Hemodynamic Implications of STABILISE Technique for Aortic Dissection Repair.

BACKGROUND: The stent-assisted balloon-induced intimal disruption and relamination (STABILISE) technique for treatment of type B dissection has shown promising clinical results at mid-term. Computational modeling is a way of noninvasively obtaining hemodynamic effects, such as pressure and wall shear stress, leading to a better understanding of potential benefits. Particular areas of interest are (1) the effect of intimal disruption and re-lamination and (2) the effect of the bare metal stent in the visceral aortic segment. METHODS: Single-center prospective case series. Data from 5 consecutive locally performed cases of STABILISE technique were analyzed. Included cases were type B aortic dissection with or without prior de-branching. The STABILISE procedure had to be performed without 30-day major complications. Preoperative and postoperative imaging data for each patient were transferred to the biomedical engineering team. Each case was reconstructed, meshed, and simulated with computational fluid dynamics using patient-specific data (heart rate, blood pressure, height, and weight). Hemodynamic parameters were then extracted from the simulations. RESULTS: In all cases, computational analysis showed for postoperative patients: (1) a drop in pressure difference between lumina and (2) lower wall shear stress effects, compared to their preoperative status. These observations were most pronounced in the visceral aortic segment. CONCLUSIONS: Computational modeling shows favourable changes in the flow dynamics of type B dissection treated using the STABILISE technique. This may suggest protective effects of this technique for long-term aortic healing and cicatrization.

Current transfusion practice and need for new blood products to ensure blood supply for patients with major hemorrhage in Europe.

BACKGROUND: New blood products are considered for treatment of patients with major hemorrhage. The aim of this report is to describe the current transfusion practices in Europe for patients with major hemorrhage and explore the need for new or modified blood products to ensure prehospital and in-hospital blood supply. STUDY DESIGN AND METHOD: The European Blood Alliance (EBA) Working Group on Innovation and New Blood Products' subgroup on major hemorrhage performed a survey among the EBA member states. RESULTS: The response rate was 58% (17 responses from 15 of the 26 EBA member states). Of these, sixteen (94%) provide massive transfusion packages (MTPs) with balanced ratio of red blood cells and plasma. Seven of the respondents included platelets from the start of treatment. Eleven (65%) provide prehospital blood products, mainly red cell concentrates or dried and/or thawed plasma with 5 days of extended storage. Two countries provide prehospital whole blood. Twelve respondents (71%) saw a need for implementation of new or modified blood components in their institution. The top three priorities were whole blood (12 of 12, 100%), dried plasma (8 of 12, 67%), and cold-stored platelets (7 of 12, 58%). DISCUSSION: Current national guidelines for use of blood products in patients with major hemorrhage in Europe agree on the use of balanced transfusion, however the timing and source of platelets differ. Blood products for prehospital transfusion are available in several European countries. An interest in new or modified blood products for patients with major hemorrhage was observed, especially for whole blood.

Proximal false lumen thrombosis is associated with low false lumen pressure and fewer complications in type B aortic dissection.

BACKGROUND: Improved risk stratification is a key priority for type B aortic dissection (TBAD). Partial false lumen thrombus morphology is an emerging predictor of complications. However, partial thrombosis is poorly defined, and its evaluation in clinical studies has been inconsistent. Thus, we aimed to characterize the hemodynamic pressure in TBAD and determine how the pressure relates to the false lumen thrombus morphology and clinical events. METHODS: The retrospective admission computed tomography angiograms of 69 patients with acute TBAD were used to construct three-dimensional computational models for simulation of cyclical blood flow and calculation of pressure. The patients were categorized by the false lumen thrombus morphology as minimal, extensive, proximal or distal thrombosis. Linear regression analysis was used to compare the luminal pressure difference between the true and false lumen for each morphology group. The effect of morphology classification on the incidence of acute complications within 14 days was studied using logistic regression adjusted for clinical parameters. A survival analysis for adverse aortic events at 1 year was also performed using Cox regression. RESULTS: Of the 69 patients, 44 had experienced acute complications and 45 had had an adverse aortic event at 1 year. The mean ± standard deviation age was 62.6 ± 12.6 years, and 75.4% were men. Compared with the patients with minimal thrombosis, those with proximal thrombosis had a reduced false lumen pressure by 10.1 mm Hg (95% confidence interval [CI], 4.3-15.9 mm Hg; P = .001). The patients who had not experienced an acute complication had had a reduced relative false lumen pressure (-6.35 mm Hg vs -0.62 mm Hg; P = .03). Proximal thrombosis was associated with fewer acute complications (odds ratio, 0.17; 95% CI, 0.04-0.60; P = .01) and 1-year adverse aortic events (hazard ratio, 0.36; 95% CI, 0.16-0.80; P = .01). CONCLUSIONS: We found that proximal false lumen thrombosis was a marker of reduced false lumen pressure. This might explain how proximal false lumen thrombosis appears to be protective of acute complications (eg, refractory hypertension or pain, aortic rupture, visceral or limb malperfusion, acute expansion) and adverse aortic events within the first year.

