CytotoxicityRAISENCT07671521
Biological Evaluation of Orthopedic Materials: An In Vitro Study Using Patient-Derived Human Samples
An observational study of Cytotoxicity, run by Stefano Zaffagnini at 1 site in Italy.
Trial summary
The anterior cruciate ligament (ACL) is the primary stabilizer of the knee joint, and ACL injuries are highly prevalent, particularly among physically active and athletic individuals. Read more about this study
- Who is it for?
- Ages 18 to 80 years
- Conditions the study is for
- Cytotoxicity
- How many people
- 50 participants
- Where
- 1 siteItaly
- Study dates
- Sep 2026to Jun 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 80 years
- All sexes
- Adult, Older adult
Study population: Subjects will be recruited among patients admitted to the IRCCS Istituto Ortopedico Rizzoli and scheduled for total knee arthroplasty for the treatment of chondral defects and/or undergoing regenerative infiltrative therapies with BMC and PRP. For the study, biological material obtained during the surgical removal of femoral condyles, tibial plateaus and synovial membranes, as well as during implantation of the prosthetic components, will be used. For BMC and PRP, only waste material not required for the surgical procedures will be collected. The recovery of such material will be performed during routine clinical practice by the medical staff of the Orthopaedic and Trauma Clinic II.
Who may be able to join
- Age 18-80 years, male or female Primary tricompartmental osteoarthritis Body Mass Index (BMI) < 35 Kellgren-Lawrence grade III-IV osteoarthritis Written informed consent
- Age 18-70 years Medial compartment knee osteoarthritis (Kellgren-Lawrence grade II-III for >4 months) Failure of ≥6 months of conservative treatment (NSAIDs/analgesics, hyaluronic acid, corticosteroid or PRP injections) Written informed consent
- Age 18-65 years Clinical signs and symptoms of knee cartilage degeneration Radiographic or MRI evidence of degeneration (Kellgren-Lawrence grade II-IV) Hemoglobin > 11 g/dL Platelet count > 150,000/mm³ No clinically relevant ECG abnormalities Written informed consent
Who cannot join
- Previous partial knee arthroplasty or cartilage repair/regenerative procedures Rheumatoid arthritis or chronic corticosteroid/immunosuppressive therapy Positive testing for HIV, HBV or HCV infection Concentrated bone marrow (BMC) samples
- Patients of both sexes providing written informed consent and presenting with the following characteristics:
- Inability to provide informed consent Knee trauma within the previous 6 months Malignancy, rheumatic disease, uncontrolled diabetes, uncontrolled thyroid disorders Alcohol or drug abuse BMI > 35 Intra-articular injections within the previous 6 months Knee surgery within the previous 12 months HIV, HBV or HCV positivity Platelet-rich plasma (PRP) samples
- Patients of both sexes with degenerative cartilage disease of the knee.
- Rheumatoid arthritis or chronic corticosteroid/immunosuppressive therapy Uncontrolled diabetes Hematological disorders or anticoagulant/antiplatelet therapy Thyroid metabolic disorders Alcohol, drug or medication abuse NSAID use within 3 days prior to blood draw Cardiovascular disease contraindicating a 150 mL blood draw HIV, HBV or HCV positivity
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site
IRCCS Rizzoli Orthopedic Institute
Bologna, Bologna, 40136
Stefano Zaffagnini, 0516366075, stefano.zaffagnini@ior.it
About this study
The anterior cruciate ligament (ACL) is the primary stabilizer of the knee joint, and ACL injuries are highly prevalent, particularly among physically active and athletic individuals. Although ACL reconstruction is a well-established orthopedic procedure, significant challenges remain regarding biological integration between the graft and bone, which may negatively affect clinical outcomes.
In recent years, advanced biomaterials and regenerative medicine approaches have gained increasing attention as potential strategies to enhance osteointegration and promote more physiological tissue healing. Before clinical application, these materials must undergo rigorous in vitro biological evaluation in accordance with international standards, particularly ISO 10993-5 for cytotoxicity assessment.
Read more
The study will investigate cytotoxicity, cell viability, inflammatory responses, pro-fibrotic effects, and osteogenic potential using relevant human cell models. The regenerative effects of platelet-rich plasma (PRP), a source of growth factors, will also be evaluated.
The biomaterials under investigation include a titanium alloy and polylactic acid (PLA), both widely used in orthopedic applications. The main objective is to demonstrate their biocompatibility, absence of cytotoxic, inflammatory, and pro-fibrotic effects, and their ability to support osteogenic processes and tissue integration. The findings will provide essential evidence for subsequent preclinical in vivo studies and future clinical translation.
