Objectives. All-suture anchors are increasingly used in rotator cuff repair procedures. Potential benefits include decreased bone damage. However, there is limited published evidence for the relative strength of fixation for all-suture anchors compared with traditional anchors. Materials and Methods. A total of four commercially available all-suture anchors, the ‘Y-Knot’ (ConMed), Q-FIX (Smith & Nephew), ICONIX (Stryker) and JuggerKnot (Zimmer Biomet) and a traditional anchor control TWINFIX Ultra PK Suture Anchor (Smith & Nephew) were tested in cadaveric human humeral head rotator cuff repair models (n = 24). This construct underwent cyclic loading applied by a mechanical testing rig (Zwick/Roell). Ultimate load to failure, gap formation at 50, 100, 150 and 200 cycles, and failure mechanism were recorded. Significance was set at p < 0.05. Results. Overall, mean maximum tensile strength values were significantly higher for the traditional anchor (181.0 N, standard error (. se). 17.6) compared with the all-suture anchors (mean 133.1 N . se. 16.7) (p = 0.04). The JuggerKnot anchor had greatest displacement at 50, 100 and 150 cycles, and at failure, reaching statistical significance over the control at 100 and 150 cycles (22.6 mm . se. 2.5 versus 12.5 mm . se. 0.3; and 29.6 mm . se. 4.8 versus 17.0 mm . se. 0.7). Every all-suture anchor tested showed substantial (> 5 mm) displacement between 50 and 100 cycles (6.2 to 14.3). All-suture anchors predominantly failed due to anchor pull-out (95% versus 25% of traditional anchors), whereas a higher proportion of traditional anchors failed secondary to suture breakage. Conclusion. We demonstrate decreased failure load, increased total displacement, and variable failure mechanisms in all-suture anchors, compared with traditional anchors designed for rotator cuff repair. These findings will aid the surgeon’s choice of implant, in the context of the clinical scenario. Cite this article: N. S. Nagra, N. Zargar, R. D. J. Smith, A. J. Carr. Mechanical properties of all-suture anchors for rotator cuff repair. Bone Joint Res 2017;6:82–89. DOI: 10.1302/2046-3758.62.BJR-2016-0225.R1

HXLPE acetabular liners were introduced to reduce wear-related complications in THA. However, post-irradiation thermal free radical stabilization can compromise mechanical properties, leave oxidation-prone residual free radicals, or both. Reports of mechanical failure of HXLPE acetabular liner rims raise concerns about thermal free radical stabilization and in vivo oxidization on implant properties. The purpose of this study is to explore the differences in the mechanical, physical and chemical properties of HXLPE acetabular liner rims after extended time in vivo between liners manufactured with different thermal free radical stabilization techniques. Remelted, single annealed and sequentially annealed retrieved HXLPE acetabular liners with in vivo times greater than 4.5 years were obtained from our implant retrieval laboratory. All retrieved liners underwent an identical sanitation and storage protocol. For mechanical testing, a total of 55 explants and 13 control liners were tested. Explant in vivo time ranged from 4.6 – 14 years and ex vivo time ranged from 0 – 11.6 years. Rim mechanical properties were tested by microindentation hardness testing using a Micromet II Vickers microhardness tester following ASTM standards. A subset of 16 explants with ex vivo time under one year along with five control liners were assessed for oxidation by FTIR, crystallinity by Raman spectroscopy, and evidence of microcracking by SEM. No significant difference in in vivo or ex vivo was found between thermal stabilization groups in either set of explants studied. In the mechanically tested explants, there was no significant correlation between in vivo time and Vickers hardness in any thermal stabilization group. A significant correlation was found between ex vivo time and hardness in remelted liners (r=.520, p = .011), but not in either annealed cohort. ANCOVA with ex vivo time as a covariate found a significant difference in hardness between the thermal free radical stabilization groups (p 0.1) was found in retrieved remelted (25%), single annealed (100%) and sequentially annealed (75%) liner rims. Crystallinity was increased in the subsurface region relative to control liners for both annealed, but not remelted, liner rims. Hardness was increased in oxidized rims for both annealed cohorts but not in the remelted cohort. Microcracking was only found along the surface of one unoxidized remelted liner rim. Mechanical properties were reduced at baseline and worsened after in vivo time for remelted HXLPE liner rims. Rim oxidation was detected in all groups. Oxidation was associated with increased crystallinity and hardness in annealed cohorts, but not remelted liners. Increased crystallinity and oxidation do not appear to be directly causing the worsened mechanical behavior of remelted HXLPE liner rims after extended in vivo time