Survey of blood centre readiness regarding removal of DEHP from blood bag sets: The BEST Collaborative Study.

BACKGROUND AND OBJECTIVES: Di(2-ethylhexyl) phthalate (DEHP) must be removed from blood bag sets in Europe by 27 May 2025. DEHP is known to interact with the red blood cell (RBC) membrane, resulting in reduced haemolysis and thus prolonging shelf-life. Current non-DEHP alternatives result in increased haemolysis requiring reconsideration of the RBC shelf-life. Although the immediate impact of eliminating DEHP is to the European community, the non-DEHP movement could affect blood bag set availability globally. The purpose of this survey is to understand blood centre readiness regarding the transition to non-DEHP blood collection and storage systems. MATERIALS AND METHODS: A 24-question on-line survey was completed by members of the Biomedical Excellence for Safer Transfusion Collaborative research network. RESULTS: Responses were obtained from 16 blood collection or processing institutions. A majority of respondents (12/16) indicated that both shelf-life and haemolysis were equally important in selecting non-DEHP blood bag sets. Six respondents would accept a lower RBC product shelf-life compared to current practice. Respondents were not clear on the best non-DEHP vinyl material or RBC storage solution. Three European blood centres indicated they have developed non-DEHP transition plans. One challenge identified regarding the transition to non-DEHP is the extensive validation testing that will be required. CONCLUSION: Blood centres in Europe are concerned with meeting the sunset date for DEHP, considering that limited non-DEHP blood bag and RBC storage solutions are currently available. Banning DEHP in Europe, which may have global ramifications, represents a major challenge not yet fully understood by the transfusion medicine community.

Hemodynamic Comparison of Stent-Grafts for the Treatment of Aortoiliac Occlusive Disease.

PURPOSE: To compare the flow patterns and hemodynamics of the AFX stent-graft and the covered endovascular reconstruction of aortic bifurcation (CERAB) configuration using laser particle image velocimetry (PIV) experiments. MATERIALS AND METHODS: Two anatomically realistic aortoiliac phantoms were constructed using polydimethylsiloxane polymer. An AFX stent-graft with a transparent cover made with a new method was inserted into one phantom. A CERAB configuration using Atrium's Avanta V12 with transparent covers made with a previously established method was inserted into the other phantom, both modified stent-grafts were suitable for laser PIV, enabling visualization of the flow fields and quantification of time average wall shear stress (TAWSS), oscillatory shear index (OSI), and relative residence time (RRT). RESULTS: Disturbed flow was observed at the bifurcation region of the AFX, especially at the end systolic velocity (ESV) time-point where recirculation was noticeable due to vortical flow. In contrast, predominantly unidirectional flow was observed at the CERAB bifurcation. These observations were confirmed by the quantified hemodynamic results from PIV analysis where mean TAWSS of 0.078 Pa (range: 0.009-0.242 Pa) was significantly lower in AFX as compared with 0.229 Pa (range: 0.013-0.906 Pa) for CERAB (p<0.001). Mean OSI of 0.318 (range: 0.123-0.496) in AFX was significantly higher than 0.252 (range: 0.055-0.472) in CERAB (p<0.001). Likewise, mean RRT of 180 Pa-1 (range: 9-3603 Pa-1) in AFX was also significantly higher than 88 Pa-1 (range: 2-840 Pa-1) in CERAB (p=0.0086). CONCLUSION: In this in vitro study, the flow pattern of a modified AFX stent-graft was found to be more disturbed especially at the end systolic phase, its hemodynamic outcomes less desirable than CERAB configuration. CLINICAL RELEVANCE: While the AFX stent-graft has an advantage over the CERAB configuration in eliminating radial mismatch, and maintaining the anatomical bifurcation for future endovascular intervention, this in vitro study revealed that the associated lower TAWSS, higher OSI and RRT may predispose to thrombosis and are, thus, less desirable as compared to a CERAB configuration. Further investigation is warranted to confirm whether these findings translate into the clinical setting.

