Fat Pad Mesenchymal Stem Cells Enhance Chondrocyte Anabolism and Articular Cartilage Regeneration.

Objective: To evaluate the effect of Kartogenin-pretreated exosomes derived from infrapatellar fat pad mesenchymal stem cells on chondrocyte in vitro and articular cartilage regeneration in vivo.

Methods: Infrapatellar fat pad mesenchymal stem cells (IPFP-MSCs) were isolated from rabbits to harvest exosomes. After identification of mesenchymal stem cells and exosomes, rabbit chondrocytes were divided into three groups for further treatment: the EXO group (chondrocytes treated with exosomes isolated from infrapatellar fat pad mesenchymal stem cells), KGN-EXO group (chondrocytes treated with exosomes isolated from infrapatellar fat pad mesenchymal stem cells pretreated with KGN), and control group.

Regulating effect of Circ_ATRNL1 on the promotion of SOX9 expression to promote chondrogenic differentiation of hAMSCs mediated by MiR-145-5p.

Circ_ATRNL1 is significantly highly expressed in cartilage tissues of patients with osteoarthritis. This study explored the role and mechanism of circ_ATRNL1 in cartilage differentiation of human adipose-derived mesenchymal stem cells (hAMSCs). hAMSCs were isolated and identified by flow cytometry.

The clinical efficacy of arthroscopic therapy with knee infrapatellar fat pad cell concentrates in treating knee cartilage lesion: a prospective, randomized, and controlled study.

Introduction: To evaluate the clinical efficacy of arthroscopic therapy with infrapatellar fat pad cell concentrates in treating knee cartilage lesions, we conducted a prospective randomized single-blind clinical study of controlled method.

Methods: Sixty cases from Shanghai Changzheng Hospital from April 2018 to December 2019 were chosen and randomly divided into 2 groups equally. Patients in the experiment group were treated through knee arthroscopy with knee infrapatellar fat pad cell concentrates containing mesenchymal stromal cells, while patients in the control group were treated through regular knee arthroscopic therapy.

LINC02288 promotes chondrocyte apoptosis and inflammation through miR-374a-3p targeting RTN3.

Background: Dysregulation of long non-coding RNAs (lncRNAs) is related to the occurrence of osteoarthritis (OA). In the present study, we explored the role of LINC02288 and its regulatory mechanism in OA development.

Methods: GSE113825 was obtained from Gene Expression Omnibus (GEO) database and analyzed to identify the differentially expressed lncRNAs in OA.

Over-expression of MEG3 promotes differentiation of bone marrow mesenchymal stem cells into chondrocytes by regulating miR-129-5p/RUNX1 axis.

This study explored the role of MEG3 in the cartilage differentiation of bone marrow mesenchymal stem cells (BMSCs). We investigated the effects of over-expression and knockdown of MEG3 on cell viability, cell differentiation, and the expressions of MEG3, miR-129-5p, COL2, chondrocyte differentiation-related genes (sry-type high-mobility-group box 9 (SOX9), SOX5, Aggrecan, silent information regulator 1 (SIRT1), and Cartilage oligomeric matrix protein (COMP)). The targeting relationship between MEG3 and miR-129-5p and the target gene of miR-129-5p was confirmed through Starbase, TargetScan and luciferase experiments.

CircADAMTS6/miR-431-5p axis regulate interleukin-1β induced chondrocyte apoptosis.

Background: Growing evidence suggests that circular RNAs (circRNAs) are involved in the development of osteoarthritis (OA). The present study aimed to explore the CircADAMTS6/miR-431-5p axis with respect to regulating interleukin-1β (IL-1β) induced chondrocyte apoptosis.

Methods: We first evaluated the differentially expressed circRNAs between normal chondrocytes and interleukin (IL)-1β-stimulated chondrocytes.

The mineralization, drug release and bone defect repair properties of calcium phosphates/PLA modified tantalum scaffolds.

Calcium phosphate based biomaterials have been widely studied in biomedical areas. Herein, amorphous calcium phosphate (ACP) nanospheres and hydroxyapatite (HA) nanorods were separately prepared and used for coating tantalum (Ta) scaffolds with a polymer of polylactide (PLA). We have found that different crystal phases of calcium phosphate coated on Ta scaffolds displayed different effects on the surface morphologies, mineralization and bovine serum albumin (BSA) release.

Is soft tissue repair a right choice to avoid early dislocation after THA in posterior approach?

Background: Dislocation is the second most common complication after total hip arthroplasty (THA). The effectiveness of soft tissue repair to reduce dislocation rate is still debated and thus a meta-analysis was conducted.

Methods: A systematic search in PubMed, Embase, and Cochrane databases was conducted for this meta-analysis.

Simplified Chinese version of the Forgotten Joint Score (FJS) for patients who underwent joint arthroplasty: cross-cultural adaptation and validation.

Background: The Forgotten Joint Score (FJS) is a newly developed health-related quality of life (HRQoL) questionnaire designed to evaluate the awareness after total knee arthroplasty (TKA). This study cross-culturally adapted and psychometrically validated a simplified Chinese version of the FJS (SC-FJS).

Methods: Cross-cultural adaptation was performed according to the internationally recognized guidelines.

Electrospinning of calcium phosphate-poly (d,l-lactic acid) nanofibers for sustained release of water-soluble drug and fast mineralization.

Calcium phosphate-based biomaterials have been well studied in biomedical fields due to their outstanding chemical and biological properties which are similar to the inorganic constituents in bone tissue. In this study, amorphous calcium phosphate (ACP) nanoparticles were prepared by a precipitation method, and used for preparation of ACP-poly(d,l-lactic acid) (ACP-PLA) nanofibers and water-soluble drug-containing ACP-PLA nanofibers by electrospinning. Promoting the encapsulation efficiency of water-soluble drugs in electrospun hydrophobic polymer nanofibers is a common problem due to the incompatibility between the water-soluble drug molecules and hydrophobic polymers solution.

Amorphous calcium phosphate, hydroxyapatite and poly(d,l-lactic acid) composite nanofibers: Electrospinning preparation, mineralization and in vivo bone defect repair.

Due to the outstanding bioactivity and biocompatibility, calcium phosphate (CaP) based materials have been widely investigated for applications in the biomedical fields. In this study, amorphous calcium phosphate (ACP) nanospheres and hydroxyapatite (HA) nanorods have been prepared and hybridized with poly(d,l-lactic acid) (PLA) to fabricate the composite nanofibers through electrospinning. The as-prepared ACP-PLA and HA-PLA composite nanofibers exhibit favorable mineralization behaviors in simulated body fluid (SBF).

Association of PPARγ gene polymorphisms with osteoarthritis in a southeast Chinese population.

Primary osteoarthritis (OA) is a leading cause of disability in developed countries. Currently no satisfactory treatment to stop disease progression exists. Recent studies suggest that activation of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) is an interesting therapeutic target for this disease.