Introduction. HXLPE acetabular liners were introduced to reduce wear-related complications in THA. However, post-irradiation thermal free radical stabilization can compromise mechanical properties, leave oxidation-prone residual free radicals, or both. Reports of mechanical failure of HXLPE acetabular liner rims raise concerns about thermal free radical stabilization and in vivo oxidization on implant properties. The purpose of this study is to explore the differences in the mechanical, physical and chemical properties of HXLPE acetabular liner rims after extended time in vivo between liners manufactured with different thermal free radical stabilization techniques. Material and methods. Remelted, single annealed and sequentially annealed retrieved HXLPE acetabular liners with in vivo times greater than 4.5 years were obtained from our implant retrieval laboratory. All retrieved liners underwent an identical sanitation and storage protocol. For mechanical testing, a total of 55 explants and 13 control liners were tested. Explant in vivo time ranged from 4.6 – 14.0 years and ex vivo time ranged from 0 – 11.6 years. Rim mechanical properties were tested by microindentation hardness testing using a Micromet II Vickers microhardness tester following ASTM standards. A subset of 16 explants with ex vivo time under one year along with five control liners were assessed for oxidation by FTIR, crystallinity by Raman spectroscopy, and evidence of microcracking by SEM. Results. No significant difference in in vivo or ex vivo was found between thermal stabilization groups in either set of explants studied. In the mechanically tested explants, there was no significant correlation between in vivo time and Vickers hardness in any thermal stabilization group. A significant correlation was found between ex vivo time and hardness in remelted liners (Δ=.520, p=.011), but not in either annealed cohort. ANCOVA with ex vivo time as a covariate found a significant difference in hardness between the thermal free radical stabilization groups (p<.0005, η. 2. = 0.322). Post hoc analysis revealed hardness was significantly lower in the retrieved remelted group compared to both the single annealed (p=.001) and sequentially annealed (p<.0005) cohorts. Hardness was significantly higher in the retrieved remelted liners compared to controls (p=.007), with no different in either annealed cohort (figure 1). Detectable subsurface oxidation (OI > 0.1) was found in retrieved remelted (25%), single annealed (100%) and sequentially annealed (75%) liner rims (figure 2). Crystallinity was increased in the subsurface region relative to control liners for both annealed, but not remelted, liner rims. Hardness was increased in oxidized rims for both annealed cohorts but not in the remelted cohort. Microcracking was only found along the surface of one unoxidized remelted liner rim. Conclusion. Mechanical properties were reduced at baseline and worsened after in vivo time for remelted HXLPE liner rims. Rim oxidation was detected in all groups. Oxidation was associated with increased crystallinity and hardness in annealed cohorts, but not remelted liners. Increased crystallinity and oxidation do not appear to be directly causing the worsened mechanical behavior of remelted HXLPE liner rims after extended in vivo time. For any tables or figures, please contact the authors directly

Introduction. HXLPE acetabular liners were introduced to reduce wear-related complications in THA. However, post-irradiation thermal free radical stabilization can compromise mechanical properties, leave oxidation-prone residual free radicals, or both. Reports of mechanical failure of HXLPE acetabular liner rims raise concerns about thermal free radical stabilization and in vivo oxidization on implant properties. The purpose of this study is to explore the differences in the mechanical, physical and chemical properties of HXLPE acetabular liner rims after extended time in vivo between liners manufactured with different thermal free radical stabilization techniques. Material and Methods. Remelted, single annealed and sequentially annealed retrieved HXLPE acetabular liners with in vivo times greater than 4.5 years were obtained from our implant retrieval laboratory. All retrieved liners underwent an identical sanitation and storage protocol. For mechanical testing, a total of 55 explants and 13 control liners were tested. Explant in vivo time ranged from 4.6 – 14.0 years and ex vivo time ranged from 0 – 11.6 years. Rim mechanical properties were tested by microindentation hardness testing using a Micromet II Vickers microhardness tester following ASTM standards. A subset of 16 explants with ex vivo time under one year along with five control liners were assessed for oxidation by FTIR, crystallinity by Raman spectroscopy, and evidence of microcracking by SEM. Results. No significant difference in in vivo or ex vivo time was found between thermal stabilization groups in either set of explants studied. In the mechanically tested explants, there was no significant correlation between in vivo time and Vickers hardness in any thermal stabilization group. A significant correlation was found between ex vivo time and hardness in remelted liners (r=.520, p=.011), but not in either annealed cohort. ANCOVA with ex vivo time as a covariate found a significant difference in hardness between the thermal free radical stabilization groups (p<.0005, η. 2. = 0.322). Post hoc analysis revealed hardness was significantly lower in the retrieved remelted group compared to both the single annealed (p=.001) and sequentially annealed (p<.0005) cohorts. Hardness was significantly higher in the retrieved remelted liners compared to controls (p=.007), with no different in either annealed cohort. Detectable subsurface oxidation (OI > 0.1) was found in retrieved remelted (25%), single annealed (100%) and sequentially annealed (75%) liner rims. Crystallinity was increased in the subsurface region relative to control liners for both annealed, but not remelted, liner rims. Hardness was increased in oxidized rims for both annealed cohorts but not in the remelted cohort. Microcracking was only found along the surface of one unoxidized remelted liner rim. Conclusion. Mechanical properties were reduced at baseline and worsened after in vivo time for remelted HXLPE liner rims. Rim oxidation was detected in all groups. Oxidation was associated with increased crystallinity and hardness in annealed cohorts, but not remelted liners. Increased crystallinity and oxidation do not appear to be directly causing the worsened mechanical behavior of remelted HXLPE liner rims after extended in vivo time. For any figures or tables, please contact authors directly