- Conditions
- Cytotoxicity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| PTG | Subjects eligible among patients scheduled for primary total knee arthroplasty, in whom harvesting of the tibial plateau and/or femoral condyles and/or synovial tissue is planned | |
| BMC | Concentrated bone marrow samples | |
| PRP | Platelet-rich plasma samples |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cellular health parameters
Cellular health parameters were assessed after 72 hours of exposure to the materials and compared with standardized control samples
Measured: 72 hours
Secondary outcomes (3)
Pro-inflammatory cytokines
Levels of pro-inflammatory cytokines were measured after 6, 24 and 48 hours of exposure to the materials
Measured: 48 hours
ROS
Markers of oxidative stress were evaluated after 72 hours of exposure to the materials
Measured: 48 hours
Osteogenic potential
Osteogenic potential was assessed by evaluating the gene expression of specific osteogenic markers and the production of protein biomarkers (ALP and P1NP) at 7, 14, and 28 days
Measured: 28 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Jun 2026
- Study startSep 2026 (estimated)
- Primary completionJun 2028 (estimated)
- Study completionJun 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for CytotoxicityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 50 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stefano Zaffagnini
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Stefano Zaffagnini, Istituto Ortopedico Rizzoli
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07671521
- Sponsor's protocol ID
- RAISE
- Acronym
- RAISE
- Status last verified
- Aug 2026
- First submitted
- 22 Jun 2026
- Last updated
- 4 Aug 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 4 Aug 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Biological Evaluation of Orthopedic Materials: An In Vitro Study Using Patient-Derived Human Samples
- ClinicalTrials.gov ID
- NCT07671521
- Acronym / sponsor ID
- RAISE / RAISE
- Conditions
- Cytotoxicity
- Study type
- Observational
- Recruitment status
- Not yet recruiting
- Enrolment
- 50 participants (estimated)
- Lead sponsor
- Stefano ZaffagniniUniversity, hospital or other
- Study start
- Sep 2026 (estimated)
- Primary completion
- Jun 2028 (estimated)
- Study completion
- Jun 2028 (estimated)
- First posted
- 26 Jun 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The anterior cruciate ligament (ACL) is the primary stabilizer of the knee joint, and ACL injuries are highly prevalent, particularly among physically active and athletic individuals. Although ACL reconstruction is a well-established orthopedic procedure, significant challenges remain regarding biological integration between the graft and bone, which may negatively affect clinical outcomes.
In recent years, advanced biomaterials and regenerative medicine approaches have gained increasing attention as potential strategies to enhance osteointegration and promote more physiological tissue healing. Before clinical application, these materials must undergo rigorous in vitro biological evaluation in accordance with international standards, particularly ISO 10993-5 for cytotoxicity assessment.
The study will investigate cytotoxicity, cell viability, inflammatory responses, pro-fibrotic effects, and osteogenic potential using relevant human cell models. The regenerative effects of platelet-rich plasma (PRP), a source of growth factors, will also be evaluated.
The biomaterials under investigation include a titanium alloy and polylactic acid (PLA), both widely used in orthopedic applications. The main objective is to demonstrate their biocompatibility, absence of cytotoxic, inflammatory, and pro-fibrotic effects, and their ability to support osteogenic processes and tissue integration. The findings will provide essential evidence for subsequent preclinical in vivo studies and future clinical translation.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| PTG | – | –Subjects eligible among patients scheduled for primary total knee arthroplasty, in whom harvesting of the tibial plateau and/or femoral condyles and/or synovial tissue is planned |
| BMC | – | –Concentrated bone marrow samples |
| PRP | – | –Platelet-rich plasma samples |
Who may qualify
- Ages
- 18 to 80 years
- Sex
- All
- Age groups
- Adult, Older adult
- Study population
- Subjects will be recruited among patients admitted to the IRCCS Istituto Ortopedico Rizzoli and scheduled for total knee arthroplasty for the treatment of chondral defects and/or undergoing regenerative infiltrative therapies with BMC and PRP. For the study, biological material obtained during the surgical removal of femoral condyles, tibial plateaus and synovial membranes, as well as during implantation of the prosthetic components, will be used. For BMC and PRP, only waste material not required for the surgical procedures will be collected. The recovery of such material will be performed during routine clinical practice by the medical staff of the Orthopaedic and Trauma Clinic II.
Key inclusion criteria (3 listed)
- Age 18-80 years, male or female Primary tricompartmental osteoarthritis Body Mass Index (BMI) < 35 Kellgren-Lawrence grade III-IV osteoarthritis Written informed consent
- Age 18-70 years Medial compartment knee osteoarthritis (Kellgren-Lawrence grade II-III for >4 months) Failure of ≥6 months of conservative treatment (NSAIDs/analgesics, hyaluronic acid, corticosteroid or PRP injections) Written informed consent
- Age 18-65 years Clinical signs and symptoms of knee cartilage degeneration Radiographic or MRI evidence of degeneration (Kellgren-Lawrence grade II-IV) Hemoglobin > 11 g/dL Platelet count > 150,000/mm³ No clinically relevant ECG abnormalities Written informed consent
Key exclusion criteria (5 listed)
- Previous partial knee arthroplasty or cartilage repair/regenerative procedures Rheumatoid arthritis or chronic corticosteroid/immunosuppressive therapy Positive testing for HIV, HBV or HCV infection Concentrated bone marrow (BMC) samples
- Patients of both sexes providing written informed consent and presenting with the following characteristics:
- Inability to provide informed consent Knee trauma within the previous 6 months Malignancy, rheumatic disease, uncontrolled diabetes, uncontrolled thyroid disorders Alcohol or drug abuse BMI > 35 Intra-articular injections within the previous 6 months Knee surgery within the previous 12 months HIV, HBV or HCV positivity Platelet-rich plasma (PRP) samples
- Patients of both sexes with degenerative cartilage disease of the knee.
- Rheumatoid arthritis or chronic corticosteroid/immunosuppressive therapy Uncontrolled diabetes Hematological disorders or anticoagulant/antiplatelet therapy Thyroid metabolic disorders Alcohol, drug or medication abuse NSAID use within 3 days prior to blood draw Cardiovascular disease contraindicating a 150 mL blood draw HIV, HBV or HCV positivity
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Cellular health parameters
Time frame: 72 hours
Cellular health parameters were assessed after 72 hours of exposure to the materials and compared with standardized control samples
3 secondary outcomes
Pro-inflammatory cytokines
Time frame: 48 hours
ROS
Time frame: 48 hours
Osteogenic potential
Time frame: 28 days
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Aug 2026.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Cytotoxicity, run by Stefano Zaffagnini at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 3 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 4 Aug 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact stefano zaffagnini (0516366075, stefano.zaffagnini@unibo.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cellular health parameters (time frame: 72 hours). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Aug 2026.