Putting on a "degradable new coat" for bone defect implants

Team members are using plasma immersion ion implantation equipment
.
Photo courtesy of Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences

Group photo of team members

Bone defect is a common clinical disease

Prosthesis implantation surgery is the first choice for the treatment of large bone defects
.

At present, the artificial materials implanted in the human body mainly include metal, inorganic non-metal and organic polymer materials, while the corresponding orthopedic implant materials are specifically titanium alloy (metal) and hydroxyapatite (inorganic non-metal) , polyether ether ketone (polymer) and the like
.

Because it is a synthetic material that cannot be completely consistent with the natural bone tissue composition, all these materials will produce foreign body reactions to varying degrees when implanted in the human body, which is a self-protection effect of the human immune system
.

Recently, researchers from the Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences have constructed a degradable coating on the surface of the implant that has the function of regulating the immune-osteogenesis sequence.
Establish a solid integration between
.
The research results were published online in The Innovation

"Top-down" grooming strategy

The use of artificial implant materials for bone defect repair is a complex cascade reaction process that is affected by multiple physiological factors, including two interrelated stages of early inflammation and subsequent bone repair
.
At the same time, with the deepening of research, more and more researchers have realized the importance of immune regulation in the process of bone defect repair

However, the material surface properties required for early immune regulation are not exactly the same as the material surface properties required for subsequent osteogenic repair
.
"For this reason, we got inspiration from this, hoping to build a gradient functional coating that can slowly degrade in the physiological environment on the surface of orthopedic implant materials, and then realize the'immune-osteogenesis sequence through the sequential release of functional components during the degradation process.

In order to match the two key stages in the process of bone tissue regeneration and repair, the research team adopted a "top-down" modification strategy
.
First of all, polyetheretherketone (PEEK), a commonly used medical polymer material for orthopedic implants, is selected as the substrate, and the controllable degradation polytrimethylene carbonate (PTMC) is used as the coating material to support dexamethasone with bone-promoting function ( DEX); Later, based on the characteristic plasma immersion ion implantation (PIII) technology, the cytokine IL-10 with inflammation regulation function was grafted on the surface of the coating

After the samples were prepared, the release time sequence of DEX and IL-10 in the PEEK surface composite coating was studied
.
The results show that the cytokine IL-10 grafted on the surface of the coating can be completely released within 7 days, while the release period of DEX loaded inside the coating reaches about 30 days

In order to verify the effectiveness of the "immune-osteogenesis timing regulation" strategy, the research team conducted in vitro cell culture and animal implantation experiments.
The results further proved that the immune-osteogenesis regulation effect of the new composite coating can be better.
Match the timing process of bone defect repair
.

Traditional materials are replaced with "new clothes"

In fact, orthopedic implant materials are also popular research directions abroad, but most researches focus on tissue engineering scaffolds (3D printing, electrospinning, etc.
)
.

However, for the repair of large-scale bone defects, the mechanical properties of implant materials have high requirements, and the general bone tissue engineering scaffolds are often difficult to meet
.

Therefore, the research team focused on the surface functional modification of traditional orthopedic implant materials (medical titanium alloy, polyetheretherketone, etc.
) that have excellent mechanical properties and have been used in clinical practice, while retaining the excellent mechanical properties of the implant material itself.
Given its certain functions, the new orthopedic implant materials developed by this strategy will be closer to practical applications
.

As the first research on "Immune-osteogenesis timing regulation" on the surface of implant materials, "The significance is that it can not only bring some inspiration to other research work on orthopedic implant materials, but also comprehensively consider the immunity around implant materials— The bone formation cascade reaction process, and because our coating preparation method is relatively simple and suitable for different materials of biological materials, it is expected to provide an effective reference for the research on the surface function construction of other biological materials
.
Rejoicing

The results of the research are indeed exciting, but only those who have experienced it can experience the taste of the process
.
In the research process, the researchers also encountered many difficulties, but in the end they rely on the strength of the team to successfully tackle the tough problems
.

"The coating material we selected in the study was polytrimethylene carbonate.
However, in the subsequent in vitro simulated degradation experiments, it was found that the prepared coating degraded very slowly in phosphate buffer, and it was found in animals.
The degradation process did not match.
Later, through literature research, it was found that the degradation of polytrimethylene carbonate coating requires the participation of lipase, and we have solved this problem
.
” The first author of the research, Shenzhen Advanced Institute of Chinese Academy of Sciences Xie Lingxia, research assistant at the Institute of Technology, told China Science Daily
.

For another example, in the process of grafting cytokine IL-10 on the coating surface, Wang Huaiyu’s team hoped to avoid the use of chemical crosslinking agents as much as possible.
Later, based on the “activation” effect of gas PIII treatment on the coating surface, they finally managed to Realize the loading of biomolecules on the coating surface in a linker-free manner
.

The research and development of new orthopedic implant materials requires comprehensive consideration of the immune-osteogenesis cascade reaction process of bone defect repair.
For this reason, based on existing research, "our team will further develop the surface immunity of orthopedic implant materials.
—Research on osteogenesis timing control and further specific application scenarios, such as the design and construction of gradient functional coatings for osteoporosis patients’ bone metabolic imbalance and weak new bone generation ability
.
" Wang Huaiyu Finally said
.

Related paper information: https://doi.
org/10.
1016/j.
xinn.
2021.
100148