Aims. The aim of this study was to investigate the global and local impact of fat on bone in obesity by using the diet-induced obese (DIO) mouse model. Methods. In this study, we generated a diet-induced mouse model of obesity to conduct lipidomic and 3D imaging assessments of bone marrow fat, and evaluated the correlated bone adaptation indices and bone mechanical properties. Results. Our results indicated that bone mass was reduced and bone mechanical properties were impaired in DIO mice. Lipidomic sequencing and bioinformatic analysis identified 373 differential lipids, 176 of which were upregulated and 197 downregulated. Functional enrichment analysis revealed a significant downregulation of the pathways: fat digestion and absorption (ko04975) and lipolysis regulation in adipocytes (ko04923) in DIO mice, leading to local fat accumulation. The use of 3D imaging confirmed the increase in fat accumulation within the bone marrow cavity of obese mice. Conclusion. Our study sheds light on the intricate interplay between fat and bone, and provides a non-toxic and non-invasive method for measuring marrow adipose tissue. Cite this article: Bone Joint Res 2023;12(9):580–589

Aims. Gap junction intercellular communication (GJIC) in osteocytes is impaired by oxidative stress, which is associated with age-related bone loss. Ageing is accompanied by the accumulation of advanced oxidation protein products (AOPPs). However, it is still unknown whether AOPP accumulation is involved in the impairment of osteocytes’ GJIC. This study aims to investigate the effect of AOPP accumulation on osteocytes’ GJIC in aged male mice and its mechanism. Methods. Changes in AOPP levels, expression of connexin43 (Cx43), osteocyte network, and bone mass were detected in 18-month-old and three-month-old male mice. Cx43 expression, GJIC function, mitochondria membrane potential, reactive oxygen species (ROS) levels, and nicotinamide adenine dinucleotide phosphate (NADPH) oxidase activation were detected in murine osteocyte-like cells (MLOY4 cells) treated with AOPPs. The Cx43 expression, osteocyte network, bone mass, and mechanical properties were detected in three-month-old mice treated with AOPPs for 12 weeks. Results. The AOPP levels were increased in aged mice and correlated with degeneration of osteocyte network, loss of bone mass, and decreased Cx43 expression. AOPP intervention induced NADPH oxidase activation and mitochondrial dysfunction, triggered ROS generation, reduced Cx43 expression, and ultimately impaired osteocytes’ GJIC, which were ameliorated by NADPH oxidase inhibitor apocynin, mitochondria-targeted superoxide dismutase mimetic (mito-TEMPO), and ROS scavenger N-acetyl cysteine. Chronic AOPP loading accelerated the degradation of osteocyte networks and decreased Cx43 expression, resulting in deterioration of bone mass and mechanical properties in vivo. Conclusion. Our study suggests that AOPP accumulation contributes to age-related impairment of GJIC in osteocytes of male mice, which may be part of the pathogenic mechanism responsible for bone loss during ageing. Cite this article: Bone Joint Res 2022;11(7):413–425

Type-2 Diabetic (T2D) patients experience up to a 3-fold increase in bone fracture risk[1]. Paradoxically, T2D-patients have a normal or increased bone mineral density when compared to non-diabetic patients. This implies that T2D has a deleterious effect on bone quality, whereby the intrinsic material properties of the bone matrix are altered. Creating clinical challenges as current diagnostic techniques are unable to accurately predict the fracture probability in T2D-patients. To date, the relationship between cyclic fatigue loading, mechanical properties and microdamage accumulation of T2D-bone tissue has not yet been examined and thus our objective is to investigate this relationship. Ethically approved femoral heads were obtained from patients, with (n=8) and without (n=8) T2D. To obtain the mechanical properties of the sample, one core underwent a monotonic compression test to 10% strain, the other core underwent a cyclic compression test at a normalized stress ratio between 0.0035mm/mm and 0.016mm/mm to a maximum strain of 3%. Microdamage was evaluated by staining the tissue with barium sulfate precipitate [2] and conducting microcomputed tomography scanning with a voxel size of 10μm. The monotonically tested T2D-group showed no statistical difference in mechanical properties to the non-T2D-group, even when normalised against BV/TV. There was also no difference in BV/TV. For the cyclic test, the T2D-group had a significantly higher initial modulus (p<0.01) and final modulus (p<0.05). There was no difference in microdamage accumulation. Previous population-level studies have found that T2D-patients have been shown to have an increased fracture risk when compared to non-T2D-patients. This research indicates that T2D does not impair the mechanical properties of trabecular bone from the femoral heads of T2D-patients, suggesting that other mechanisms may be responsible for the increased fracture risk seen in T2D-patients

