The activities are aimed at:

• defining the etiopathogenetic mechanisms of musculoskeletal diseases of great social impact
• identifying the local and systemic changes that these diseases and/or their treatment determine in the organism
• studying molecules able to selectively inhibit specific functions, in order to promote the repair/regeneration of damaged osteocartilaginous tissue
• developing innovative therapeutic methods and strategies aimed at preventing/treating osteoarthritis
• identifying biomarkers predictive of the course of the main osteoarticular diseases such as osteoarthritis and rheumatoid arthritis
• defining the biological bases of individual response to drugs.

Specific activities

Characterization of biological markers of inflammation, of activity and progression of osteoarticular diseases and of therapeutic response

• ex vivo studies on synovial tissue of patients with osteoarthritis-OA and rheumatoid arthritis-RA to analyze molecular mechanisms and cell populations involved in the development of the inflammatory and pain response
• studies on cell models (of osteoarticular and/or mesenchymal derivation), prepared with cells isolated from patients with OA or RA, to identify possible therapeutic targets (with particular regard to the signaling mechanisms that control inflammation and degeneration of cartilage tissue) or to evaluate the effect of molecules, nutraceuticals or drugs for OA and/or RA or other osteoaticular diseases (viability, proliferation, cytotoxic activity, apoptosis and anti-inflammatory activity)
• evaluations of soluble factors released in the synovial fluid and/or in the plasma, of relevance for the etiopathogenesis of OA, RA and genetic pathologies with cartilage involvement
• evaluation of immune and bone cells interactions
• advanced preclinical studies (cell therapy) on animal models such as cell therapies for the treatment of specific diseases (eg rheumatic diseases, osteoarthritis, muscular dystrophies) and characterization of the role of specific genes and proteins involved in the pathological process using transgenic animal models (in coll. with the Unit Preclinical and Surgical Studies).

Advanced histological analysis in the rheumatological field

Since 2003, advanced histological analysis with rheumatological orientation has been carried out on synovial tissue samples received from the IOR Clinical Units.

This  activity provides for histological and immunohistochemical analyses on synovial tissue collected during surgical procedures or arthroscopy examinations, and the evaluation by means of a score, carried out jointly by Anatomo-Pathologists and Rheumatologists.

This activity has the primary objective of supplying a qualified histological study service in the rheumatological field.

The activities are focused on:

• morphological, structural and functional assessments of cell-biomaterial interactions, by using human and animal derived cell populations (mononuclear cells, mesenchymal cells from bone marrow or adipose tissue, cells of the musculoskeletal system and/or cell lines)
• studies on  2D/3D culture models, in static and dynamic conditions, under mechanical stimulation, with variable oxygen concentrations
• preparation of customized scaffolds functionalised with cells, through a 3D bioprinting platform, for applications in regenerative medicine of the musculoskeletal system.

Specific activities

Tissue regeneration

• isolation, growth and differentiation of human and animal derived cells (mononuclear cells, mesenchymal cells obtained from bone marrow or adipose tissue, chondrocytes, osteoblasts, synoviocytes, tenocytes, ligament cells) and/or cell lines
• phenotypic and functional characterization of single or co-cultured cell populations, maintained in 2D, 3D static conditions
• dynamic growth systems using bioreactors with variable oxygen concentrations
• 3D growth systems under computer-controlled mechanical stimulations. 

Evaluation and monitoring of the biosafety of products for cell therapy during in vitro manipulation

• evaluation of cell replication potential and cell proliferation kinetics
• genetic alteration studies during cellular aging and influence of oxidative stress 
• DNA damage analysis (microsatellite instability analysis, histone H2A phosphorylation) and activation of genes involved in DNA repair systems
• telomere length evaluation and quantification of the telomerase enzyme activity and expression.

Structural, morphological and functional evaluations of interactions between cells and biomaterials (scaffolds)

• analysis of the interactions between chondrocytes and osteoblasts, mononuclear or mesenchymal cells with different biomaterials, both in basal conditions and during chondrogenic or osteogenic differentiation
• realization of customized and cell functionalized scaffolds for regenerative medicine applications on the musculoskeletal system, through a bioprinting platform, which allows three-dimensional (3D) structure printing of natural and synthetic polymers or hydrogel polymerization also using radiological images acquired through a dual Energy TAC.

