Bioceramics, a distinct subgroup of biomaterials, have significantly transformed the medical industry through their utilisation in surgical implants, prosthetics, and regenerative medicine. These sophisticated materials, made from ceramic compounds, are specifically engineered to interact seamlessly with biological tissues.
Bioceramics are derived from ceramics, materials traditionally known for their hardness and resistance to wear. However, unlike their counterparts in pottery or construction, bioceramics are tailored for medical use. These materials include alumina, zirconia, and calcium phosphates like hydroxyapatite, which closely mimic the mineral composition of bone. Bioceramics have become a cornerstone of modern grafting techniques, offering unparalleled biocompatibility, bioactivity, and mechanical properties. From bone grafts to dental implants and joint replacements, these advanced materials are transforming the landscape of medical treatments. Biocompatibility is critical, ensuring the materials do not produce adverse reactions and support normal healing processes. Biomaterials are vital in enhancing the quality of human life and are widely used in joint replacements, artificial arteries, skin substitutes, and bone substitutes.
Bioceramics have significantly advanced over the past two decades, enhancing the repair and regeneration of calcified tissues. The increasing elderly population and related ailments drive the demand for novel biomaterials capable of replacing damaged tissues and promoting the body’s regeneration potential. Bioceramics, such as calcium phosphates, bioactive glasses, and glass ceramics, are designed to mimic the structure of native calcified tissue, playing a crucial role in tissue engineering and drug delivery.
The Bioceramics Lab at Sree Chitra Tirunal Institute for Medical Science and Technology (SCTIMST) has been at the forefront of developing Bioceramics based on calcium phosphate and calcium sulphate routes. The development of materials via indigenous routes and with adherence to quality standards that are at par or exceed international standards provides Indian citizens access to high-tech health care. The lab has been established under the leadership of Dr Harikrishna Varma PR and is currently led by Dr Manoj Komath. The research carried out in this lab has been supported by product viability in the market, which is attested to the current market trends and ongoing demand in the Indian sub-continent and abroad for synthetic bone grafts for routine applications. The lab has more than 30 patents filed, and granted, ensuring that technology development is completed within the time frame.
All Images Courtesy: Dr Francis B Fernandez and Dr Biju Dharmapalan
BIOCERAMICS AS SYNTHETIC BONE GRAFTS
Bioceramics are a notable breakthrough in bone grafting since they possess a blend of biocompatibility, bioactivity, and mechanical properties that facilitate successful bone regeneration and integration. Bone is a metabolically active tissue that contains a variety of cells interspersed in a complex system. Components of the system include extracellular matrix, which consists of collagen and a mineral phase of calcium phosphate crystals, which is primarily composed of hydroxyapatite. Due to its inherently dynamic nature, bone has the capacity to regenerate in small quantities. However, critical sized defects require bone substitutes in order to heal adequately and retain their original strength. These are inordinately acquired via high energy trauma, infections & as an aftermath of tumour excision.
Autografts have remained the ‘gold standard’ of bony reconstruction. This is met with a lack of supply and associated morbidity in practical application. In the Indian scenario, lack of access to quality banked bone also renders reconstruction painful and reliant on Ilizarov’s apparatus or other modes of distraction osteogenesis. Ideally, large-sized defects created secondary to trauma, infection or pathology ultimately require bone replacement strategies, and this may be in the form of an osteoinductive, osteoconductive or osteogenic material. Bioceramics are favoured in this application due to the following properties,
1. Biocompatibility
Bioceramics are highly biocompatible, meaning they do not induce an immune response when implanted in the body. This compatibility reduces the risk of inflammation and rejection, which is crucial for the success of bone grafts.
2. Bioactivity and Osteoconductivity
Many bioceramics, such as hydroxyapatite (HA) and tricalcium phosphate (TCP), are bioactive and osteoconductive. They support the growth of new bone by providing a scaffold that encourages the attachment and proliferation of osteoblasts, the cells responsible for bone formation. This property enhances the integration of the graft with the natural bone.
3. Osteoinductivity
Some bioceramics possess osteoinductive properties, meaning they can stimulate precursor cells to differentiate into osteoblasts. This capability is particularly significant for enhancing bone regeneration in areas with limited natural bone growth.