The application of computational modeling for risk prediction in type B aortic dissection.

OBJECTIVE: New tools are urgently needed to help with surgical decision-making in type B aortic dissection (TBAD) that is uncomplicated at the time of initial presentation. This narrative review aims to answer the clinical question, Can computational modeling be used to predict risk in acute and chronic Stanford TBAD? METHODS: The review (PROSPERO 2018 CRD42018104472) focused on risk prediction in TBAD. A comprehensive search of the Ovid MEDLINE database, using terms related to computational modeling and aortic dissection, was conducted to find studies of any form published between 1998 and 2018. Cohort studies, case series, and case reports of adults (older than 18 years) with computed tomography or magnetic resonance imaging diagnosis of TBAD were included. Computational modeling was applied in all selected studies. RESULTS: There were 37 studies about computational modeling of TBAD identified from the search, and the findings were synthesized into a narrative review. Computational modeling can produce numerically calculated values of stresses, pressures, and flow velocities that are difficult to measure in vivo. Hemodynamic parameters-high or low wall shear stress, high pressure gradient between lumens during the cardiac cycle, and high false lumen flow rate-have been linked to the pathogenesis of branch malperfusion and aneurysm formation by numerous studies. Considering the major outcomes of end-organ failure, aortic rupture, and stabilization and remodeling, hypotheses have been generated about inter-relationships of measurable parameters in computational models with observable anatomic and pathologic changes, resulting in specific clinical outcomes. CONCLUSIONS: There is consistency in study findings about computational modeling in TBAD, although a limited number of patients have been analyzed using various techniques. The mechanistic patterns of association found in this narrative review should be investigated in larger cohort prospective studies to further refine our understanding. It highlights the importance of patient-specific computational hemodynamic parameters in clinical decision-making algorithms. The current challenge is to develop and to test a risk assessment method that can be used by clinicians for TBAD.

Morphology and Hemodynamics in Isolated Common Iliac Artery Aneurysms Impacts Proximal Aortic Remodeling.

Objective- Isolated common iliac artery aneurysms (CIAA) are rare. Their prognosis and influence on aortoiliac blood flow and remodeling are unclear. We evaluated the hypotheses that morphology at and distal to the aortic bifurcation, together with the associated hemodynamic changes, influence both the natural history of CIAA and proximal aortic remodeling. Approach and Results- Twenty-five isolated CIAAs (15 intact, 10 ruptured), in 23 patients were reconstructed and analyzed with computational fluid dynamics: all showed abnormal flow. Then we studied a series of 24 hypothetical aortoiliac geometries in silico with varying abdominal aortic deflection and aortic bifurcation angles: key findings were assessed in an independent validation cohort of 162 patients. Wall shear stress in isolated unilateral CIAAs was lower than the contralateral common iliac artery, 0.38±0.33 Pa versus 0.61±0.24 Pa, inversely associated with CIAA diameter ( P<0.001) and morphology (high shear stress in variants distal to a sharp kink). Rupture usually occurred in regions of elevated low and oscillatory shear with a wide aortic bifurcation angle. Abdominal aortas deflected towards the CIAA for most unilateral isolated CIAAs (14/21). In silico, wider bifurcation angles created high focal regions of low and oscillatory shear in the common iliac artery. The associations of unilateral CIAA with aortic deflection and common iliac artery diameter with bifurcation angle were confirmed in the validation cohort. Conclusions- Decreasing wall shear stress is strongly associated with CIAA progression (larger aneurysms and rupture), whereas abnormal blood flow in the CIAA seems to promote proximal aortic remodeling, with adaptive lateral deflection of the abdominal aorta towards the aneurysmal side.

Morphology and Computational Fluid Dynamics Support a Novel Classification of Common Iliac Aneurysms.

