Publications by authors named "H Weinans"

320 Publications

IL4-10 Fusion Protein Shows DMOAD Activity in a Rat Osteoarthritis Model.

Cartilage 2021 Jun 23:19476035211026736. Epub 2021 Jun 23.

Department of Rheumatology & Clinical Immunology, University Medical Center Utrecht, Utrecht University, Utrecht, The Netherlands.

Objective: Ideally, disease-modifying osteoarthritis (OA) drugs (DMOAD) should combine chondroprotective, anti-inflammatory, and analgesic effects in a single molecule. A fusion protein of interleukin-4 (IL-4) and IL-10 (IL4-10 FP) possesses these combined effects. In this study, the DMOAD activity of rat IL4-10 FP (rIL4-10 FP) was tested in a rat model of surgically induced OA under metabolic dysregulation.

Design: rIL4-10 FP was produced with HEK293F cells. Bioactivity of purified rIL4-10 FP was determined in a whole blood assay. Male Wistar rats ( = 20) were fed a high-fat diet (HFD) to induce metabolic dysregulation. After 12 weeks, OA was induced according to the Groove model. Two weeks after OA induction, rats were randomly divided into 2 groups and treated with 10 weekly, intra-articular injections of either rIL4-10 FP ( = 10) or phosphate buffered saline (PBS; = 10). Possible antibody formation was evaluated using ELISA, cartilage degeneration and synovial inflammation were evaluated by histology and mechanical allodynia was evaluated using the von Frey test.

Results: Intra-articular injections with rIL4-10 FP significantly reduced cartilage degeneration ( = 0.042) and decreased mechanical allodynia ( < 0.001) compared with PBS. Only mild synovial inflammation was found (nonsignificant), limiting detection of putative anti-inflammatory effects. Multiple injections of rIL4-10 FP did not induce antibodies against rIL4-10 FP.

Conclusion: rIL4-10 FP showed chondroprotective and analgesic activity in a rat OA model with moderate cartilage damage, mild synovial inflammation, and pain. Future studies will need to address whether less frequent intra-articular injections, for example, with formulations with increased residence time, would also lead to DMOAD activity.
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http://dx.doi.org/10.1177/19476035211026736DOI Listing
June 2021

Regenerating Critical Size Rat Segmental Bone Defects with a Self-Healing Hybrid Nanocomposite Hydrogel: Effect of Bone Condition and BMP-2 Incorporation.

Macromol Biosci 2021 Jun 12:e2100088. Epub 2021 Jun 12.

Biomaterials, Radboudumc, Philips van Leijdenlaan 25, Nijmegen, Gelderland, 6525 EX, The Netherlands.

The aim of the current study is to assess the biological performance of self-healing hydrogels based on calcium phosphate (CaP) nanoparticles and bisphosphonate (BP) conjugated hyaluronan (HA) in a critical size segmental femoral bone defect model in rats. Additionally, these hydrogels are loaded with bone morphogenetic protein 2 (BMP-2) and their performance is compared in healthy and osteoporotic bone conditions. Treatment groups comprise internal plate fixation and placement of a PTFE tube containing hydrogel (HA -CaP) or hydrogel loaded with BMP-2 in two dosages (HA -CaP-lowBMP2 or HA -CaP-highBMP2). Twelve weeks after bone defect surgery, bone formation is analyzed by X-ray examination, micro-CT analysis, and histomorphometry. The data show that critical size, segmental femoral bone defects cannot be healed with HA -CaP gel alone. Loading of the HA -CaP gel with low dose BMP-2 significantly improve bone formation and resulted in defect bridging in 100% of the defects. Alternatively, high dose BMP-2 loading of the HA -CaP gel does not improve bone formation within the defect area, but leads to excessive bone formation outside the defect area. Bone defect healing is not affected by osteoporotic bone conditions.
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http://dx.doi.org/10.1002/mabi.202100088DOI Listing
June 2021

The role of the femoral component orientation on dislocations in THA: a systematic review.

Arch Orthop Trauma Surg 2021 Jun 8. Epub 2021 Jun 8.

Department of Orthopedics, Diakonessenhuis, Utrecht, Zeist, The Netherlands.

Introduction: Dislocation remains a major complication in total hip arthroplasty (THA), in which femoral component orientation is considered a key parameter. New imaging modalities and definitions on femoral component orientation have been introduced, describing orientation in different planes. This study aims to systematically review the relevance of the different orientation parameters on implant stability.

Methods: A systematic review was performed according to the PRISMA guidelines to identify articles in the PubMed and EMBASE databases that study the relation between any femoral component orientation parameters and implant stability in primary THA.

