How Smart Surface Design Can Improve Bone Healing: Insights from LIPSS on Titanium Implants
A new publication was released by the ENDOTARGET consortium, which investigates how nanoscale surface modifications on titanium implants can regulate inflammation and influence the balance between bone formation and fat cell development. This scientific work was published in March 2026 in Applied Surface Science Advances. Authors of this study are: Andrés Pazos-Pérez, María Pineiro-Ramil, Ana Alonso-Pérez, María Guillán-Fresco, Miriam López-Fagúndez, Verónica López, Carolina Viana-Giorno, Daniel Nieto, Rodolfo Gómez, and Alberto Jorge-Mora.
Why is this research topic important?
Titanium implants are a cornerstone of modern medicine. They are used in joint replacements, fracture repair, and dental implants because they are strong, durable, and generally well-tolerated by the body. However, one key challenge remains: ensuring that the implant integrates properly with surrounding bone tissue. This process, known as osseointegration, is not only influenced by bone growth but also strongly depends on the inflammatory response. A certain level of inflammation is necessary for healing, but too much or poorly regulated inflammation can lead to complications, implant failure, or the need for revision surgery. Another important factor is how stem cells (mesenchymal progenitors) behave around the implant. These cells can differentiate into osteoblasts (bone-forming cells) or adipocytes (fat cells). A healthy balance is crucial, as too much fat formation and too little bone formation can weaken the implant’s stability, especially in ageing populations or patients with conditions like osteoporosis. Although titanium has excellent properties and biocompatibility as an implant material, it is biologically inert, which limits its capacity for osseointegration. To enhance its biological performance, laser-induced periodic surface structures (LIPSS) have emerged as a promising strategy, providing nanoscale topographies that influence cell behavior. Thus, this study focuses on how LIPSS can improve the performance of titanium implants.
How was the study conducted?
The researchers set out to systematically evaluate how LIPSSs on titanium affect inflammation and cell differentiation. Using a femtosecond laser, they created highly ordered nanoscale patterns on titanium surfaces. Four different laser power settings were tested: 50 mW, 80 mW, 100 mW, and 150 mW. Each setting produced slightly different surface structures, ranging from finely ordered nanoscale patterns to more irregular and rougher surfaces. In addition, some surfaces were coated with hydroxyapatite (HA), which is a material commonly used in implants because it has chemical and structural similarity to bone mineral. To understand how these surfaces affect biology, the researchers conducted experiments using mesenchymal stem cells, which are capable of becoming either bone or fat cells. They evaluated three key aspects:
- Inflammatory response evaluation: cells, seeded onto LIPSS titanium surfaces, were exposed to bacterial components (LPS) to simulate inflammation. Gene expression analyses were done to evaluate the inflammatory response of the cells.
- Cell differentiation: It was investigated whether cells are able to properly differentiate into osteoblasts and adipocytes on the LIPSS titanium surfaces and in what proportion, by evaluating the expression of characteristic marker genes.
This comprehensive approach allowed the team to link surface design directly to biological outcomes, something that had not been systematically done before.
What does the results show us?
The results of the study reveal a clear and fascinating pattern: not all surface modifications are equally beneficial.
- Low-power LIPSS surfaces attenuate inflammation
Overall, LPS stimulation induced a strong inflammatory response on all surfaces, but the magnitude of this response was reduced on the laser- treated surfaces compared to untreated titanium. Notably, the lower-power conditions (50 and 80 mW) showed the greatest attenuation of inflammation, meaning that low-power LIPSS lowered the expression of inflammatory genes. Interestingly, the 50 mW condition showed the clearest modulation, attenuating the expression of several inflammatory markers without abolishing acute signaling. It is important to note that a certain degree of inflammation is necessary for proper bone formation and repair.
- Low-power LIPSS surfaces promote bone formation and limit fat cell development
The osteogenic differentiation assay showed the most consistent increase in osteogenic differentiation over time in cells cultured on the 50 and 80 mV surfaces. This suggests that the nanoscale structure created by low-power LIPSS promotes osteoblast formation. At the same time, the 50 mV condition showed reduced expression of all adipogenic markers, promoting the suggestion that fat cell formation is inhibited by low-power LIPSS. This dual effect, promoting bone formation while limiting fat formation, may be particularly valuable in clinical contexts of compromised bone quality, such as aging, osteoporosis, or obesity, where an imbalance between bone-forming and fat-storing lineages undermines regenerative capacity.
- High-power LIPSS can have negative effects
As laser power increased, the results became less favourable: Inflammation levels increased, bone formation became less consistent, and fat cell differentiation increased. This suggests that more aggressive surface modification does not necessarily lead to better outcomes.
- Hydroxyapatite did not improve performance
Interestingly, adding HA did not significantly enhance results. In some cases, it even slightly increased inflammatory responses without improving bone formation. However, these results should be carefully interpreted as preliminary biological data obtained from surfaces that have only been partially characterized.
What can we learn from the study?
This research underscores a fundamental principle: small-scale design modifications can exert substantial biological effects. Across all tested power levels, LIPSS generation was successful. However, the surfaces produced elicited markedly different biological responses. The 50 mW setting maintained a well-ordered surface structure and showed the most favorable profile, including (i) reduced inflammatory activation, (ii) increased osteogenic differentiation, and (iii) diminished adipogenic commitment. This positions low-power LIPSS as a promising approach for optimising implants. Collectively, these results establish a mechanistic relationship between laser power, surface topography, and functional outcomes observed in vitro. These findings lay the groundwork for subsequent in vivo validation and translational research designed to enhance osseointegration and long-term implant performance across diverse clinical contexts.
Read the full article here: Regulation of inflammation and osteogenic–adipogenic balance on titanium surfaces: a systematic evaluation of LIPSS
Glossary
Adipocytes: are specialised cells that store fat and help regulate energy balance and metabolism in the body.
Adipogenesis: the process by which stem cells develop into fat cells.
Cell differentiation: is the process by which an unspecialised (stem) cell develops into a specific type of cell with a distinct structure and function.
Femtosecond laser: is a type of laser that emits extremely short pulses of light (lasting one quadrillionth of a second), allowing highly precise material processing without causing significant heat damage.
Gene expression: the process by which the information in a gene is used to produce a functional product, such as a protein, that carries out specific functions in the cell.
Inflammation: the body’s natural response to injury or infection, which can support healing but may become harmful if excessive or chronic.
Laser-Induced Periodic Surface Structures (LIPSS): regular nanoscale patterns created on material surfaces using laser technology to influence cell behaviour.
Lipopolysaccharides (LPS): are molecules found in the outer membrane of certain bacteria that can strongly trigger an immune response and is often used in research to simulate inflammation.
Mesenchymal Progenitors: are immature cells that can develop into different types of connective tissue cells, such as bone, cartilage, or fat cells.
Mesenchymal Stem Cells: special cells that can develop into different types of tissue, including bone, cartilage, and fat.
Osseointegration: the process by which an implant becomes firmly anchored to bone.
Osteoblasts: are specialised cells responsible for forming new bone by producing and mineralising the bone matrix.
Osteogenesis: the formation of new bone tissue.
Surface Topography: the microscopic structure and pattern of a surface, which can affect how cells interact with it.