The research activity of the "Physiopathology and regeneration of osteoarticular tissue" Unit (Head Dr. Gina Lisignoli) is aimed at studying musculoskeletal tissues which, due to ageing, trauma and/or degenerative diseases, lose their original characteristics and need to be regenerated or treated with cell therapies. The simple structure is mainly concerned with: studying innovative cell therapies focusing on possible solutions to mimic the development of degenerative diseases, such as osteoarthritis, and counteracting the inflammatory process; regenerative medicine using technologies involving the development of innovative biomaterials (3-dimensional constructs -3D) which, combined with cells, are able to promote the regeneration of damaged osteoarticular tissues.

In particular, the main research activities are aimed at: evaluation of the potential of mesenchymal cells to regenerate damaged joint tissues and to counteract the action of immune system cells (macrophages, lymphocytes) involved in the inflammatory process; validation of preclinical in vitro models of degenerative diseases (osteoarthritis) using cellular co-cultures to recreate the joint microenvironment (synovium, cartilage, bone) under both static and dynamic conditions; evaluation of biomarkers of anabolic and catabolic processes in joint tissues; identification of strategies for osteoarticular tissue regeneration using innovative biomaterials combined with 3D printing technologies; evaluation of cell-biomaterial interactions: studies on the ability of mesenchymal cells to differentiate into mature tissues (bone and cartilage) using dynamic growth systems (bioreactor) and different oxygen tensions; evaluation of the effect of innovative therapies, such as ultrasound, on cell differentiation and the inflammatory response (2D and 3D models).

On these research topics, students and PhD students who need to write their degree and PhD theses may be admitted.

Researchers and Collaborators: Dott.ssa Elena Gabusi Dirigente Biologo, Dott.ssa Cristina Manferdini, Tecnico Sanitario di Laboratorio Biomedico, Dott.ssa Yasmin Saleh Borsista, Dott. Enrico Lenzi Borsista, Ing. Diego Trucco PhD Candidate.

Active research projects:

• 2019-2023, European Project H2020 "Advanced nanocomposite MAterials fOr in situ treatment and ultrasound-mediated management of Osteoarthritis" (ADMAIORA) (n. 814413). IRCCS Rizzoli Orthopaedic Institute Responsible and for WP6. Web site: https://www.admaiora-project.com/, https://cordis.europa.eu/project/id/814413/it.
• 2021-2025 AIRC MFAG 2020 project ID 24932: "Study of the mechanisms underlying progression from indolent monoclonal gammopathy to multiple myeloma". Partners in the project research group.

Completed research projects:

• 2017-2019, Project of the Ministry of Foreign Affairs, Executive programme for scientific and technological cooperation between the Italian Republic and the Republic of India, "Development of osteochondral tissue using 3 D printing technology" (no. IN17MO03), Italian responsible.
• 2015-2019, European Project H2020 "Clinical trial of autologous adipose-derived mesenchymal stromal cells (ASC) in the treatment of mild to moderate osteoarthritis" ADIPOA2 (n.643809), responsible for IOR and WP4. 2008-2011, Emilia Romagna Region-University of Bologna, project: “Regenerative medicine in osteo-articular diseases”, WP2 responsible.
• 2013-2016, Emilia-Romagna Region-University of Bologna Project "Regenerative medicine of cartilage and bone", Operational Unit in WP2 responsible. 2005-2007, Targeted research project, Ministry of Health “Use of mesenchymal cells in tissue engineering for the prevention of cartilage damage”, Operational Unit responsible.
• 2001-2003, Target research project, Ministry of Health: Biological and genetic markers of osteoarthritis severity, Operational Unit responsible.

Scientific Societies: International Cartilage Regeneration and Joint Preservation Society (ICRS); Osteoarthritis Research Society International (OARSI); Stem Cell Research Italy (SCR-Italy).

Patents:

• 2020, "Material and system for the therapeutic treatment of joints" IT201900002697A1, 2020-08-25, Scuola Superiore di Studi Universitari e di Perfezionamento Sant’Anna [IT].
• 2020, "Pharmaceutical compositions including amide derivatives of hyaluronic acid for use in the treatment of bone traumas, in particular in patients with osteopenia or osteoporosis", IT201900009933A1, 2020-12-24, Fidia Farmaceutici [IT].
• 2016, "New molecules for bone tissue regeneration" US10016444B2 (A1), 2018-07-10, Istituto Ortopedico Rizzoli [IT].
• 1997: "Device for the support and containment of biological cell cultures" IT1285959B1 (A1), 1998-06-26, Istituto Ortopedico Rizzoli [IT].