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1.
Health Policy ; 146: 105117, 2024 Jun 23.
Article in English | MEDLINE | ID: mdl-38972144

ABSTRACT

Unlike many other industries, which are characterized by a more significant presence of men than women, the healthcare sector has a clear majority of women. However, even if at the non-executive level, the percentage of women is extremely higher than that of men, at the executive level, this percentage is completely overturned, generating the so-called glass ceiling effect. Despite extensive research on gender diversity and its impact on financial metrics, few studies have focused on clinical measures. To bridge this research gap, the article analyzes the relationship between gender diversity and healthcare metrics. We developed an econometric model for unbalanced panel data by performing a random effect and a quantile regression analysis, which test the relationship between gender diversity and the average length of stay (LOS), controlling for structural and clinical metrics. We find that, in general, a higher percentage of women in non-executive positions is related to an increase in LOS. Conversely, a higher rate of women in executive positions is related to a lower level of LOS. Empirical evidence supports the relevance of including human resources strategies to increase the number of women at executive managerial positions. However, the study highlights also the necessity to consider how to make the public health sector positions more appealing for men.

2.
Methods Mol Biol ; 2598: 325-336, 2023.
Article in English | MEDLINE | ID: mdl-36355302

ABSTRACT

Osteochondral explants harvested from different species are valuable preclinical ex vivo models for tissue engineering research. In this chapter, we describe the isolation of osteochondral plugs from bovine stifle joints, followed by defect creation, and plug preparation in a straightforward manner before mechanical loading using a compression and shear bioreactor. The method can be adapted to isolate osteochondral plugs from any animal species and to load explants in any type of bioreactor.


Subject(s)
Cartilage, Articular , Cattle , Animals , Knee Joint , Tissue Engineering/methods , Bioreactors , Chondrocytes
3.
Acta Biomater ; 105: 170-179, 2020 03 15.
Article in English | MEDLINE | ID: mdl-31982592

ABSTRACT

Current treatments for cartilage lesions are often associated with fibrocartilage formation and donor site morbidity. Mechanical and biochemical stimuli play an important role in hyaline cartilage formation. Biocompatible scaffolds capable of transducing mechanical loads and delivering bioactive instructive factors may better support cartilage regeneration. In this study we aimed to test the interplay between mechanical and FGF-18 mediated biochemical signals on the proliferation and differentiation of primary bovine articular chondrocytes embedded in a chondro-conductive Fibrin-Hyaluronan (FB/HA) based hydrogel. Chondrocytes seeded in a Fibrin-HA hydrogel, with or without a chondro-inductive, FGFR3 selective FGF18 variant (FGF-18v) were loaded into a joint-mimicking bioreactor applying controlled, multi-axial movements, simulating the natural movements of articular joints. Samples were evaluated for DNA content, sulphated glycosaminoglycan (sGAG) accumulation, key chondrogenic gene expression markers and histology. Under moderate loading, samples produced particularly significant amounts of sGAG/DNA compared to unloaded controls. Interestingly there was no significant effect of FGF-18v on cartilage gene expression at rest. Following moderate multi-axial loading, FGF-18v upregulated the expression of Aggrecan (ACAN), Cartilage Oligomeric Matrix Protein (COMP), type II collagen (COL2) and Lubricin (PRG4). Moreover, the combination of load and FGF-18v, significantly downregulated Matrix Metalloproteinase-9 (MMP-9) and Matrix Metaloproteinase-13 (MMP-13), two of the most important factors contributing to joint destruction in OA. Biomimetic mechanical signals and FGF-18 may work in concert to support hyaline cartilage regeneration and repair. STATEMENT OF SIGNIFICANCE: Articular cartilage has very limited repair potential and focal cartilage lesions constitute a challenge for current standard clinical procedures. The aim of the present research was to explore novel procedures and constructs, based on biomaterials and biomechanical algorithms that can better mimic joints mechanical and biochemical stimulation to promote regeneration of damaged cartilage. Using a hydrogel-based platform for chondrocyte 3D culture revealed a synergy between mechanical forces and growth factors. Exploring the mechanisms underlying this mechano-biochemical interplay may enhance our understanding of cartilage remodeling and the development of new strategies for cartilage repair and regeneration.


