Bone Implantation Biocompatibility Testing (ISO 10993-6)
1. Biological Effect: In Vivo Tests
2. Turnaround time: 12 or 21 weeks or more (after approval from Local Ethics Committee)
3. Sample Requirements:
ISO
to be individually determined;
4. Animal Quantity: 10 or 5 or 3 rabbits (depending on the number of implantation sites)
5. Duration of implantation: 4 weeks or 13 weeks or to be individually determined
ISO 10993-6
The purpose of the study is to evaluate the medical device for local effects on living tissue when implanted in rabbit femurs. Test item is implanted at the distal, medial, and proximal locations of the femur. The bioreactivity of a test item is determined through microscopic and macroscopic comparison of the tissue response caused by the medical device as compared to an appropriate control material. The area of the tissue surrounding the center position of each implant will be processed and a histopathologist will process the implanted sites for histopathological evaluation.
What is Bone Implantation Testing?
Bone implantation testing is a biocompatibility study described in ISO 10993-6 standard for local effects after implantation. It evaluates how bone tissue responds when a medical device material is implanted, measuring healing, inflammation, and integration with the surrounding bone.
Purpose in regulatory submissions
Regulators such as the FDA and European authorities under MDR require bone implantation studies for many devices intended to contact bone. The data help demonstrate that a material is safe, well-tolerated, and capable of supporting long-term function.
For example, the FDA guidance on modified metallic orthopedic implants outlines expectations for evaluating materials that directly interface with bone or bone cement. Without this kind of evidence, a submission cannot move forward.
Why is bone tissue chosen
Bone is not just structural but dynamic. It remodels continuously, responds to mechanical stress, and has a rich blood supply. These features create a challenging yet accurate environment for testing how implants perform under real physiological conditions.
A device that integrates well into bone, resisting resorption or fibrous encapsulation, is far more likely to succeed in clinical use.
Differences from muscle implantation tests
Muscle implantation tests focus on how soft tissue responds:
- Inflammation
- Fibrosis
- Necrosis
Bone implantation adds another dimension: osseointegration. Researchers look not only for the absence of harm but also for evidence that new bone can form around and anchor the implant.
This makes bone testing critical for orthopedic, dental, and other load-bearing devices where mechanical stability is just as important as biocompatibility.
Bone implantation is a required part of the biocompatibility testing for the bone implants process, ensuring materials can integrate safely with living tissue.
Key Regulatory Standards and Guidance
The foundation for bone implantation testing is the ISO 10993-6:2016 standard for local effects after implantation. It describes how to evaluate the tissue response when a material or device is placed into a living bone.
This standard is recognized worldwide and is used by regulators as part of medical device submissions. It sets out:
- how long should studies run
- how samples are implanted
- how tissues are analyzed (both with the naked eye and under the microscope)
By following ISO 10993-6, labs like NABI can generate results that regulators trust and manufacturers can use in FDA and MDR submissions.
FDA guidance on orthopedic implants
In the United States, the FDA guidance on modified metallic orthopedic implants provides detailed expectations for devices that contact bone or bone cement. It explains the types of data required to show that a material is safe and effective for orthopedic use, especially when metallic surfaces are modified or coated.
Successful submissions often depend on aligning biocompatibility strategy with both FDA and MDR requirements to satisfy international expectations and avoid regulatory delays.
FDA draft guidance for metallic & calcium phosphate coatings
Some devices use special coatings to improve how they interact with bone. These coatings can:
- change surface chemistry
- influence bone bonding
- affect long-term stability
The FDA draft guidance for metallic & calcium phosphate coatings explains how manufacturers should characterize and test these surfaces before approval.
This guidance is especially relevant for orthopedic implants with porous or coated surfaces, where the coating is expected to encourage bone ingrowth.
Proper characterization helps regulators understand how the device will perform once implanted and reduces the risk of unexpected failures in patients.
Other regulatory references and literature
In addition to ISO and FDA documents, there are other resources that provide deeper insight into bone implantation testing and evaluation.
- A peer-reviewed article in Frontiers in Bioengineering and Biotechnology explores new approaches to biocompatibility testing for implants and highlights novel tools for improving safety assessment.
- Industry experts have also published a practical guide to ISO 10993-6 implant effects, which explains how to interpret tissue reactions and what regulators look for in submissions.
These references complement regulatory guidance by showing how standards are applied in practice and where research continues to refine testing methods.
How Long Do Bone Implants Last in Testing?
Bone implantation studies usually last 4 weeks for sub-chronic evaluations or 13 weeks for chronic studies. The exact duration depends on the regulatory question and study design.
In a testing context, “lasting” refers only to how long the sample stays implanted before tissues are removed for analysis.
A 4-week study captures short-term reactions like inflammation and early healing. A 13-week study looks further ahead, showing bone remodeling, integration, and any delayed responses.
This is very different from clinical or cosmetic implants. Orthopedic devices (such as hip replacements or dental screws) are designed to remain in the body for many years, sometimes a lifetime.
Pre-clinical testing, by contrast, is tightly controlled and time-limited, focusing on safety and compatibility rather than permanent function. Careful planning of the Biological Evaluation Plan can help fast-track market approval while keeping testing timelines under control.
What Outcomes Are Measured in Bone Implantation?
Bone implantation studies measure outcomes such as osseointegration, bone resorption, necrosis, fibrosis, inflammation, and biomechanical stability.