The anterior cruciate ligament (ACL) is the connective tissue located at the end of long bones providing stability to the knee joint. After tear or rupture clinical reconstruction of the tissue remains a challenge due to the particular mechanical properties required for proper functioning of the tissue. The outstanding mechanical properties of the ACL are characterized by a viscoelastic behavior responsible of the dissipation of the loads that are transmitted to the bone. These mechanical properties are the result of a very specialized graded extracellular matrix that transitions smoothly between the heterotypic cells, stiffness and composition of the ACL and the adjacent bone. Thus, mimicking the zonal biochemical composition, cellular phenotype and organization are key to reset the proper functioning of the ACL. We have previously shown how the biochemical composition presented to cells in electrospun scaffolds results in haptokinesis, reverting contact-guidance effects. [1]. Here, we demonstrate that contact guidance can also be disrupted by structural parameters in aligned wavy scaffolds. The presentation of a wavy fiber arrangement affected the cell organization and the deposition of a specific ECM characteristic of fibrocartilage. Cells cultured in wavy scaffolds grew in aggregates, deposited an abundant ECM rich in fibronectin and collagen II, and expressed higher amounts of collagen II, X and tenomodulin as compared to aligned scaffolds. In-vivo implantation in rabbits of triphasic scaffolds accounting for aligned-wavy-aligned zones showed a high cellular infiltration and the formation of an oriented ECM, as compared to traditional aligned scaffolds. [2]

The purpose of the study was to compare the mechanical properties, oxidation and wear resistance of a vitamin E blended and moderately crosslinked polyethylene for total knee arthroplasty (MXE) in comparison with clinically established polyethylene materials. The following polyethylene materials were tested: CPE (30 kGy e-beam sterilized), XLPE (75 kGy gamma crosslinked @ 100°C), ViXLPE (0.1 % vitamin E blended, 80 kGy e-beam crosslinked @ 100°C), and MXE (0.1 % vitamin E blended polyethylene, 30 kGy gamma sterilized). For the different tests, the polyethylene materials were either unaged or artificially aged for two or six weeks according to ASTM F2003-02. The oxidation index was measured based on ASTM F2102 at a 1 mm depth. Small punch testing was performed based on ASTM F2977. Mechanical properties were measured on unaged materials according to ASTM D638. Wear simulation was performed on a load controlled 3 + 1 station knee wear simulator (EndoLab GmbH, Thansau, Germany) capable of reproducing loads and movement of highly demanding activities (HDA) as well as ISO 14243-1 load profiles. The load profiles were applied for 5 million cycles (mc) or delamination of the polyethylene components. Medium size AS e.motion. ®. PS Pro (Aesculap AG, Tuttlingen, Germany) femoral and tibial components with a ZrN-multilayer surface, as well as Columbus. ®. CR cobalt-chrome alloy femoral and tibial components were tested. Particle analysis was performed on the serum samples of the ISO 14243-1 wear simulations based on ISO 17853:2011 and ASTM F1877. The analysis of the mechanical properties show that moderately crosslinked polyethylene (MXE) might be a superior material for total knee arthroplasty applications [Schwiesau et al. 2021]. The addition of vitamin E in a moderately crosslinked polyethylene prevented its oxidation, kept its mechanical characteristics, and maintained a low wear, even under a HDA knee wear simulation

