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Bone & Joint Research
Vol. 13, Issue 12 | Pages 725 - 740
5 Dec 2024
Xing J Liu S

Addressing bone defects is a complex medical challenge that involves dealing with various skeletal conditions, including fractures, osteoporosis (OP), bone tumours, and bone infection defects. Despite the availability of multiple conventional treatments for these skeletal conditions, numerous limitations and unresolved issues persist. As a solution, advancements in biomedical materials have recently resulted in novel therapeutic concepts. As an emerging biomaterial for bone defect treatment, graphene oxide (GO) in particular has gained substantial attention from researchers due to its potential applications and prospects. In other words, GO scaffolds have demonstrated remarkable potential for bone defect treatment. Furthermore, GO-loaded biomaterials can promote osteoblast adhesion, proliferation, and differentiation while stimulating bone matrix deposition and formation. Given their favourable biocompatibility and osteoinductive capabilities, these materials offer a novel therapeutic avenue for bone tissue regeneration and repair. This comprehensive review systematically outlines GO scaffolds’ diverse roles and potential applications in bone defect treatment. Cite this article: Bone Joint Res 2024;13(12):725–740


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 83 - 83
14 Nov 2024
Llucia A Espinosa SC
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Introduction. Tendon ruptures represent one of the most common acute tendon injuries in adults worldwide, affecting millions of people anually and becoming more prevalent due to longer life expectancies and sports activities. Current clinical treatments for full tears are unable to completely restore the torn tendons to their native composition, structure and mechanical properties. To address this clinical challenge, tissue-engineered substitutes will be developed to serve as functional replacements for total tendon ruptures that closely resemble the original tissue, restoring functionality. Method. Water borne polyurethanes (WBPU) containing acrylate groups, specifically polyethylene glycol methacrylate (PEGMA) or 2-hydroxyethyl methacrylate (HEMA), were combined with mouse mesenchymal stem cells (MoMSCs) and heparin sodium to formulate bioinks for the fabrication of scaffolds via extrusion-based 3D bioprinting. Result. The biocompatibility of acrylated-WBPUs was confirmed in 2D with MoMSCs using lactate dehydrogenase assay, DNA assay and live/dead assays. Cell-laden scaffolds were 3D-bioprinted by encapsulating MoMSCs at varying cell densities within the acrylated WBPUs. The resulting 3D structures support cell viability and proliferation within the scaffolds, as confirmed by live/dead assay, lactate dehydrogenase assay and DNA assays. Differentiation studies in the 3D-bioprinted scaffolds demonstrated the phenotype transition of MoMSCs toward tenocytes through gene expression and protein deposition analysis. The inclusion of sodium heparin in the bioinks revealed increased synthesis of matrix assembly proteins within the 3D-bioprinted constructs. Conclusion. The developed bioinks were biocompatible and printable, supporting cell viability within the 3D-bioprinted scaffold. The fabricated cell-laden constructs sustained cell proliferation, differentiation, and tissue formation. The addition of heparin sodium enhanced tissue formation and organization, showing promising results for the regeneration of tendon total ruptures. Principio del formularioThis work was supported by the Spanish State Research Agency (AEI) under grant No CPP2021-008754. The authors would like to thank their partners in the project, which are in charge of the synthesis of heparin sodium and acrylated-WBPUs