Subject(s)
Cartilage, Articular/cytology , Chondrocytes/cytology , Chondrogenesis , Fibrin/pharmacology , Fibroblast Growth Factors/pharmacology , Hyaluronic Acid/pharmacology , Hydrogels/pharmacology , Animals , Cattle , Chondrocytes/drug effects , Chondrogenesis/drug effects , DNA/metabolism , Gene Expression Regulation/drug effects , Glycosaminoglycans/metabolism , Phenotype , RNA, Messenger/genetics , RNA, Messenger/metabolism , Stress, Mechanical , Weight-Bearing
4.
Acta Biomater ; 101: 293-303, 2020 01 01.
Article in English | MEDLINE | ID: mdl-31726249

ABSTRACT

Biomaterials play a pivotal role in cell-free cartilage repair approaches, where cells must migrate through the scaffold, fill the defect, and then proliferate and differentiate facilitating tissue remodeling. Here we used multiple assays to test the influence of chemokines and growth factors on cell migration and cartilage repair in two different hyaluronan (HA)-based hydrogels. We first investigated bone marrow Mesenchymal Stromal Cells (BMSC) migration in vitro, in response to different concentrations of platelet-derived growth factor-BB (PDGF-BB), chemokine ligand 5 (CCL5/RANTES) and stromal cell-derived factor 1 (SDF-1), using a 3D spheroid-based assay. PDGF-BB was selected as most favourable chemotactic agent, and MSC migration was assessed in the context of physical impediment to cell recruitment by testing Fibrin-HA and HA-Tyramine hydrogels of different cross-linking densities. Supplementation of PDGF-BB stimulated progressive migration of MSC through the gels over time. We then investigated in situ cell migration into the hydrogels with and without PDGF-BB, using a cartilage-bone explant model implanted subcutaneously in athymic mice. In vivo studies show that when placed into an osteochondral defect, both hydrogels supported endogenous cell infiltration and provided an amenable microenvironment for cartilage production. These processes were best supported in Fibrin-HA hydrogel in the absence of PDGF-BB. This study used an advanced preclinical testing platform to select an appropriate microenvironment provided by implanted hydrogels, demonstrating that HA-based hydrogels can promote the initial and critical step of endogenous cell recruitment and circumvent some of the clinical challenges in cartilage tissue repair. STATEMENT OF SIGNIFICANCE: The challenge of articular cartilage repair arises from its complex structure and architecture, which confers the unique mechanical behavior of the extracellular matrix. The aim of our research is to identify biomaterials for implants that can support migration of endogenous stem and progenitor cell populations from cartilage and bone tissue, in order to permanently replace damaged cartilage with the original hyaline structure. Here, we present an in vitro 3D spheroid-based migration assay and an osteochondral defect model, which provide the opportunity to assess biomaterials and biomolecules, and to get stronger experimental evidence of the not well-characterized dynamic process of endogenous cells colonization in an osteochondral defect. Furthermore, the delicate step of early cell migration into biomaterials towards functional tissue engineering is reproduced. These tests can be used for pre-clinical testing of newly developed material designs in the field of scaffold engineering.


Subject(s)
Biomimetic Materials/pharmacology , Cartilage, Articular/metabolism , Extracellular Matrix/metabolism , Hyaluronic Acid/pharmacology , Hydrogels/pharmacology , Adolescent , Aged , Animals , Becaplermin/pharmacology , Cartilage, Articular/drug effects , Cattle , Cell Movement/drug effects , Chondrogenesis/drug effects , Cross-Linking Reagents/pharmacology , Extracellular Matrix/drug effects , Humans , Mesenchymal Stem Cells/cytology , Mesenchymal Stem Cells/drug effects , Middle Aged , Spheroids, Cellular/drug effects , Tyramine/pharmacology , Wound Healing/drug effects
5.
Acta Biomater ; 81: 256-266, 2018 11.
Article in English | MEDLINE | ID: mdl-30273741