Currently, fibrin glue obtained from fibrinogen and thrombin of human and animal blood are widely investigated to use as injectable hydrogel for tissue engineering which contributes to minimally invasive surgery, superior biodegradability, cell attachment, proliferation and regenerating new tissue. However, most of them fail to achieve to be used for tissue engineering application because of a risk of immune response and poor mechanical properties. To overcome the limitation of fibrin glue and to reduce the usage of products from human and animal blood, the artificial fibrin glue materials were developed. Recently, cellulose nanofiber (CNF) as reinforcing agent has been explored for many tissue engineering applications such as bone and cartilage due to its impressive biological compatibility, biodegradability and mechanical properties. CNF was extracted from cassava pulp. PEO-PPO-PEO diacrylate block copolymer is a biodegradable synthetic polymers which is water insoluble hydrogel after curing by UV light at low intensity. To enhance the cell adhesion abilities, gelatin methacrylate (GelMA), the denature form of collagen was used to incorporate into hydrogel. The aim of this study was to develop the artificial fibrin glue from CNF reinforced PEO-PPO-PEO diacrylate block copolymer/GelMA injectable hydrogel. CNF/PEO-PPO-PEO diacrylate block copolymer/GelMA injectable hydrogels were prepared with 2-hydroxy-1-(4-(hydroxy ethoxy) phenyl)-2-methyl-1-propanone (Irgacure 2959) as a photoinitiator. The physicochemical properties were investigated by measuring various properties such as thickness, gel fraction, mechanical properties and water uptake. At optimal preparation condition, CNF reinforced injectable hydrogel was successful prepared after curing with UV light within 7 minutes. This hydrogel showed gel fraction and water uptake of 81 and 85%, respectively. The cytotoxicity, cell adhesion and proliferation of CNF reinforced injectable hydrogel was presented. Cellulose nanofiber from casava pulp was successfully used to prepare injectable hydrogel as artificial fibrin glue for tissue engineering. The hydrogel showed good physical properties which can be applied to use for tissue engineering application

Jellyfish collagens exhibit auspicious perspectives for tissue engineering applications primarily due to their outstanding compatibility with a wide range of cell types, low immunogenicity and biodegradability. Furthermore, derived from a non-mammalian source, jellyfish collagens reduce the risk of disease transmission, minimising therefore the ethical and safety concerns. The current study aims to investigate the potential of 3-dimensional jellyfish collagen sponges (3D-JCS) in promoting bone tissue regeneration. Both qualitative and quantitative analyses were performed in order to assess adhesion and proliferation of MC3T3 cells on 3D-JCL, as well as cell migration and bone-like ECM production. Histological and fluorescent dyes were used to stain mineral deposits (i.e. Alizarin Red S (ARS), Von Kossa, Tetracycline hydrochloride) while images were acquired using optical and confocal microscopy. Qualitative data indicated successful adhesion and proliferation of MC3T3 cells on the 3D-JCS as well as cell migration along with ECM production both on the inner and outer surface of the scaffolds. Moreover, quantitative analyses indicated a four-fold increase of ARS uptake between 2- and 3-dimensional cultures (N=3) as well as an eighteen-fold increase of ARS uptake for the 3D-JCS (N=3) when cultured in osteogenic conditions compared to control. This suggests the augmented osteogenic potential of MC3T3 cells when cultured on 3D-JCS. Nevertheless, the cell-mediated mineral deposition appeared to alter the mechanical properties of the jellyfish collagen sponges that were previously reported to exhibit low mechanical properties (compressive modulus: 1-2 kPa before culture). The biocompatibility, high porosity and pore interconnectivity of jellyfish collagen sponges promoted adhesion and proliferation of MC3T3 cells as well as cell migration and bone-like ECM production. Their unique features recommend the jellyfish collagen sponges as superior biomaterial scaffolds for bone tissue regeneration. Further studies are required to quantify the change in mechanical properties of the cell-seeded scaffolds and confirm their suitability for bone tissue regeneration. We predict that the 3D-JCS will be useful for future studies in both bone and bone-tendon interface regeneration. Acknowledgments. This research has been supported by a Medical Research Scotland Studentship award (ref: -50177-2019) in collaboration with Jellagen Ltd

Production of porous titanium bone implants is a highly promising research and application area due to providing high osseointegration and achieving the desired mechanical properties. Production of controlled porosity in titanium implants is possible with laser powder bed fusion (L- PBF) technology. The main topics of this presentation includes the L-PBF process parameter optimization to manufacture thin walls of porous titanium structures with almost full density and good mechanical properties as well as good dimensional accuracy. Moreover, the cleaning and coating process of these structures to further increase osseointegration and then in-vitro biocompatibility will be covered