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 95 - 95
14 Nov 2024
Machain TC Kharchenko A Hostettler R Lippl J Mouthuy PA
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Introduction. Supraspinatus tears comprise most rotator cuff injuries, the leading cause of shoulder pain and an increasing problem with ageing populations. Surgical repair of considerable or persistent damages is customary, although not invariably successful. Tissue engineering presents a promising alternative to generate functional tissue constructs with improved healing capacities. This study explores tendon tissue constructs’ culture in a platform providing physiological mechanical stimulation and reports on the effect of different loading regimes on the viability of human tendon cells. Method. Porcine decellularized tendon scaffolds were fixed into flexible, self-contained bioreactor chambers, seeded with human tenocytes, allocated in triplicates to either static control, low (15±0.8Newtons [N]), medium (26±0.5N), or high (49±2.1N)-force-regime groups, connected to a perfusion system and cultured under standard conditions. A humanoid robotic arm provided 30-minute adduction/abduction stimulation to chambers daily over a week. A metabolic activity assay served to assess cell viability at four time points. Statistical significance = p<0.05. Result. One day after beginning mechanical stimulation, chambers in the medium and high-force regimes displayed a rise in metabolic activity by 3% and 5%, respectively. By the last experimental day, all mechanical stimulation regimes had induced an augment in cell viability (15%, 57% and 39% with low, medium, and high loads, respectively) matched against the static controls. Compared to all other conditions, the medium-force regime prompted an increased relative change in metabolic activity for every time point set against day one (p<0.05). Conclusion. Human tenocytes’ viability reflected by metabolic activity in a physiologically relevant bioreactor system is enhanced by loading forces around 25N when mechanically stimulating using adduction/abduction motions. Knowing the most favourable load regime to stimulate tenocyte growth has informed the ongoing exploration of the distinctive effect of different motions on tendon regeneration towards engineering tissue grafts. This work was supported by the Engineering and Physical Sciences Research Council EP/S003509/1


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 91 - 91
14 Nov 2024
Bai L Yin Z
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Introduction. Herein, a tri-layered core-shell microfibrous scaffold with layer-specific growth factors (GFs) release is developed using coaxial electrohydrodynamic (EHD) printing for in situ cell recruitment and differentiation to facilitate gradient enthesis tissue repair. Our findings suggest that the microfibrous scaffolds with layer-specific GFs release may offer a promising clinical solution for enthesis regeneration. Method. Utilizing coaxial electrohydrodynamic (EHD) printing, we engineered tri-layered core-shell microfibrous scaffolds, each layer tailored with specific growth factors (GFs) for targeted enthesis tissue repair. This configuration aims to sequentially guide cell migration and differentiation, mirroring the natural enthesis’ gradient structure. SDF-1 was strategically loaded into the shell, while bFGF, TGF-β, and BMP-2 were encapsulated in the core, each selected for their roles in stimulating the regeneration of corresponding enthesis tissue layers. Result. The coaxial EHD-printed microfibrous scaffolds demonstrated a core-shell fiber width of 24.3 ± 6.3 μm, supporting distinct tenogenic, chondrogenic, and osteogenic layers with pore sizes of 81.5 ± 4.6 μm, 173.3 ± 6.9 μm, and 388.9 ± 6.9 μm, respectively. This structure facilitated a targeted and effective release of growth factors, optimizing stem cell recruitment and differentiation. In vivo assessments demonstrated that the scaffolds significantly enhanced biomechanical properties and facilitated the formation of gradient enthesis structures, with improved biomechanical strength approximately 2-3 times that of control groups. These results highlight the scaffold's capability to mimic the native enthesis structure, encouraging a conducive environment for cell-mediated repair and regeneration. Conclusion. The integration of layer-specific growth factors not only fostered a conducive environment for tissue regeneration but also exemplified a leap in the design of scaffolds that closely mimic the native tendon-to-bone interface. The findings illuminate the scaffold's capacity to direct cellular behavior and tissue formation, heralding a new era in regenerative strategies and offering a promising avenue for clinical translation in the treatment of rotator cuff injuries