ABSTRACT

Surgical procedures such as microfracture or autologous chondrocyte implantation have been used to treat articular cartilage lesions; however, repair often fails in terms of matrix organization and mechanical behaviour. Advanced biomaterials and tissue engineered constructs have been developed to improve cartilage repair; nevertheless, their clinical translation has been hampered by the lack of reliable in vitro models suitable for pre-clinical screening of new implants and compounds. In this study, an osteochondral defect model in a bioreactor that mimics the multi-axial motion of an articulating joint, was developed. Osteochondral explants were obtained from bovine stifle joints, and cartilage defects of 4 mm diameter were created. The explants were used as an interface against a ceramic ball applying dynamic compressive and shear loading. Osteochondral defects were filled with chondrocytes-seeded fibrin-polyurethane constructs and subjected to mechanical stimulation. Cartilage viability, proteoglycan accumulation and gene expression of seeded chondrocytes were compared to free swelling controls. Cells within both cartilage and bone remained viable throughout the 10-day culture period. Loading did not wear the cartilage, as indicated by histological evaluation and glycosaminoglycan release. The gene expression of seeded chondrocytes indicated a chondrogenic response to the mechanical stimulation. Proteoglycan 4 and cartilage oligomeric matrix protein were markedly increased, while mRNA ratios of collagen type II to type I and aggrecan to versican were also enhanced. This mechanically stimulated osteochondral defect culture model provides a viable microenvironment and will be a useful pre-clinical tool to screen new biomaterials and biological regenerative therapies under relevant complex mechanical stimuli. STATEMENT OF SIGNIFICANCE: Articular cartilage lesions have a poor healing capacity and reflect one of the most challenging problems in orthopedic clinical practice. The aim of current research is to develop a testing system to assess biomaterials for implants, that can permanently replace damaged cartilage with the original hyaline structure and can withstand the mechanical forces long term. Here, we present an osteochondral ex vivo culture model within a cartilage bioreactor, which mimics the complex motion of an articulating joint in vivo. The implementation of mechanical forces is essential for pre-clinical testing of novel technologies in the field of cartilage repair, biomaterial engineering and regenerative medicine. Our model provides a unique opportunity to investigate healing of articular cartilage defects in a physiological joint-like environment.


Subject(s)
Biocompatible Materials , Cartilage, Articular/metabolism , Chondrocytes/metabolism , Chondrogenesis , Models, Biological , Tissue Engineering , Animals , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Cartilage Diseases/metabolism , Cartilage Diseases/pathology , Cartilage Diseases/therapy , Cartilage, Articular/pathology , Cattle , Chondrocytes/pathology
6.
Int J Qual Health Care ; 23(3): 324-30, 2011 Jun.
Article in English | MEDLINE | ID: mdl-21454349

ABSTRACT

OBJECTIVE: This paper reports the measurement of technical efficiency of Tuscan Local Health Authorities and its relationship with quality and appropriateness of care. DESIGN: First, a bias-corrected measure of technical efficiency was developed using the bootstrap technique applied to data envelopment analysis. Then, correlation analysis was used to investigate the relationships among technical efficiency, quality and appropriateness of care. SETTING AND PARTICIPANTS: These analyses have been applied to the Local Health Authorities of Tuscany Region (Italy), which provide not only hospital inpatient services, but also prevention and primary care. All top managers of Tuscan Local Health Authorities were involved in selection of the inputs and outputs for calculating technical efficiency. MAIN OUTCOME MEASURES: The main measure used in this study are volume, quality and appropriateness indicators monitored by the multidimensional performance evaluation system developed in the Tuscany Region. RESULTS: On average, Tuscan Local Health Authorities experienced 14(%) of bias-corrected inefficiency in 2007. Correlation analyses showed a significant negative correlation between per capita costs and overall performance. No correlation was found in 2007 between technical efficiency and overall performance or between technical efficiency and per capita costs. CONCLUSIONS: Technical efficiency cannot be considered as an extensive measure of healthcare performance, but evidence shows that Tuscan Local Health Authorities have room for improvement in productivity levels. Indeed, correlation findings suggest that, to pursue financial sustainability, Local Health Authorities mainly have to improve their performance in terms of quality and appropriateness.


Subject(s)
Efficiency, Organizational/economics , Health Care Costs , Primary Health Care/organization & administration , Quality of Health Care/organization & administration , Italy , Models, Economic , Primary Health Care/economics , Quality Indicators, Health Care , Quality of Health Care/economics , Workforce
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