Introduction. According to American Joint Replacement Registry, particle mediated osteolysis represents 13 % of the knee revision surgeries performed in the United States. The comprehension of mechanical and wear properties of materials envisioned for TJR is a key step in product development. Furthermore, the maintenance of UHMWPE mechanical properties after material modification is an important aspect of material success. Initial studies conducted by our research group demonstrated that the incorporation of ibuprofen in UHMWPE had a minor impact on UHMWPE physicochemical and mechanical properties. Drug release was also evaluated and resulted in an interesting profile as a material to be used as an anti-inflammatory system. Therefore, the present study investigated the effect of drug release on the mechanical and biological properties of ibuprofen-loaded UHMWPE. Experimental. UHMWPE resin GUR 1020 from Ticona was for sample preparation. Samples with drug concentrations of 3% and 5% wt were consolidated as well as samples without anti-inflammatory addition through compression molding at 150 °C and 5 MPa for 15 minutes. Mechanical properties were evaluated via the tensile strength experiment (ASTM D638) and dynamic mechanic tests. Wear resistance was measured using the pin on disc (POD) apparatus. Finally, cytotoxicity analysis was conducted based on ISO 10993–5. Results. Dynamic-mechanic analysis demonstrated no difference in flexion modulus and stress for all materials (Table 1). No difference was also verified during cyclical loading experiments (Table 1), which indicates that the drug concentration added to material composition did not affect these properties. POD experiments were proposed to evaluate wear resistance of ibuprofen-loaded UHMWPE samples considering the combination of materials similar to those employed in TJR. Results from POD tests are presented in Table 1. Volumetric wear was close to zero for all samples after 200 thousand cycles. Comprehension of the effect of drug release on mechanical properties is essential to estimate how the material will behave after implantation. Therefore, mechanical properties were assessed after 30 days of ibuprofen release and the results were compared with those obtained in samples as prepared (Table 2). Initial results demonstrated a decrease in elastic modulus in samples prepared with ibuprofen. However, no difference was verified between UHMWPE, UHMWPE 3% IBU and UHMWPE 5% IBU after ibuprofen release. Finally, cell viability of UHMWPE 3% IBU and UHMWPE 5% was found to be superior to 100% (Figure 1). Therefore, both materials can be considered nontoxic. Conclusions. Ibuprofen-loaded UHMWPE did not demonstrate a significant influence on the mechanical and biological behavior of UHMWPE. Dynamic-mechanical tests demonstrated constancy for all samples under analysis. Wear testing resulted in gravimetric wear close to zero, for all tested materials. Mechanical properties conducted after 30 days of ibuprofen release also had a positive outcome. Although presenting a difference in modulus prior and after release tests, modulus and tensile yield stress remained inside acceptable range indicated to UHMWPE used in orthopedic implants. Furthermore, after drug elution UHMWPE 3% IBU and UHMWPE 5% IBU recovered original UHMWPE properties. Cytotoxicity assessment was performed and both ibuprofen-based formulations were considered nontoxic according to ISO 10993–5. For any figures or tables, please contact the authors directly

The aim of this study is to print 3D polycaprolactone (PCL) scaffolds at high and low temperature (HT/LT) combined with salt leaching to induced porosity/larger pore size and improve material degradation without compromising cellular activity of printed scaffolds. PCL solutions with sodium chloride (NaCl) particles either directly printed in LT or were casted, dried, and printed in HT followed by washing in deionized water (DI) to leach out the salt. Micro-Computed tomography (Micro-CT) and scanning electron microscope (SEM) were performed for morphological analysis. The effect of the porosity on the mechanical properties and degradation was evaluated by a tensile test and etching with NaOH, respectively. To evaluate cellular responses, human bone marrow-derived mesenchymal stem/stromal cells (hBMSCs) were cultured on the scaffolds and their viability, attachment, morphology, proliferation, and osteogenic differentiation were assessed. Micro-CT and SEM analysis showed that porosity induced by the salt leaching increased with increasing the salt content in HT, however no change was observed in LT. Structure thickness reduced with elevating NaCl content. Mass loss of scaffolds dramatically increased with elevated porosity in HT. Dog bone-shaped specimens with induced porosity exhibited higher ductility and toughness but less strength and stiffness under the tension in HT whereas they showed decrease in all mechanical properties in LT. All scaffolds showed excellent cytocompatibility. Cells were able to attach on the surface of the scaffolds and grow up to 14 days. Microscopy images of the seeded scaffolds showed substantial increase in the formation of extracellular matrix (ECM) network and elongation of the cells. The study demonstrated the ability of combining 3D printing and particulate leaching together to fabricate porous PCL scaffolds. The scaffolds were successfully printed with various salt content without negatively affecting cell responses. Printing porous thermoplastic polymer could be of great importance for temporary biocompatible implants in bone tissue engineering applications

This study aims to assess the fracture mechanics of type-2 diabetic (T2D) femoral bone using innovative site-specific tests, whilst also examining the cortical and trabecular bone microarchitecture from various regions using micro-computed tomography (CT) of the femur as the disease progresses. Male [Zucker Diabetic Fatty (ZDF: fa/fa) (T2D) and Zucker Lean (ZL: fa/+) (Control)] rats were euthanized at 12-weeks of age, thereafter, right and left femora were dissected (Right femora: n = 6, per age, per condition; Left femora: n=8-9, per age, per condition). Right femurs were notched in the posterior of the midshaft. Micro-CT was used to scan the proximal femur, notched and unnotched femoral midshaft (cortical) of the right femur and the distal metaphysis (trabecular) of the left femur to investigate microarchitecture and composition. Right femurs were fracture toughness tested to measure the stress intensity factor (Kic) followed by a sideways fall test using a custom-made rig to investigate femoral neck mechanical properties. There was no difference in trabecular and cortical tissue material density (TMD) between T2D and control rats. Cortical thickness was unchanged, but trabeculae were thinner (p<0.01) in T2D rats versus controls. However, T2D rats had a greater number of trabeculae (p<0.05) although trabecular spacing was not different to controls. T2D rats had a higher connectivity distribution (p<0.05) and degree of anisotropy (p<0.05) in comparison to controls. There was no difference in the mechanical properties between strains. At 12-weeks of age, rats are experiencing early-stage T2Ds and the disease impact is currently not very clear. Structural and material properties are unchanged between strains, but the trabecular morphology shows that T2D rats have more trabecular struts present in order to account for the thinner trabeculae