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 111 - 111
14 Nov 2024
Torre ID Redondo LM Sierra CG Cabello JCR Bsarcia AJA
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Introduction. The objective of the work is construction of a multi-bioactive scaffold based on that allows a space/time control over the regeneration of damaged bones by Medication-Related Osteonecrosis of the Jaw using a minimal invasive approach based on the injection of the fast-degrading pro neuro and angiogenic ELR (Elastin-Like Recombinamers) based hydrogels. Method. Chemical crosslinking facilitated the creation of multi-bioactive scaffolds using ELRs with reactive groups. Cell-loaded multi-bioactive scaffolds, prepared and incubated, underwent evaluation for adhesion, proliferation, angiogenic, and neurogenic potential. In vitro assessments utilized immunofluorescence staining and ELISA assays, while live-recorded monitoring and live-dead analysis ensured cytocompatibility. In rat and rabbit models, preformed scaffolds were subcutaneously implanted, and the regenerative process was evaluated over time. Rabbit models with MRONJ underwent traditional or percutaneous implantation, with histological evaluation following established bone histological techniques. Result. A 3D scaffold using ELR that combines various peptides with different degradation rates to guide both angiogenesis and neurogenesis has been developed. Notably, scaffolds with different degradation rates promoted distinct patterns of vascularization and innervation, facilitating integration with host tissue. This work demonstrates the potential for tailored tissue engineering, where the scaffold's bioactivities and degradation rates can control angiogenesis and neurogenesis. In an animal model of medication-related osteonecrosis of the jaw (MRONJ), the scaffold showed promising results in promoting bone regeneration in a necrotic environment, as confirmed by histological and imaging analyses. This study opens avenues for novel tissue-engineering strategies where precise control over vascularization and nerve growth is crucial. Conclusion. A groundbreaking dual approach, simultaneously targeting angiogenesis and innervation, addresses the necrotic bone in MRONJ syndrome. Vascularization and nerve formation play pivotal roles in driving reparative elements for bone regeneration. The scaffold achieves effective time/space control over necrotic bone regeneration. The authors are grateful for funding from the Spanish Government (PID2020-118669RA-I00)


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 82 - 82
14 Nov 2024
Kühl J Grocholl J Seekamp A Klüter T Fuchs S
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Introduction. The surgical treatment of critical-sized bone defects with complex three-dimensional (3D) geometries is a challenge for the treating surgeon. Additive manufacturing such as 3D printing enables the production of highly individualized bone implants meeting the shape of the patient's bone defect and including a tunable internal structure. In this study, we showcase the design process for patient-specific implants with critical-sized tibia defects. Methods. Two clinical cases of patients with critical tibia defects (size 63×20×21 mm and 50×24×17 mm) were chosen. Brainlab software was used for segmentation of CT data generating 3D models of the defects. The implant construction involves multiple stages. Initially, the outer shell is precisely defined. Subsequently, the specified volume is populated with internal structures using Voronoi, Gyroid, and NaCl crystal structures. Variation in pore size (1.6 mm and 1.0 mm) was accomplished by adjusting scaffold size and material thickness. Results. An algorithmic design process in Rhino and Grasshopper was successfully applied to generate model implants for the tibia from Ct data. By integrating a precise mesh into an outer shell, a scaffold with controlled porosity was designed. In terms of the internal design, both Voronoi and Gyroid form macroscopically homogeneous properties, while NaCl, exhibits irregularities in density and consequently, in the strength of the structure. Data implied that Voronoi and Gyroid structures adapt more precisely to complex and irregular outer shapes of the implants. Conclusion. In proof-of-principle studies customized tibia implants were successfully generated and printed as model implants based on resin. Further studies will include more patient data sets to refine the workflows and digital tools for a broader spectrum of bone defects. The algorithm-based design might offer a tremendous potential in terms of an automated design process for 3D printed implants which is essential for clinical application


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 85 - 85
14 Nov 2024
Florit MG Graça AL Domingues RMA Gomes MME
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Introduction. Healthy tendons are mainly composed of aligned collagen hierarchically organized from collagen fibrils to fiber bundles with a scarce cellular population mainly composed of tenocytes and tendon stem/progenitor cells. However, injured tendon acquires a fibrotic state characterized by a loss of ECM alignment and increased cellularization. The lack of reliable 3D models that recreate the organization and microenvironment of healthy and diseased tendons is one of the main obstacles faced by the scientific community. Method. To recreate the architecture of healthy and diseased tendons, electrospun nanofiber scaffolds with anisotropic and isotropic nanotopography were developed. These scaffolds were coated with a shell consisting of cell-laden hydrogels encapsulating human adipose-derived stem cells (hASCs) to include the living component. To show the versatility of the system, extracellular vesicles (EVs) were encapsulated in the hydrogel as biological cues. The living fibers were characterized by microscopy and morphological analysis. The morphology and phenotype of cells was evaluated using microscopy, gene expression analysis and immunostainings for tendon markers. Results. Scaffolds mimicked the native hierarchical structure of tendons and size of tendon fascicles. hASCs showed high elongation and cytoskeleton anisotropic organization, typical of tenocytes. Moreover, the bioengineered living fibers supported the tenogenic differentiation of stem cells over time, as indicated by the sustained expression of tenogenic and extracellular matrix markers. Finally, the hydrogel layer acted not only as a hydrated biomimetic environment adequate for cell encapsulation but also as a carrier and delivery system of EVs to cells, which improved their tenogenic commitment. Conclusion. We bioengineered composite living fibers made of hierarchically organized electrospun fibers, coated with hydrogel encapsulating hASCs and biofunctional EVs. These provide an in vitro system to recreate tendon, allowing for the study of the effects of biophysical cues in tendon microenvironments and the influence of biologics on cells behavior. Acknowledgments. CP21/00136, PI22/01686, CA22170, 10.54499/2020.03410.CEECIND/CP1600/CT0013, 10.54499/2022.05526.PTDC