4. Structural Similarity to Bone
Bioceramics like hydroxyapatite closely mimic the mineral composition and structure of natural bone. This similarity promotes better integration and stability of the graft within the bone tissue.
5. Mechanical Properties
While bioceramics can be brittle, advances in material science have developed composites and engineered structures that improve their mechanical strength and toughness. This makes them suitable for load-bearing applications where mechanical stability is essential.
6. Porosity and Resorbability
Bioceramics can be engineered to have a porous structure, which facilitates vascularisation and the infiltration of bone cells. Additionally, certain bioceramics are resorbable, meaning they gradually dissolve and are replaced by natural bone over time. This resorbability helps in complete integration of the graft into the body.
7. Reduced Risk of Disease Transmission
Unlike allografts (bone grafts from a donor) or xenografts (bone grafts from another species), synthetic bioceramics eliminate the risk of disease transmission. This factor makes bioceramics a safer option for patients.
8. Customizability
Bioceramics can be easily shaped and tailored to fit specific defects or surgical requirements. Advanced manufacturing techniques, such as 3D printing, enable the creation of custom implants that perfectly match the patient’s anatomy.
STEPS INVOLVED IN THE DEVELOPMENT OF BIOCERAMICS
The development of bioceramics begins with extensive research into their chemical composition, structure, and mechanical properties. The primary goal is to create materials that mimic the natural bone environment, promoting osteoconduction (bone growth on the surface) and osteoinduction (inducing the formation of new bone). The consistent interaction with clinicians catalyses this to understand day-to-day problems that can be solved by innovation in material science.
Preclinical Testing
Before clinical use, bioceramics undergo rigorous preclinical testing to evaluate their safety, efficacy, and performance. Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST), Thiruvananthapuram, offers an accredited process for engaging in material development and validation.
- In Vitro Studies:
- In vitro tests assess cell viability, proliferation, and differentiation when in contact with bioceramics. These studies help understand the material’s cytocompatibility and its potential to support bone cell growth.
- In Vivo Studies:
- Animal models are used to study the bioceramic’s integration with bone tissue, its degradation rate, and the overall biological response. These studies provide crucial data on the material’s osteoconductive and osteoinductive properties.
- Sterilisation and Stability:
- Bioceramics must withstand sterilisation processes without losing their beneficial properties. Studies also evaluate the long-term stability of the material in the body.
INNOVATION AT SCTIMST BIOCERAMICS LABORATORY
The lab has translated technologies related to pure hydroxyapatite, silica-substituted apatite, calcium sulphate cements and drug delivery systems. In collaboration with Dr Vrisha of CMC Vellore, the lab demonstrated the first in-human application of tissue-engineered ceramic for bone reconstruction.
Regulatory Approval
The transition from preclinical studies to clinical use involves obtaining regulatory approval from agencies like the US Food and Drug Administration (FDA), European Medicines Agency (EMA) and Indian Council of Medical Research (ICMR), and Central Drugs Standard Control Organisation (CDSCO). Bioceramics must meet stringent regulatory guidelines for safety, biocompatibility, and performance. This involves extensive documentation and submission of preclinical data. At SCTIMST, about 20 biological tests, including biocompatibility testing, are accredited by Le Comité Français d’Accréditation (COFRAC) of France. The test reports of all accredited tests are issued with the COFRAC logo. SCTIMST has also received a Certificate of Registration to carry out Test of Evaluation of Medical Devices on behalf of the manufacturer under the Medical Device Rules 2017. The following medical devices can be tested or evaluated as required.
| S.No. | Generic name | Class of medical devices |
| 1 | Cardio-vascular Devices (Biological Evaluation as per ISO 10993) | Class D |
| 2 | Neuroprosthesis (Biological Evaluation as per ISO 10993) | Class D |
| 3 | Orthopedic Implants (Biological Evaluation as per ISO 10993) | Class C |
| 4 | All medical devices and Materials (Biological Evaluation as per ISO 10993) | Class D |
| 5 | Dental Implants (Biological Evaluation as per ISO 10993) | Class B |
Clinical Implementation
Upon successful regulatory approval, bioceramics are introduced into clinical practice. Human clinical trials are conducted in phases to assess the safety and efficacy of the bioceramic material in a controlled environment. These trials help identify potential adverse effects and verify the material’s performance in humans.