Reducing wear of endoprosthetic implants is still an important goal in order to increase the life time of the implant. Endoprosthesis failure can be caused by many different mechanisms, such as abrasive wear, corrosion, fretting or foreign body reactions due to wear accumulation. Especially, modular junctions exhibit high wear rates and corrosion due to micromotions at the connection of the individual components. The wear generation of cobalt-chromium-molybdenum alloys (CoCrMo) is strongly influenced by the microstructure. Therefore, the aim of this work is to investigate the subsurface phase transformation by deep rolling manufacturing processes in combination with a “sub-zero” cooling strategy. We analyzed the influence on the phase structure and the mechanical properties of wrought CoCr28Mo6 alloy (ISO 5832-12) by a deep rolling manufacturing process at various temperatures (+25°C,-10°C,-35°C) and different normal forces (700N and 1400N). Surface (S. a. ,S. z. ) and subsurface characteristics (residual stress) as well as biological behavior were investigated for a potential implant application. We showed that the microstructure of CoCr28Mo6 wrought alloy changes depending on applied force and temperature. The face centered cubic (fcc) phase could be transformed to a harder hexagonal-close-packed (hcp) phase structure in the subsurface. The surface could be smoothed (up to S. a. = 0.387 µm±0.185 µm) and hardened (≥ 700 HV 0.1) at the same time. The residual stress was increased by more than 600% (n=3). As a readout for metabolic activity of MonoMac (MM6) and osteosarcoma (SaOS-2) cells a WST assay (n=3) was used. The cells showed no significant negative effect of the sub-zero manufacturing process. We showed that deep rolling in combination with an innovative cooling strategy for the manufacturing process has a great potential to improve the mechanical properties of CoCr28Mo6 wrought alloy, by subsurface hardening and phase transformation for implant applications

Biomaterials with mechanical or biological competence are ubiquitous in musculoskeletal disorders, and understanding the inflammatory response they trigger is key to guide tissue regeneration. While macrophage role has been widely investigated, immune response is regulated by other immune cells, including neutrophils, the most abundant leukocyte in human blood. As first responders to injury, infection or material implantation, neutrophils recruit other immune cells, and therefore influence the onset and resolution of chronic inflammation, and macrophage polarization. This response depends on the physical and chemical properties of the biomaterials, among other factors. In this study we report an in vitro culture model to describe the most important neutrophil functions in relation to tissue repair. We identified neutrophil survival and death, neutrophils extracellular trap formation, release of reactive oxygen species and degranulation with cytokines release as key functions and introduced a corresponding array of assays. These tests were suitable to identify clear differences in the response by neutrophils that were cultured on material of different origin, stiffness and chemical composition. Overall, substrates from biopolymers of natural origin resulted in increased survival, less neutrophil extracellular trap formation, and more reactive oxygen species production than synthetic polymers. Within the range of mechanical properties explored (storage modulus below 5 k Pa), storage modulus of covalently crosslinked hyaluronic acid hydrogels did not significantly alter neutrophils response, whereas polyvinyl alcohol gels of matching mechanical properties displayed a response indicating increased activation. Additionally, we present the effect of material stiffness, charge, coating and culture conditions in the measured neutrophils response. Further studies are needed to correlate the neutrophil response to tissue healing. By deciphering how neutrophils initiate and modulate the immune response to material implantation, we aim at introducing new principles to design immunomodulatory biomaterials for musculoskeletal disorders. Acknowledgments. This work was supported by the AO Foundation, AO CMF, grant AOCMF-21-04S

