Biomaterials

A biomaterial is a material designed to take a form that can direct, through interactions with living systems, the course of a therapeutic or diagnostic procedure. The field spans metals, ceramics, polymers, and composites used in implants, sutures, drug-delivery systems, and scaffolds, and its ambition has shifted from materials the body merely tolerates to materials that actively direct tissue repair.

Definition and scope

Two definitions anchor the field. Biocompatibility was defined by David F. Williams in 1986 as "the ability of a material to perform with an appropriate host response in a specific application," a wording the FDA glossary still mirrors and that a 2018 review confirmed as still correct^{2 • 1}. The 2018 redefinition of biomaterial itself, by Zhang and Williams, widened the term from passive implant substances to any material that directs a therapeutic or diagnostic procedure through interaction with living systems¹.

Biocompatibility and bioactivity are different properties. Biocompatibility is the host-response requirement: the material must not provoke an inappropriate reaction in its intended site. Bioactivity is a positive capability; in bioactive glasses, it can involve bonding to living tissue through a reaction sequence beginning with rapid Na+/H+ ion exchange and formation of a silica gel layer that nucleates hydroxyl-carbonate apatite⁷. A material can be biocompatible without being bioactive, as titanium is³. The scope of the field now includes biocompatibility, bioactivity, bioderived materials, and biological tissues, with intended performance shifted from passive acceptance to an active, instructive role⁸.

History and generations

The field grew through the 1960s and 1970s, when a first generation of materials was specially developed for use inside the human body⁷. By 1980 there were more than 50 implanted prostheses in clinical use made from 40 different materials, and more than three million prosthetic parts were being implanted worldwide each year⁷.

First generation materials aimed to match the physical properties of the replaced tissue with minimal toxic host response. Most were single-phase and biologically "inert," and the interface between tissue and a bioinert implant is a thin, acellular fibrous capsule with minimal adhesion⁷.

Second generation materials were bioactive or resorbable. The mechanism of bonding of bioactive glasses of the Na2O–CaO–P2O5–SiO2 system to living tissue, established in 1971 by Hench and colleagues, involves a sequence of 11 reaction steps beginning with rapid Na+/H+ ion exchange and formation of a silica gel layer that nucleates hydroxyl-carbonate apatite⁷. The first composition, 45S5 Bioglass, has been in clinical use since 1985⁴. On the resorbable side, clinical use of poly(lactic)/poly(glycolic) acid copolymer sutures was routine by 1984, with hydrolytic decomposition ultimately yielding CO2 and H2O⁷.

Third generation biomaterials are designed to stimulate specific cellular responses at the level of molecular biology, with the bioactive and resorbable concepts converging to activate genes that stimulate tissue regeneration⁷. Third-generation materials derive from the bioactive-glass lineage⁴.

Classes of biomaterials

By structure, biomaterials divide into natural materials, metals, ceramics, polymers, and composites; by behavior, into bioinert, bioactive, and bioresorbable categories. Bioresorbable materials can be resorbed by hydrolytic breakdown and slowly replaced by advancing tissue such as bone³.

Metals offer high elastic modulus and tensile strength for load-bearing hard-tissue applications, but corrosion and stress shielding are major concerns³. Titanium, alumina, and zirconia are the standard bioinert examples³.

Ceramics are chosen for hardness and bioactivity⁹. Hydroxyapatite (HAp) and β-tricalcium phosphate are bioactive but unsuitable for load-bearing applications because of brittleness and low fracture toughness¹⁰. HAp is biodegradable but lacks the compressive strength for load-bearing use; adding titanium to HAp provides the necessary strength while adding bioactivity³.

Polymers are chosen for flexibility and ease of manipulation⁹. PEEK (polyetheretherketone) has an elastic modulus comparable to natural bone, effectively avoiding stress shielding, and is used in implant applications in orthopedics, cardiac and maxillofacial surgery, and cranioplasty¹¹.

Composites combine classes to offset individual weaknesses. Bill Bonfield's group began in the 1980s designing biocomposites matching bone's mechanical properties, leading to Hapex, a polyethylene matrix with dispersed hydroxyapatite particles, the first successful biocomposite developed for medical devices⁷.

In a head-to-head in vitro comparison of titanium alloy, zirconia, PEEK, and CFR-PEEK, zirconia had the highest nano hardness and elastic modulus, followed by titanium, CFR-PEEK, and PEEK; osteogenic markers at Day 7 were higher for titanium and zirconia than for the PEEK types, and zirconia showed the highest osteogenic gene expression at Day 14¹¹.

How the body responds

Implanted biomaterials elicit characteristic healing responses, foreign body reactions, and fibrous encapsulation, which are evaluated in vivo for devices and prostheses¹². For a bioinert implant the outcome is a thin, acellular fibrous capsule with minimal adhesion⁷. A bioactive surface instead directs mineral formation and tissue bonding, and a resorbable one is progressively replaced.