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 11 - 11
14 Nov 2024
Maia J Bilo M Silva AS Sobreiro-Almeida R Mano J
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Introduction. Ink engineering can advance 3D-printability for better therapeutics, with optimized proprieties. Herein, we describe a methodology for yielding 3D-printable nanocomposite inks (NC) using low-viscous matrices, via the interaction between the organic and inorganic phases by chemical coupling. Method. Natural photocurable matrices were synthesized: a protein – bovine serum albumin methacrylate (BSAMA), and a polysaccharide – hyaluronic acid methacrylate (HAMA). Bioglass nanoparticles (BGNP) were synthesized and functionalized via aminosilane chemistry. The functionalization of BSAMA, HAMA, and BGNP were quantified via NMR. To arise extrudable inks, 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDC) and N-Hydroxysuccinimide (NHS) chemistry was used to link innate carboxylic groups of BSAMA/HAMA and amine-functionalized BGNP. Different crosslinker and BGNP amounts were tested. Visible light photopolymerization is performed, using lithium phenyl-2,4,6-trimethylbenzoylphosphinate. The NC's rheological, mechanical, and biological behavior was evaluated before 3D extrusion printability. Result. All composite formulations effectively immobilized and homogeneously dispersed the BGNP, turning low-viscous materials (< 1 Pa) into shear-thinning formulations with tunable increased elastic/viscous moduli (50-500 Pa). More pronounced increments were found with increasing EDC/NHS and BGNP concentrations. The resulting inks produce robust and stable scaffolds successfully retrieved after post-print photocrosslinking (1-5 kPa). Bioactivity in simulated body fluid and in vitro assays using adipose-derive stem cells revealed a similar calcium/phosphate ratio to that of hydroxyapatite, and increased viability and metabolic activity. BSAMA and HAMA demonstrated distinct natures not only in printability but also in overall cellular performance and mechanical properties, making these ideal for interfacial tissue engineering. Conclusion. This strategy demonstrated being effective and reproducible to advance nanocomposites for 3D printing using different types of biomaterials. Further, we envision using both inks to produce hierarchical constructs via extrusion printing, better mimicking bone-to-cartilage interfaces. Acknowledgements. FCT grants (DOI:10.54499/2022.04605.CEECIND/CP1720/CT0021), (BI/UI89/10303/2022), (PRT/BD/154735/2023); EU's Horizon 2020 research and innovation programs InterLynk (Nº953169) and SUPRALIFE (Nº101079482) projects; CICECO-Aveiro Institute of Materials projects (DOI:10.54499/UIDB/50011/2020), (DOI:10.54499/UIDP/50011/2020), and (DOI:10.54499/LA/P/0006/2020), financed by FCT/MCTES(PIDDAC)