Rotator cuff tears are common, with failure rates of up to 94% for large and massive tears. 1. For such tears, reattachment of the musculotendinous unit back to bone is problematic, and any possible tendon-bone repair heals through scar tissue rather than the specially adapted native enthesis. We aim to develop and characterise a novel soft-hard tissue connector device, specific to repairing/bridging the tendon-bone injury in significant rotator cuff tears, employing decellularised animal bone partially demineralised at one end for soft tissue continuation. Optimisation samples of 15×10×5mm. 3. , trialled as separate cancellous and cortical bone samples, were cut from porcine femoral condyles and shafts, respectively. Samples underwent 1-week progressive stepwise decellularisation and a partial demineralisation process of half wax embedding and acid bathing. Characterisations were performed histologically for the presence/absence of cellular staining in both peripheral and central tissue areas (n=3 for each cortical/cancellous, test/PBS control and peripheral/central group), and with BioDent reference point indentation (RPI) for pre- and post-processing mechanical properties. Histology revealed absent cellular staining in peripheral and central cancellous samples, whilst reduced in cortical samples compared to controls. Cancellous samples decreased in wet mass after decellularisation by 45.3% (p<0.001). RPI measurements associated with toughness (total indentation depth, indentation depth increase) and elasticity (1st cycle unloading slope) showed no consistent changes after decellularisation. X-rays confirmed half wax embedding provided predictable control of the mineralised-demineralised interface position. Initial optimisation trials show proof-of-concept of a soft-hard hybrid scaffold as an immune compatible xenograft for irreparable rotator cuff tears. Decellularisation did not appreciably affect mechanical properties, and further biological, structural and chemical characterisations are underway to assess validity before in vivo animal trials and potential clinical translation

In this work, we propose a new quantitative way of evaluating acute compartment syndrome (ACS) by dynamic mechanical assessment of soft tissue changes. First, we have developed an animal model of ACS to replicate the physiological changes during the condition. Secondly, we have developed a mechanical assessment tool for quantitative pre-clinical assessment of ACS. Our hand-held indentation device provides an accurate method for investigations into the local dynamic mechanical properties of soft tissue and for in-situ non-invasive assessment and monitoring of ACS. Our compartment syndrome model was developed on the cranial tibial and the peroneus tertius muscles of a pig's leg (postmortem). The compartment syndrome pressure values were obtained by injecting blood from the bone through the muscle. To enable ACS assessment by a hand-held indentation device we combined three main components: a load cell, a linear actuator and a 3-axis accelerometer. Dynamic tests were performed at a frequency of 0.5 Hz and by applying an amplitude of 0.5 mm. Another method used to observe the differences in the mechanical properties inside the leg was a 3D Digital Image Correlation (3D-DIC). Videos were taken from two different positions of the pig's leg at different pressure values: 0 mmHg, 15 mmHg and 40 mmHg. Two strains along the x axis (Exx) and y axis (Eyy) were measured. Between the two pressure cases (15 mmHg and 40 mmHg) a clear deformation of the model is visible. In fact, the bigger the pressure, the more visible the increase in strain is. In our animal model, local muscle pressures reached values higher than 40 mmHg, which correlate with observed human physiology in ACS. In our presentation we will share our dynamic indentation results on this model to demonstrate the sensitivity of our measurement techniques. Compartment syndrome is recognised as needing improved clinical management tools. Our approach provides both a model that reflects physiological behaviour of ACS, and a method for in-situ non-invasive assessment and monitoring

Even minor lesions in articular cartilage (AC) can cause underlying bone damage creating an osteochondral (OC) defect. OC defects can cause pain, impaired mobility and can develop to osteoarthritis (OA). OA is a disease that affects nearly 10% of the population worldwide. [1]. , and represents a significant economic burden to patients and society. [2]. While significant progress has been made in this field, realising an efficacious therapeutic option for unresolved OA remains elusive and is considered one of the greatest challenges in the field of orthopaedic regenerative medicine. [3]. Therefore, there is a societal need to develop new strategies for AC regeneration. In recent years there has been increased interest in the use of tissue-specific aligned porous freeze-dried extracellular matrix (ECM) scaffolds as an off-the-shelf approach for AC repair, as they allow for cell infiltration, provide biological cues to direct target-tissue repair and permit aligned tissue deposition, desired in AC repair. [4]. However, most ECM-scaffolds lack the appropriate mechanical properties to withstand the loads passing through the joint. [5]. One solution to this problem is to reinforce the ECM with a stiffer framework made of synthetic materials, such as polylactic acid (PLA). [6]. Such framework can be 3D printed to produce anatomically accurate implants. [7]. , attractive in personalized medicine. However, typical 3D prints are static, their design is not optimized for soft-hard interfaces (OC interface), and they may not adapt to the cyclic loading passing through our joints, thus risking implant failure. To tackle this limitation, more compliant or dynamic designs can be printed, such as coil-shaped structures. [8]. Thus, in this study we use finite element modelling to create different designs that mimic the mechanical properties of AC and prototype them in PLA, using polyvinyl alcohol as support. The optimal design will be combined with an ECM scaffold containing a tailored microarchitecture mimicking aspects of native AC. Acknowledgments: This project has received funding from the European Union's Horizon Europe research and innovation MSCA PF programme under grant agreement No. 101110000