Results: After screening for inclusion and exclusion criteria and quality assessment, nine articles were included. Definitions to describe the femoral component orientation and methodologies to assess its relevance for implant stability differed greatly, with lack of consensus. Seven retrospective case-control studies reported on the relevance of the transversal plane orientation: Low femoral- or low combined femoral and acetabular anteversion was statistical significantly related with more posterior dislocations, and high femoral- or combined femoral and acetabular anteversion with anterior dislocations in two studies. There were insufficient data on sagittal and coronal component orientation in relation to implant stability.

Conclusion: Because of incomparable definitions, limited quality and heterogeneity in methodology of the included studies, there is only weak evidence that the degree of transverse component version is related with implant stability in primary THA. Recommendations about the optimal orientation of the femoral component in all three anatomical planes cannot be provided. Future studies should uniformly define the three-dimensional orientation of the femoral component and systematically describe implant stability.
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http://dx.doi.org/10.1007/s00402-021-03982-1DOI Listing
June 2021

One-year infection control rates of a DAIR (debridement, antibiotics and implant retention) procedure after primary and prosthetic-joint-infection-related revision arthroplasty - a retrospective cohort study.

J Bone Jt Infect 2021 27;6(4):91-97. Epub 2021 Jan 27.

Department of Orthopedics, University Medical Center Utrecht, Utrecht, the Netherlands.

: Debridement, antibiotics and implant retention (DAIR) procedures are effective treatments for acute postoperative or acute hematogenous periprosthetic joint infections. However, literature reporting on the effectiveness of DAIR procedures performed after a one- or two-stage revision because of a prosthetic joint infection (PJI) (PJI-related revision arthroplasty) is scarce. The aim of this study is to retrospectively evaluate the infection control after 1 year of a DAIR procedure in the case of an early postoperative infection either after primary arthroplasty or after PJI-related revision arthroplasty. : All patients treated with a DAIR procedure within 3 months after onset of PJI between 2009 and 2017 were retrospectively included. Data were collected on patient and infection characteristics. All infections were confirmed by applying the Musculoskeletal Infection Society (MSIS) 2014 criteria. The primary outcome was successful control of infection at 1 year after a DAIR procedure, which was defined as the absence of clinical signs, such as pain, swelling, and erythema; radiological signs, such as protheses loosening; or laboratory signs, such as C-reactive protein (CRP) ( ) with no use of antibiotic therapy. : Sixty-seven patients were treated with a DAIR procedure (41 hips and 26 knees). Successful infection control rates of a DAIR procedure after primary arthroplasty ( ) and after prior PJI-related revision arthroplasty ( ) were 69 % and 56 %, respectively ( ). The successful infection control rates of a DAIR procedure after an early acute infection ( ) and after a hematogenous infection ( ) following primary arthroplasty were both 69 % ( ). : In this limited study population, no statistically significant difference is found in infection control after 1 year between DAIR procedures after primary arthroplasty and PJI-related revision arthroplasty.
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http://dx.doi.org/10.5194/jbji-6-91-2021DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8129908PMC
January 2021

Topographic features of nano-pores within the osteochondral interface and their effects on transport properties -a 3D imaging and modeling study.

J Biomech 2021 Jun 11;123:110504. Epub 2021 May 11.

Department of Orthopaedics, University Medical Centre Utrecht, Utrecht, the Netherlands; Department of Biomechanical Engineering, Faculty of Mechanical, Maritime and Materials Engineering, Delft University of Technology, Delft, the Netherlands.

Recent insights suggest that the osteochondral interface plays a central role in maintaining healthy articulating joints. Uncovering the underlying transport mechanisms is key to the understanding of the cross-talk between articular cartilage and subchondral bone. Here, we describe the mechanisms that facilitate transport at the osteochondral interface. Using scanning electron microscopy (SEM), we found a continuous transition of mineralization architecture from the non-calcified cartilage towards the calcified cartilage. This refurbishes the classical picture of the so-called tidemark; a well-defined discontinuity at the osteochondral interface. Using focused-ion-beam SEM (FIB-SEM) on one osteochondral plug derived from a human cadaveric knee, we elucidated that the pore structure gradually varies from the calcified cartilage towards the subchondral bone plate. We identified nano-pores with radius of 10.71 ± 6.45 nm in calcified cartilage to 39.1 ± 26.17 nm in the subchondral bone plate. The extracted pore sizes were used to construct 3D pore-scale numerical models to explore the effect of pore sizes and connectivity among different pores. Results indicated that connectivity of nano-pores in calcified cartilage is highly compromised compared to the subchondral bone plate. Flow simulations showed a permeability decrease by about 2000-fold and solute transport simulations using a tracer (iodixanol, 1.5 kDa with a free diffusivity of 2.5 × 10 m/s) showed diffusivity decrease by a factor of 1.5. Taken together, architecture of the nano-pores and the complex mineralization pattern in the osteochondral interface considerably impacts the cross-talk between cartilage and bone.
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http://dx.doi.org/10.1016/j.jbiomech.2021.110504DOI Listing
June 2021