As the FDA defines it, degradation occurs when a device breaks down—perhaps by producing new chemical substances or by taking up the material—so that its mechanical or physical properties deteriorate as time passes². The fates differ by chemistry. Poly(lactic)/poly(glycolic) acid copolymers hydrolyze, ultimately yielding CO2 and H2O⁷. Magnesium is a desirable candidate for biodegradable implants, but its fast corrosion can cause implant failure before bone heals; polymer or ceramic reinforcements can control the degradation rate³.

Testing and regulation

ISO 10993-1:2025 is the current edition of the standard for evaluating how materials and components of a medical device interact with biological tissues, applied within a risk-management process and considering both composition and exposure duration⁶. The series, now numbering about 20 parts, concentrates on toxicity surrogates including cytotoxicity, systemic toxicity, genotoxicity, reproductive toxicity, and toxicokinetics of degradation products¹.

The FDA's ISO 10993-1 guidance, announced June 16, 2016, covers sterile and non-sterile devices in direct or indirect body contact and endorses risk assessments for biocompatibility evaluations¹³. FDA's assessment factors are the nature of contact (which tissues), the type of contact (direct or indirect), the frequency and duration of contact, and the device materials¹⁴. Contact duration is categorized as limited (less than or equal to 24 hours), prolonged (greater than 24 hours to 30 days), and long term or permanent (more than 30 days)¹⁴; under 21 CFR 860.3 an implant is a device intended to remain implanted continuously for 30 days or more².

FDA evaluates the final finished device, including sterilization and residuals, rather than clearing individual materials, and for absorbable or in situ polymerizing materials recommends biocompatibility evaluation at time points across polymerization and degradation so that starting, intermediate, and final degradation products are assessed¹³. Reproductive and developmental toxicity must be addressed for novel materials, materials with known reproductive or developmental toxicity, and devices with relevant target populations such as pregnant women¹⁴. In Europe, notified-body capacity is a bottleneck: only 4,873 EU MDR certificates were issued versus 14,539 applications in 2023¹⁵.

By the numbers

The global biomaterials market was valued at USD 45.15 billion in 2024 and USD 48.36 billion in 2025, projected to reach USD 68.93 billion by 2030 at a 7.3% CAGR⁵. Orthopedics claimed the largest application share in 2024, and Asia-Pacific is the fastest-growing regional segment at a 7.8% CAGR⁵.

Market reports differ on which material class leads the market. Grand View Research reports metals held the largest share, 40.56% in 2025, attributed to their mechanical properties, biocompatibility, and corrosion resistance for load-bearing implants¹⁶. Mordor Intelligence reports polymeric materials led with 39.62% of market share in 2025, with natural biomaterials projected to grow fastest at a 14.52% CAGR to 2031¹⁵. The two reports also differ on growth rates: MarketsandMarkets gives an overall 7.3% CAGR with metallics highest at 7.6%⁵, while Mordor gives tissue engineering and regenerative medicine the highest CAGR at 14.86% and Asia-Pacific 15.03% to 2031¹⁵. These are commercial market-research estimates with differing segment definitions, and the discrepancy is unresolved.

The clinical base is large. Tens of millions of individuals have had their quality of life enhanced for up to 25 years or more by implants made from bioinert biomaterials⁷.

Failures and unresolved problems

Wear debris. Bulk polyethylene is mostly inert from a host-response standpoint, but its wear debris is reactive in vivo and can generate a macrophage-mediated response leading to bone resorption¹⁷. That resorption has caused periprosthetic fracture, implant loosening, subsidence, pelvic discontinuity, and other catastrophic bone-loss complications, and early host reactions were mistakenly labeled "cement disease"¹⁷.

Nanoparticle immune failure. Metal-on-metal hip prostheses introduced in the early 2000s failed partly because their wear particles were substantially sub-micron, often 10 to 100 nm, small enough to be internalized within lymphocytes, giving in susceptible patients an idiosyncratic immune response and rapid-onset device failure¹.

Infection. Bacterial adhesion differs by surface: in the comparative study, titanium had the greatest number of adherent bacterial colonies, followed by zirconia, CFR-PEEK, and PEEK, so PEEK-type polymers show better anti-adhesion behavior¹¹.

The foreign-body capsule. The thin, acellular fibrous capsule with minimal adhesion is the interface that forms between tissue and a bioinert implant⁷.

How it compares with alternatives

Tissue-engineering scaffolds should have stiffness favoring mechanical signaling, cell-adhesive surfaces, appropriate degradation kinetics, and be non-cytotoxic, non-immunogenic, and minimally pro-inflammatory¹. Bioprinting extends this: freeform reversible embedding of suspended hydrogels (FRESH) enabled 3D printing of complex biological structures including ear and aortic heart valve constructs, and other teams have bioprinted fibrin, gelatin, and decellularized tissue-derived extracellular matrix mixtures¹⁸. At the organoid end of the spectrum, 3D bioprinted human vascular organoid sheets promoted functional ischemic repair and showed adaptive in vivo remodeling in a murine hindlimb ischemia model, evaluated with single-cell RNA sequencing¹⁹.