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 14 - 14
14 Nov 2024
Gögele CL Fleischmann N Müller S Liesenberg T Pizzadili G Wiltzsch S Gerdes T Schaefer-Eckart K Lenhart A Schulze-Tanzil G
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Introduction. Articular cartilage has a low self-regeneration capacity. Cartilage defects have to be treated to minimize the risk of the onset of osteoarthritis. Bioactive glass (BG) is a promising source for cartilage tissue engineering. Until now, conventional BGs (like BG1393) have been used, mostly for bone regeneration, as they are able to form a hydroxyapatite layer and are therefore, less suited for cartilage reconstruction. The aim of this study is to study the effect of 3D printed hydrogel scaffolds supplemented with spheres of the BG CAR12N to improve the chondrogenesis of mesenchymal stem cells (MSCs). Method. Based on our new glass composition (CAR12N), small BG spheres (25-40 µm) were produced and mixed with hydrogel and primary human (h) MSCs. Grid printed scaffolds were cultivated up to 21 days in expansion or chondrogenic differentiation medium. Macroscopical images of the scaffolds were taken to observe surface changes. Vitality, DNA and sulfated glycosaminoglycan (GAG) content was semiquantitatively measured as well as extracellular matrix gene transcription. Result. It was possible to print grid shaped hydrogel scaffolds with BG spheres and hMSCs. No significant changes in scaffold shape, surface or pore size were detected after 21 days in culture. The BG spheres were homogeneously distributed inside the grids. Vitality was significantly higher in grids with CAR12N spheres in comparison to those without. The DNA content remained constant over three weeks, but was higher in the sphere containing scaffolds than in those without BG spheres. GAG content in the grids increased not only with additional cultivation time but especially in grids with BG spheres in chondrogenic medium. Aggrecan and type II collagen gene expression was significantly higher grids cultured in the chondrogenic differentiation medium. Conclusion. This developed 3D model, is very interesting to study the effect of BG on hMSCs and to understand the influence of leaking ions on chondrogenesis


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 26 - 26
14 Nov 2024
Tiplady S Heinemann C Kruppke B Manda K Clarke S Lennon A Larrañeta E Buchanan F
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Introduction. The incidences of fragility fractures, often because of osteoporosis, are increasing. Research has moved towards bioresorbable scaffolds that provide temporary mechanical stability and promote osteogenesis. This research aims to fabricate a 3D printed composite Poly (l-lactic-co-glycolic acid)-strontium doped tricalcium phosphate (PLGA-SrTCP) scaffold and evaluate in an in vitro co culture study containing osteoporotic donor cells. Method. PLGA, PLGA TCP, and PLGA SrTCP scaffolds were produced using Fused Filament Fabrication (FFF). A four-group 35-day cell culture study was carried out using human bone marrow derived mesenchymal stem cells (hMSCs) from osteoporotic and control donors (monoculture) and hMSCs & human monocytes (hMCs) (Co culture). Outcome measures were biochemical assays, PCR, and cell imaging. Cells were cultured on scaffolds that had been pre-degraded for six weeks at 47°C prior to drying and gamma sterilisation. Result. 3D printed scaffolds were successfully produced by FFF. All groups in the study supported cell attachment onto the scaffolds, producing extracellular matrices as well as evidence of osteoclast cell structures. Osteoporotic cells increased CTSK activity and CAII activity and decreased ALP activity compared to controls. In control cultures, the addition of bTCP and bTCP/Sr to the PLGA reduced TRAP5b, CAII and ALP activity compared to PLGA alone. The addition of Sr did not show any differences between donors. Conclusion. This study details suitability of 3D printed polymer scaffolds for use in bone tissue applications. Both composite and pure polymer scaffolds promote osteogenesis in vitro. The introduction of ceramic filler and ion doping does not beneficially effect osteogenic potential and can reduce its ability compared to pure polymer. This study suggests the behaviour of control and osteoporotic cells are different and that osteoporotic cells are more prone to bone resorption. Therefore, it is important to design bone scaffolds that are specific to the patient as well as to the region of fracture