OBJECTIVE: Isolated common iliac artery aneurysms (CIAAs) are uncommon, and evidence concerning their development, progression, and management is weak. The objective was to describe the morphology and haemodynamics of isolated CIAAs in a retrospective study. METHODS: Initially, a series of 25 isolated CIAAs (15 intact, 10 ruptured) in 23 patients were gathered from multiple centres, reconstructed from computed tomography, and then morphologically classified and analysed with computational fluid dynamics. The morphological classification was applied in a separate, consecutive cohort of 162 patients assessed for elective aorto-iliac intervention, in which 55 patients had intact CIAAs. RESULTS: In the isolated CIAA cohort, three distinct morphologies were identified: complex (involving a bifurcation); fusiform; and kinked (distal to a sharp bend in the CIA), with mean diameters of 90.3, 48.3, and 31.7 mm, and mean time averaged wall shear stresses of 0.16, 0.31, and 0.71 Pa, respectively (both analysis of variance p values < .001). Kinked cases vs. fusiform cases had less thrombus and favourable haemodynamics similar to the non-aneurysmal contralateral common iliac artery (CIA). Ruptured isolated CIAAs were large (mean diameter 87.5 mm, range 55.5-138.0 mm) and predominantly complex. The mean CIA length for aneurysmal arteries was greatest in kinked cases followed by complex and fusiform (100.8 mm, 91.1 mm, and 80.6 mm, respectively). The morphological classification was readily applicable to a separate elective patient cohort. CONCLUSION: A new morphological categorisation of CIAAs is proposed. Potentially this is associated with both haemodynamics and clinical course. Further research is required to determine whether the kinked CIAA is protected haemodynamically from aneurysm progression and to establish the wider applicability of the categorisation presented.

Surgical Decision Making in Uncomplicated Type B Aortic Dissection: A Survey of Australian/New Zealand and European Surgeons.

OBJECTIVE: There is controversy about the role of pre-emptive thoracic endovascular aortic repair (TEVAR) in uncomplicated type B aortic dissection (TBAD). The aim was to understand expert opinions and the factors influencing decision making. METHODS: In 2018, surgeons from Australia/New Zealand (ANZ) and Europe (EUR) were contacted to participate in an online survey which comprised questions about preferences for pre-emptive TEVAR, followed by five case scenarios, and two ranking questions for anatomical and technical risk factors respectively. Case 1 was designed to favour TEVAR in a hypertensive patient with partial false lumen thrombosis and large diameter (aortic ≥ 40 mm, false lumen ≥ 22 mm). Case 2 had no risk factors mandating TEVAR, according to current evidence. Cases 3, 4, and 5 were designed to test one risk factor respectively, large entry tear on the inner aortic curvature (≥10 mm), partial false lumen thrombosis, and large diameter alone. RESULTS: There were 75 responses, 42 from EUR and 33 from ANZ. Almost half of surgeons (49.3%) endorsed pre-emptive TEVAR with 82.3% preferring to perform TEVAR in the subacute phase. In Case 1 and 5, 58.3% and 52.8% of surgeons respectively chose TEVAR, the highest rates obtained in the survey. Cases 1 and 5 included large diameters ≥40 mm, which were ranked the highest in importance when surgeons considered anatomical risk factors. Surgeons who recommend pre-emptive TEVAR were more likely to choose TEVAR in both Case 1 (83.3% vs. 33.3%, p < .001, 95% CI 27.6%-65.8%) and Case 5 (69.4% vs. 38.2%, p = .008, 95% CI 8.2%-50.0%). CONCLUSION: In this survey about uncomplicated TBAD, about half of surgeons recommended pre-emptive TEVAR in selected cases. The surgeon's predisposition towards intervention and large diameters appear to be the most influential factors in decision making. These findings underline the uncertainty in today's practice and emphasise the need for better predictive tools.

Biomechanical Assessment Predicts Aneurysm Related Events in Patients with Abdominal Aortic Aneurysm.