- Osseointegration – The direct attachment of bone to the implant surface. This is the ideal outcome, showing that the device can anchor securely. It’s evaluated through histology, looking for new bone formation around the implant.
- Bone resorption – The breakdown or loss of bone around the implant. This can weaken stability and signal poor compatibility. Histology and imaging reveal whether bone density is being lost.
- Necrosis – Dead bone tissue near the implant. It may appear as empty spaces or damaged cells under the microscope. Necrosis is a red flag that the material isn’t tolerated.
- Fibrosis – Formation of scar-like tissue instead of bone. It suggests the body is walling off the implant rather than integrating with it. Fibrosis is assessed microscopically, often alongside capsule thickness.
- Inflammation – The immune system’s reaction to the implant. Acute inflammation shows up quickly, while chronic inflammation can last for weeks. Both are tracked through gross observation and histology.
- Biomechanical stability – The ability of the implant to stay fixed under stress. In some studies, mechanical testing checks whether the implant holds firm or loosens under force.
Together, these outcomes provide a complete picture of safety and performance. Regulators expect not only the absence of harm but also evidence that a device can remain stable and functional in bone.
Which Devices Are Candidates for Bone Implantation Testing?
Typical candidates for bone implantation tests include metals, ceramics, composites, and surface coatings that will contact bone.
Manufacturers usually need this data at the preclinical stage to support regulatory submissions. Testing may also be required when devices are modified, for example, a new coating on an orthopedic screw or a change in alloy composition for a dental implant.
Bone implantation testing is most often applied to:
- Orthopedic devices such as plates, screws, or joint replacements
- Dental implants that rely on osseointegration
- Coated or surface-modified devices where bone contact is expected
By evaluating tissue response early, manufacturers reduce the risk of costly delays in FDA or MDR reviews.
How Much Does Bone Implantation Testing Cost?
The cost of bone implantation testing varies based on study design. There is no flat price, since factors like duration, number of animals, and analysis requirements all influence the budget.
Several elements shape the final cost:
- Number of implantation sites – more sites require more animals and more analysis.
- Study duration – 4-week studies are shorter and less resource-intensive than 13-week chronic studies.
- Histology complexity – detailed microscopic analysis adds time and cost.
- Sample preparation – sterilization, sizing, and labeling may be needed before testing.
- Ethical approvals – timelines and administrative steps vary by project.
- Additional analyses – imaging or biomechanical testing can increase the scope and price.
Because every device is different, NABI provides tailored estimates instead of fixed costs. The overall budget is directly tied to project design, and this includes details like how many samples are needed for biocompatibility tests.
Request a custom quote from NABI to receive an exact cost for your study.
Why Choose NABI for Bone Implantation Testing?
Choosing a lab partner is about trust, compliance, and confidence that your data will stand up to regulatory review. NABI was built with that mission in mind.
- Accreditations you can rely on. Our work follows ISO 10993, GLP principles, and ISO 17025 accreditation. Every dataset aligns with global regulatory expectations.
- Expertise in complex testing. With decades of combined experience in biocompatibility and toxicology, our team is skilled in managing bone-specific challenges like osseointegration and remodeling.
- Ethics and transparency. All studies undergo Local Ethics Committee approval. Animal welfare is integrated into our protocols from the start.
- Efficiency without compromise. Typical projects are completed within 12–21 weeks, with custom-tailored study designs to fit your device and regulatory pathway.
- Clear, regulator-ready deliverables. Clients receive full reports, including histopathology images, gross observations, and contextual interpretation, not just raw data.
Bone implantation is one of the most demanding areas of biocompatibility testing. By working with NABI, you gain not only data but also the confidence that comes from a partner committed to science, compliance, and responsible innovation.
FAQs about Bone Implantation Biocompatibility Testing
What animals are used for bone implantation?
Bone implantation studies are usually performed in rabbits, with implants placed in the femur. Rabbits are widely accepted because their bone structure allows for consistent evaluation of tissue response.
What regulatory agencies accept ISO 10993-6 / bone implantation test data?
The FDA accepts results from ISO 10993-6:2016 studies, the European Medicines Agency (EMA) under MDR, and other global authorities that follow ISO standards.
How are bone responses evaluated (gross vs microscopic vs imaging)?
Evaluation is done at several levels:
- Gross observation of the implant site for visible changes
- Microscopic histology to detect osseointegration, necrosis, fibrosis, or inflammation
- Imaging and mechanical testing when stability and bone density need to be assessed
How many animals/samples are needed for typical studies?
The number depends on the study design and regulatory requirements. Most protocols use several animals with multiple implant sites to allow comparison between test and control materials.
Can the study timeline be shortened?
Timelines can sometimes be shortened if ethical approvals and samples are ready in advance. However, 13-week chronic studies cannot be compressed, since regulators require the full duration.
What is the difference between bone implantation testing and orthopedic load-bearing implant evaluations?
Bone implantation testing focuses on local tissue response: how bone reacts to a material in a controlled setting. Orthopedic load-bearing evaluations also test mechanical performance, checking whether the device can withstand real-life stresses while integrating with bone.
Get a Custom Quote for Bone Implantation Testing
Every device and material is different, and so is the study design. That’s why NABI provides custom quotes instead of fixed pricing. By tailoring each project to your regulatory pathway, we make sure you receive the data regulators expect, on time and with full transparency.
For direct inquiries:
Email: contact@nabi.bio
Phone: +1 (407) 278-6815
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