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_18 | Pages 109 - 109
14 Nov 2024
Weiden GVD Egmond NV Karperien M Both S Mastbergen S Emans P Caron J Custers R
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Introduction. The ACTIVE(Advanced Cartilage Treatment with Injectable-hydrogel Validation of the Effect) study investigates safety and performance of a novel dextran-tyramine hydrogel implant for treatment of small cartilage defects in the knee (0.5-2.0cm2). The hydrogel is composed of a mixture of natural polymer conjugates that are mixed intra-operatively and which cross-link in situ through a mild enzymatic reaction, providing a cell-free scaffold for cartilage repair. Method. The ACTIVE study is split into a safety (n=10) and a performance cohort (n=36). The Knee Injury and Osteoarthritis Outcome Score (KOOS), pain (numeric rating scale, NRS), Short-Form Health Survey (SF-36) were compared at baseline and 3, 6, and 12 months after surgery. The primary performance hypothesis is an average change in the KOOS from baseline to 12 months (ΔKOOS) greater than a minimal clinically important change (MIC) of 10. No statistical tests were performed as these are preliminary data on a smaller portion of the total study. Result. All patients of the safety cohort (n=10, mean age±SD, 30±9 years) were treated with the hydrogel for a symptomatic (NRS≥4) cartilage defect on the femoral condyle or trochlear groove (mean size±SD, 1.2±0.4cm2). No signs of an adverse foreign tissue reaction or serious adverse events were recorded within the safety cohort. At final follow-up mean KOOS±SD was 66.9±23.5, mean NRS resting±SD was 1.3±1.9, NRS activity±SD was 3.8±2.9 and mean SF-36±SD was 72.0±10.9. ΔKOOS was 21. One patient sustained new knee trauma prior to final follow-up, affecting final scores considerably. When excluded, ΔKOOS was 24(n=9). Conclusion. These promising initial findings provide a solid basis for continuation and expansion of this unique cartilage treatment. The MIC of 10 was surpassed. Though, results should be interpreted cautiously as they are based solely on preliminary data of the first 10 patients. Acknowledgements. Study is sponsored by Hy2Care, producer of the CartRevive®(dextran-tyramine) Hydrogel implant


Aims

The efficacy of saline irrigation for treatment of implant-associated infections is limited in the presence of porous metallic implants. This study evaluated the therapeutic efficacy of antibiotic doped bioceramic (vancomycin/tobramycin-doped polyvinyl alcohol composite (PVA-VAN/TOB-P)) after saline wash in a mouse infection model implanted with titanium cylinders.

Methods

Air pouches created in female BalBc mice by subcutaneous injection of air. In the first of two independent studies, pouches were implanted with titanium cylinders (400, 700, and 100 µm pore sizes) and inoculated with Staphylococcus aureus (1 × 103 or 1 × 106 colony-forming units (CFU)/pouch) to establish infection and biofilm formation. Mice were killed after one week for microbiological analysis. In the second study, pouches were implanted with 400 µm titanium cylinders and inoculated with S. aureus (1 × 103 or 1 × 106 CFU/pouch). Four groups were tested: 1) no bacteria; 2) bacteria without saline wash; 3) saline wash only; and 4) saline wash plus PVA-VAN/TOB-P. After seven days, the pouches were opened and washed with saline alone, or had an additional injection of PVA-VAN/TOB-P. Mice were killed 14 days after pouch wash.


Bone & Joint Research
Vol. 13, Issue 10 | Pages 596 - 610
21 Oct 2024
Toegel S Martelanz L Alphonsus J Hirtler L Gruebl-Barabas R Cezanne M Rothbauer M Heuberer P Windhager R Pauzenberger L

Aims

This study aimed to define the histopathology of degenerated humeral head cartilage and synovial inflammation of the glenohumeral joint in patients with omarthrosis (OmA) and cuff tear arthropathy (CTA). Additionally, the potential of immunohistochemical tissue biomarkers in reflecting the degeneration status of humeral head cartilage was evaluated.

Methods

Specimens of the humeral head and synovial tissue from 12 patients with OmA, seven patients with CTA, and four body donors were processed histologically for examination using different histopathological scores. Osteochondral sections were immunohistochemically stained for collagen type I, collagen type II, collagen neoepitope C1,2C, collagen type X, and osteocalcin, prior to semiquantitative analysis. Matrix metalloproteinase (MMP)-1, MMP-3, and MMP-13 levels were analyzed in synovial fluid using enzyme-linked immunosorbent assay (ELISA).