This stage involves collaboration between material scientists, biomedical engineers, clinicians, and surgeons.
- Orthopaedic Applications:
- Bioceramics are used in bone grafts, spinal fusion devices, and joint replacements. Their ability to integrate with bone tissue makes them ideal for these applications.
- For example, HAp coatings on titanium implants enhance osseointegration, improving the stability and longevity of the implants.
- Dental Applications:
- In dentistry, bioceramics are used for tooth root replacements, bone grafts in periodontal defects, and as coatings for dental implants. These materials promote faster and more reliable integration with the jawbone.
- Customised Implants:
- Advances in 3D printing technology allow for the customisation of bioceramic implants to match the patient’s anatomy. This personalised approach enhances the fit and function of the implants.
Bioceramics are used in bone grafts, spinal fusion devices, joint replacements, and tooth root replacements, among several other cases. As they are biocompatible, they do not induce an immune response when implanted in
human body
CHALLENGES AND FUTURE DIRECTIONS
Despite the significant progress, several challenges remain in the clinical translation of bioceramics.
- Mechanical Limitations:
- The brittleness of bioceramics can limit their use in load-bearing applications. Research is ongoing to improve their mechanical properties while maintaining bioactivity.
- Resorption Rates:
- Balancing bioceramics’ resorption rate with the new bone formation rate is crucial. Materials that resorb too quickly may not support new bone growth.
- Complex Biological Interactions:
- Understanding the complex interactions between bioceramics and the biological environment is essential for optimising their performance. This includes studying the immune response and the influence of various biological factors on material degradation and bone formation.
CONCLUSION
The clinical translation of bioceramics represents a significant achievement in biomedical engineering and materials science. Through rigorous research, testing, and collaboration, bioceramics have become vital tools in orthopaedic and dental applications, offering improved patient outcomes. As research continues to address existing challenges and explore new frontiers, the future of bioceramics in clinical practice looks promising, with the potential for even more advanced and effective treatments for bone-related conditions. Bioceramics face challenges such as brittleness and lower tensile strength, limiting their use in load-bearing applications. Advanced processing techniques are necessary to achieve desired properties, which can be complex and costly. Continuous advancements in material science and technology are essential to overcome existing challenges and expand the applications of bioceramics in biomedical engineering.
The Bioceramics Laboratory at the Biomedical Technology Wing, SCTIMST has translated technologies related to pure hydroxyapatite, silica-substituted apatite, calcium sulphate cements and drug delivery systems. The lab has been at the forefront of maintaining the cutting edge in ceramic technologies for life-saving applications in India. The technologies translated from the SCTIMST will benefit the patients not only in the country but globally, making Indian healthcare products acceptable globally.
Sree Chitra Tirunal Institute for Medical Sciences and Technology (SCTIMST) is an Institution of National Importance in India established in 1976 in Thiruvananthapuram, Kerala. The institute is a statutory body under the Ministry of Science and Technology and is under the administrative control of the Department of Science and Technology, Government of India. It has three wings: a tertiary referral super speciality hospital, a biomedical technology wing and the Achutha Menon Centre for Health Science Studies. The Institute focuses on high-quality, advanced treatment of cardiac and neurological disorders, indigenous development of biomedical devices and materials technologies, and public health training and research. The institute has excellent facilities and teams of professionals dedicated to developing innovative biomedical devices and products, evaluating medical devices to global specifications, training in novel medical specialities, and conducting research in medical and public health areas of social relevance. The institute is a Technical Research Centre for Biomedical Devices and has a medical devices incubator (TIMed). The institute has the status of a university and offers postdoctoral, doctoral and postgraduate courses in medical specialties, public health, nursing, physiotherapy, basic sciences and healthcare technology. More about the institute is available on the website, https://www.sctimst.ac.in/
Dr Francis B Fernandez is Scientist–D, Department of Biomaterial Science and Technology, Sree Chitra Tirunal Institute for Medical Science and Technology, Thiruvananthapuram. He can be reached at francisbf@sctimst.ac.in; Dr. Biju Dharmapalan is a science communicator and an adjunct faculty at the National Institute of Advanced Studies, Bangalore. He can be reached at bijudharmapalan@gmail.com.