OBJECTIVE: To test whether aneurysm biomechanical ratio (ABR; a dimensionless ratio of wall stress and wall strength) can predict aneurysm related events. METHODS: In a prospective multicentre clinical study of 295 patients with an abdominal aortic aneurysm (AAA; diameter ≥ 40 mm), three dimensional reconstruction and computational biomechanical analyses were used to compute ABR at baseline. Participants were followed for at least two years and the primary end point was the composite of aneurysm rupture or repair. RESULTS: The majority were male (87%), current or former smokers (86%), most (72%) had hypertension (mean ± standard deviation [SD] systolic blood pressure 140 ± 22 mmHg), and mean ± SD baseline diameter was 49.0 ± 6.9 mm. Mean ± SD ABR was 0.49 ± 0.27. Participants were followed up for a mean ± SD of 848 ± 379 days and rupture (n = 13) or repair (n = 102) occurred in 115 (39%) cases. The number of repairs increased across tertiles of ABR: low (n = 24), medium (n = 34), and high ABR (n = 44) (p = .010). Rupture or repair occurred more frequently in those with higher ABR (log rank p = .009) and ABR was independently predictive of this outcome after adjusting for diameter and other clinical risk factors, including sex and smoking (hazard ratio 1.41; 95% confidence interval 1.09-1.83 [p = .010]). CONCLUSION: It has been shown that biomechanical ABR is a strong independent predictor of AAA rupture or repair in a model incorporating known risk factors, including diameter. Determining ABR at baseline could help guide the management of patients with AAA.

Healthcare before Welfare States: Hospitals in Early Twentieth Century England and France.

Following the. Second World War, many west European nations developed welfare states to enhance the health and security of their populations, but the systems that were created differed significantly in form and function. This article will provide a comparative overview of the development of hospital services in urban England and France in the first forty years of the 20th century using evidence from two case study cities to enhance our understanding of how these welfare systems developed. It will consider the structure of the two hospital systems; governance and accountability; institutional finance; patients; and the role of the central and local state to argue that the maintenance of two separate providers and the exclusion of hospitals from state health insurance in England prompted a different set of responses to the delivery of hospital care compared to what was found in the unified and increasingly state-funded French system.

Modelling large scale artery haemodynamics from the heart to the eye in response to simulated microgravity.

We investigated variations in haemodynamics in response to simulated microgravity across a semi-subject-specific three-dimensional (3D) continuous arterial network connecting the heart to the eye using computational fluid dynamics (CFD) simulations. Using this model we simulated pulsatile blood flow in an upright Earth gravity case and a simulated microgravity case. Under simulated microgravity, regional time-averaged wall shear stress (TAWSS) increased and oscillatory shear index (OSI) decreased in upper body arteries, whilst the opposite was observed in the lower body. Between cases, uniform changes in TAWSS and OSI were found in the retina across diameters. This work demonstrates that 3D CFD simulations can be performed across continuously connected networks of small and large arteries. Simulated results exhibited similarities to low dimensional spaceflight simulations and measured data-specifically that blood flow and shear stress decrease towards the lower limbs and increase towards the cerebrovasculature and eyes in response to simulated microgravity, relative to an upright position in Earth gravity.

Comparison of computational fluid dynamics with transcranial Doppler ultrasound in response to physiological stimuli.

Cerebrovascular haemodynamics are sensitive to multiple physiological stimuli that require synergistic response to maintain adequate perfusion. Understanding haemodynamic changes within cerebral arteries is important to inform how the brain regulates perfusion; however, methods for direct measurement of cerebral haemodynamics in these environments are challenging. The aim of this study was to assess velocity waveform metrics obtained using transcranial Doppler (TCD) with flow-conserving subject-specific three-dimensional (3D) simulations using computational fluid dynamics (CFD). Twelve healthy participants underwent head and neck imaging with 3 T magnetic resonance angiography. Velocity waveforms in the middle cerebral artery were measured with TCD ultrasound, while diameter and velocity were measured using duplex ultrasound in the internal carotid and vertebral arteries to calculate incoming cerebral flow at rest, during hypercapnia and exercise. CFD simulations were developed for each condition, with velocity waveform metrics extracted in the same insonation region as TCD. Exposure to stimuli induced significant changes in cardiorespiratory measures across all participants. Measured absolute TCD velocities were significantly higher than those calculated from CFD (P range < 0.001-0.004), and these data were not correlated across conditions (r range 0.030-0.377, P range 0.227-0.925). However, relative changes in systolic and time-averaged velocity from resting levels exhibited significant positive correlations when the distinct techniques were compared (r range 0.577-0.770, P range 0.003-0.049). Our data indicate that while absolute measures of cerebral velocity differ between TCD and 3D CFD simulation, physiological changes from resting levels in systolic and time-averaged velocity are significantly correlated between techniques.

3D printing of heart valves.