Bone & Joint Research
Vol. 13, Issue 9 | Pages 462 - 473
6 Sep 2024
Murayama M Chow SK Lee ML Young B Ergul YS Shinohara I Susuki Y Toya M Gao Q Goodman SB

Bone regeneration and repair are crucial to ambulation and quality of life. Factors such as poor general health, serious medical comorbidities, chronic inflammation, and ageing can lead to delayed healing and nonunion of fractures, and persistent bone defects. Bioengineering strategies to heal bone often involve grafting of autologous bone marrow aspirate concentrate (BMAC) or mesenchymal stem cells (MSCs) with biocompatible scaffolds. While BMAC shows promise, variability in its efficacy exists due to discrepancies in MSC concentration and robustness, and immune cell composition. Understanding the mechanisms by which macrophages and lymphocytes – the main cellular components in BMAC – interact with MSCs could suggest novel strategies to enhance bone healing. Macrophages are polarized into pro-inflammatory (M1) or anti-inflammatory (M2) phenotypes, and influence cell metabolism and tissue regeneration via the secretion of cytokines and other factors. T cells, especially helper T1 (Th1) and Th17, promote inflammation and osteoclastogenesis, whereas Th2 and regulatory T (Treg) cells have anti-inflammatory pro-reconstructive effects, thereby supporting osteogenesis. Crosstalk among macrophages, T cells, and MSCs affects the bone microenvironment and regulates the local immune response. Manipulating the proportion and interactions of these cells presents an opportunity to alter the local regenerative capacity of bone, which potentially could enhance clinical outcomes. Cite this article: Bone Joint Res 2024;13(9):462–473


The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 978 - 985
1 Sep 2024
Savoie III FH Delvadia BP Tate JP Winter JE Williams GH Sherman WF O’Brien MJ

Rotator cuff tears are common in middle-aged and elderly patients. Despite advances in the surgical repair of rotator cuff tears, the rates of recurrent tear remain high. This may be due to the complexity of the tendons of the rotator cuff, which contributes to an inherently hostile healing environment. During the past 20 years, there has been an increased interest in the use of biologics to complement the healing environment in the shoulder, in order to improve rotator cuff healing and reduce the rate of recurrent tears. The aim of this review is to provide a summary of the current evidence for the use of forms of biological augmentation when repairing rotator cuff tears.

Cite this article: Bone Joint J 2024;106-B(9):978–985.


The Bone & Joint Journal
Vol. 106-B, Issue 9 | Pages 1021 - 1030
1 Sep 2024
Oto J Herranz R Fuertes M Plana E Verger P Baixauli F Amaya JV Medina P

Aims

Bacterial infection activates neutrophils to release neutrophil extracellular traps (NETs) in bacterial biofilms of periprosthetic joint infections (PJIs). The aim of this study was to evaluate the increase in NET activation and release (NETosis) and haemostasis markers in the plasma of patients with PJI, to evaluate whether such plasma induces the activation of neutrophils, to ascertain whether increased NETosis is also mediated by reduced DNaseI activity, to explore novel therapeutic interventions for NETosis in PJI in vitro, and to evaluate the potential diagnostic use of these markers.

Methods

We prospectively recruited 107 patients in the preoperative period of prosthetic surgery, 71 with a suspicion of PJI and 36 who underwent arthroplasty for non-septic indications as controls, and obtained citrated plasma. PJI was confirmed in 50 patients. We measured NET markers, inflammation markers, DNaseI activity, haemostatic markers, and the thrombin generation test (TGT). We analyzed the ability of plasma from confirmed PJI and controls to induce NETosis and to degrade in vitro-generated NETs, and explored the therapeutic restoration of the impairment to degrade NETs of PJI plasma with recombinant human DNaseI. Finally, we assessed the contribution of these markers to the diagnosis of PJI.


Bone & Joint Research
Vol. 13, Issue 6 | Pages 261 - 271
1 Jun 2024
Udomsinprasert W Mookkhan N Tabtimnark T Aramruang T Ungsudechachai T Saengsiwaritt W Jittikoon J Chaikledkaew U Honsawek S

Aims

This study aimed to determine the expression and clinical significance of a cartilage protein, cartilage oligomeric matrix protein (COMP), in knee osteoarthritis (OA) patients.

Methods

A total of 270 knee OA patients and 93 healthy controls were recruited. COMP messenger RNA (mRNA) and protein levels in serum, synovial fluid, synovial tissue, and fibroblast-like synoviocytes (FLSs) of knee OA patients were determined using enzyme-linked immunosorbent assay, real-time polymerase chain reaction, and immunohistochemistry.