Recent developments

Smart materials. Stimuli-responsive "smart" biomaterials that undergo large, abrupt changes in shape in response to small changes in temperature, pH, mechanical forces, light, magnetic fields, or enzymes are increasingly used clinically, including shape memory polymers, stimuli-responsive hydrogels, and liquid crystal elastomers in embolic and hemostatic devices, orthopedics, wound healing, drug delivery, neural scaffolds, and infection control²⁰. The signals they respond to include endogenous in vivo signals and externally applied signals controlled by clinicians or patients²⁰.

Force-responsive and immunomodulatory designs. Force-responsive biomaterials can drive tissue repair by harnessing endogenous growth factors, with functional tissue response used as a potency-based quality read-out consistent with FDA and European Medicines Agency guidance for advanced cell and gene therapy products²¹. A digital light processing (DLP) bioprinted bilayer scaffold of methacrylated recombinant type I collagen carrying keratinocytes and fibroblasts accelerated diabetic wound closure, reduced ROS accumulation, induced M2 macrophage polarization, and enhanced angiogenesis and vascular maturation²².

Bioprinted vascularized constructs. Researchers have fabricated bioprinted composite soft-tissue flaps with spatially organized muscle and adipose compartments interconnected by a printed arteriovenous loop directly anastomosed to host circulation, enabling immediate perfusion upon implantation, with lymphatic vasculature incorporated in the adipose compartment to support interstitial fluid drainage²³.

Regulatory status of new printed materials. Acellular 3D printed soft-tissue scaffolds intended for implantation may be regulated as Class II or Class III medical devices through pre-market approval or 510(k) pathways, with documentation required under FDA 21 CFR 820 GMP rules and ISO 13485²⁴. GelMA (gelatin methacrylate) and its photoinitiator have not been used in any FDA-approved products, so approval would require additional biological evaluation, chemical characterization, degradation and sterilization testing, and long-term in vivo studies under the ISO 10993 family²⁴.

References

1. Specifications for Innovative, Enabling Biomaterials Based on the Principles of Biocompatibility Mechanisms, Frontiers in Bioengineering and Biotechnology (2019)
2. Glossary of Biocompatibility Terms, FDA
3. Trends in Metal-Based Composite Biomaterials for Hard Tissue Applications, JOM, Springer
4. Bioactive glass: a potential next generation biomaterial, LWW
5. Biomaterials Market Report 2025-2030, MarketsandMarkets
6. ISO 10993-1:2025, Biological evaluation of medical devices, Part 1, ISO
7. Twenty-first century challenges for biomaterials, Royal Society (PMC)
8. Biomaterials evolution: from inert to instructive, Biomaterials Science, RSC (2023)
9. Biomaterials and Chemistry, ACS book chapter (2024)
10. Biomaterials for bone tissue engineering, Biomedical Materials, IOPscience (2024)
11. In vitro physicochemical and biological properties of titanium alloy, zirconia, PEEK, and CFR-PEEK, Frontiers in Materials (2022)
12. Biological Responses to Materials, Annual Review of Materials Science
13. Use of International Standard ISO 10993-1, Federal Register (June 16, 2016)
14. Biocompatibility Evaluation Endpoints by Device Category, FDA
15. Biomaterials Market Size, Forecast, Analysis & Share 2031, Mordor Intelligence
16. Biomaterials Market Size & Share, Industry Report 2033, Grand View Research
17. Orthopedic Implant Materials, StatPearls, NCBI Bookshelf
18. Three-dimensional printing of complex biological structures by FRESH, Science Advances
19. 3D bioprinted human vascular organoid sheets, BMC Medicine, Springer
20. Smart Polymeric Biomaterials for Clinical Use, Annual Review of Biomedical Engineering
21. Force-responsive biomaterials drive tissue repair, Nature Materials
22. DLP Bioprinting of Bilayer Recombinant Collagen Scaffolds, ACS Applied Bio Materials
23. Bioprinted vascularized soft-tissue flaps with an integrated arterial-venous loop, Cell Biomaterials
24. Large-scale manufacturing of precisely patterned flexible soft tissue implants, Biofabrication, IOPscience

Topic: Encyclopedia › Technology and the built world › Engineering and manufacturing › Chemical, biochemical, and biomedical engineering › Titles A to Mi

Initially written Sep 17, 2026 · Reviewed: Sep 17, 2026; Sep 30, 2026; Oct 15, 2026 · Edited: Sep 30, 2026; Oct 15, 2026; Oct 21, 2026; Oct 25, 2026 · Last review: Oct 15, 2026

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