3D printing technologies have the potential to revolutionize the manufacture of heart valves through the ability to create bespoke, complex constructs. In light of recent technological advances, we review the progress made towards 3D printing of heart valves, focusing on studies that have utilised these technologies beyond manufacturing patient-specific moulds. We first overview the key requirements of a heart valve to assess functionality. We then present the 3D printing technologies used to engineer heart valves. By referencing International Organisation for Standardisation (ISO) Standard 5840 (Cardiovascular implants - Cardiac valve prostheses), we provide insight into the achieved functionality of these valves. Overall, 3D printing promises to have a significant positive impact on the creation of artificial heart valves and potentially unlock full complex functionality.

Natural, synthetic and commercially-available biopolymers used to regenerate tendons and ligaments.

Tendon and ligament (TL) injuries affect millions of people annually. Biopolymers play a significant role in TL tissue repair, whether the treatment relies on tissue engineering strategies or using artificial tendon grafts. The biopolymer governs the mechanical properties, biocompatibility, degradation, and fabrication method of the TL scaffold. Many natural, synthetic and hybrid biopolymers have been studied in TL regeneration, often combined with therapeutic agents and minerals to engineer novel scaffold systems. However, most of the advanced biopolymers have not advanced to clinical use yet. Here, we aim to review recent biopolymers and discuss their features for TL tissue engineering. After introducing the properties of the native tissue, we discuss different types of natural, synthetic and hybrid biopolymers used in TL tissue engineering. Then, we review biopolymers used in commercial absorbable and non-absorbable TL grafts. Finally, we explain the challenges and future directions for the development of novel biopolymers in TL regenerative treatment.

Novel hybrid biocomposites for tendon grafts: The addition of silk to polydioxanone and poly(lactide-co-caprolactone) enhances material properties, in vitro and in vivo biocompatibility.

Biopolymers play a critical role as scaffolds used in tendon and ligament (TL) regeneration. Although advanced biopolymer materials have been proposed with optimised mechanical properties, biocompatibility, degradation, and processability, it is still challenging to find the right balance between these properties. Here, we aim to develop novel hybrid biocomposites based on poly(p-dioxanone) (PDO), poly(lactide-co-caprolactone) (LCL) and silk to produce high-performance grafts suitable for TL tissue repair. Biocomposites containing 1-15% of silk were studied through a range of characterisation techniques. We then explored biocompatibility through in vitro and in vivo studies using a mouse model. We found that adding up to 5% silk increases the tensile properties, degradation rate and miscibility between PDO and LCL phases without agglomeration of silk inside the composites. Furthermore, addition of silk increases surface roughness and hydrophilicity. In vitro experiments show that the silk improved attachment of tendon-derived stem cells and proliferation over 72 h, while in vivo studies indicate that the silk can reduce the expression of pro-inflammatory cytokines after six weeks of implantation. Finally, we selected a promising biocomposite and created a prototype TL graft based on extruded fibres. We found that the tensile properties of both individual fibres and braided grafts could be suitable for anterior cruciate ligament (ACL) repair applications.

Silane-modified hydroxyapatite nanoparticles incorporated into polydioxanone/poly(lactide-co-caprolactone) creates a novel toughened nanocomposite with improved material properties and in vivo inflammatory responses.

The interface tissue between bone and soft tissues, such as tendon and ligament (TL), is highly prone to injury. Although different biomaterials have been developed for TL regeneration, few address the challenges of the TL-bone interface. Here, we aim to develop novel hybrid nanocomposites based on poly(p-dioxanone) (PDO), poly(lactide-co-caprolactone) (LCL), and hydroxyapatite (HA) nanoparticles suitable for TL-bone interface repair. Nanocomposites, containing 3-10% of both unmodified and chemically modified hydroxyapatite (mHA) with a silane coupling agent. We then explored biocompatibility through in vitro and in vivo studies using a subcutaneous mouse model. Through different characterisation tests, we found that mHA increases tensile properties, creates rougher surfaces, and reduces crystallinity and hydrophilicity. Morphological observations indicate that mHA nanoparticles are attracted by PDO rather than LCL phase, resulting in a higher degradation rate for mHA group. We found that adding the 5% of nanoparticles gives a balance between the properties. In vitro experiments show that osteoblasts' activities are more affected by increasing the nanoparticle content compared with fibroblasts. Animal studies indicate that both HA and mHA nanoparticles (10%) can reduce the expression of pro-inflammatory cytokines after six weeks of implantation. In summary, this work highlights the potential of PDO/LCL/HA nanocomposites as an excellent biomaterial for TL-bone interface tissue engineering applications.