Orthopaedic Proceedings
Vol. 106-B, Issue SUPP_7 | Pages 1 - 1
8 May 2024
Wiewiorski M Barg A Valderrabano V
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Introduction. Autologous Matrix Induced Chondrogenesis (AMIC) for surgical treatment of osteochondral lesions of the talus (OCLT) has shown excellent clinical and radiological results at short term follow up two years after surgery. However, no mid-term follow up data is available. Aim. 1. To evaluate the clinical outcome after AMIC-aided reconstruction of osteochondral lesions of the talus at a minimum follow up time of five years. 2. To evaluate the morphology and quality of the regenerated cartilage by magnetic resonance imaging (MRI) at on at a minimum follow up time of five years. Methods. Seventeen patients prospectively underwent surgery receiving a AMIC-aided repair of OCLT consisting of debridement, autologous grafting, and sealing of the defect with a collagen scaffold (Chondro-Gide, Geistlich Surgery, Wolhusen, Switzerland). Clinical and radiological assessment was performed before and after a minimum of 60 months after surgery (average 78 months, range, 60–120). Clinical examination included the American Orthopaedic Foot & Ankle Society (AOFAS) ankle score and the Visual Analogue Scale (VAS). Radiological imaging consisted of MRI. The Magnetic Resonance Observation of Cartilage Repair Tissue (MOCART) score was applied. Results. The AOFAS ankle score improved significantly from a mean of 60 points preoperatively (range, 17–79) to 91 points (range, 70–100) postoperatively (p< 0.01). The preoperative pain score averaged a VAS of 5 (range, 2–8), improving to an average of 1.1 (range 0–8) (p< 0.01). The MOCART score for cartilage repair tissue on postoperative MRI averaged 71 points (range, 50–90). Conclusion. The AMIC-procedure is safe for the treatment of OCLT with overall good clinical and magnetic resonance imaging results at five years follow up


Bone & Joint Research
Vol. 13, Issue 5 | Pages 214 - 225
3 May 2024
Groven RVM Kuik C Greven J Mert Ü Bouwman FG Poeze M Blokhuis TJ Huber-Lang M Hildebrand F Cillero-Pastor B van Griensven M

Aims

The aim of this study was to determine the fracture haematoma (fxH) proteome after multiple trauma using label-free proteomics, comparing two different fracture treatment strategies.

Methods

A porcine multiple trauma model was used in which two fracture treatment strategies were compared: early total care (ETC) and damage control orthopaedics (DCO). fxH was harvested and analyzed using liquid chromatography-tandem mass spectrometry. Per group, discriminating proteins were identified and protein interaction analyses were performed to further elucidate key biomolecular pathways in the early fracture healing phase.


Different techniques have been described to address massive bone loss of the acetabulum in revision hip surgery. aMace has gained popularity as it provides customization aiming to restore hip centre and provide good initial stability in cases of large non-contained defects. It takes into account quality of host bone. Its porous defect filling scaffold provides an excellent surface for osteointegration. Our aim was to assess the short and mid-term outcomes of patients who underwent revision surgery using aMace system. Ethical approval was obtained. A retrospective study included all patients who had aMace between June 2013 and October 2022 allowing for a minimum of 12-months follow-up. Patients’ demographics, indication, bone-loss severity, reconstruction details, re-operation, complications, mortality, pain and function were assessed. 52 cases were performed by 13 surgeons with median 51 months follow-up. Median age was 72.7 years. 86.5% were female. Average BMI was 25.3. Average ASA grade was 3. 65% were classified as Paprosky IIIB and 32% were IIIA. 73% were found to have poor bone quality on CT. Main indication for aMace was massive bone loss/discontinuity secondary to aseptic loosening in 88.5%. 77% underwent single-stage revision. 53.8% had 2 or more previous revisions. 71% underwent stem revision in the same setting. 77% received a dual mobility bearing. Re-operation rate was 5.7% for instability and femoral PPF. LLD was reported in 9.6%. Permanent Sciatic nerve palsy occurred in 3.8% of the cases. 30-days mortality was 1.9%. Statistically significant post-op improvements in pain and mobility were reported (p<0.001). None of the acetabular components have been revised. Our study shows satisfactory surgical outcomes with a relatively low complication rate and significant pain and mobility improvements in the early to mid-term stages. We recommend these costly cases to be done in highly specialist centres adopting MDT approach