hyaluronic acid

The new treatment does not
alter the roughness and

it speeds up the osseointegration process

Biochemical modifications of Ti implant surfaces (BMTIS)

Partial surface treatment with hyaluronic acid on the implant body.
Cold plasma decontamination.

Biochemical methods of surface modification strive to use the current understanding of the biology and biochemistry of cellular function and differentiation. “Biochemical surface modification uses critical organic components of bone to affect tissue response”. The goal of biochemical modifications is to immobilize proteins, enzymes or peptides on devices surfaces to induce specific cell and tissue responses. Puleo da Nanci a (1999): understanding and controlling the bone-implant interface, biomaterials, 20:2311-2321.

MAG
52 X
WD
11.5 mm
EHT
20.00 kV
Signal A
CZ BSD

MAG
200 X
WD
11.0 mm
EHT
20.00 kV
Signal A
CZ BSD

MAG
1.50 K X
WD
11.5 mm
EHT
20.00 kV
Signal A
SE1

Hyaluronic acid and osseointegration

In 1904 Pfaundler hypothesized that calcium-binding was an important step during the calcification of the bone and that some unknown component of the bone was responsible; It was later discovered that GAGs play an important role and that HA enhances proliferation and growth of hydroxyapatite crystals; Iwata and Urist found that large amounts of HA were secreted when implants of decalcified bone remineralized as bone (Clin. Orthop. Rel. Res., 90, 236, 1973); In vitro studies using fetal calvarial cells and bone marrow osteogenic stem cells show that osteogenesis in vitro is significantly enhanced by HA 30-160 kDa, while high Mw HA (550-1300 kDa) shows weak inhibitory effect as compared to the control (G. W. Bernard et al. Redefining Hyaluronan, Abatangelo and Weigel Eds., Elsevier, 2000, pp. 215-231); 800 kDa HA added to bone marrow stromal cells cultured in vitro accelerates cell proliferation, increases ALP activity and osteocalcin gene expression. HA interacts with BMP-2 to generate direct and specific cellular effects (X. Zou et al. Biomaterials 25, 5375, 2004); 900 kDa HA has a positive effect on bone ingrowth in Titanium fibre mesh implant in rats (S. Itoh et al. J. Mat. Sci. Mat. Med., 12, 575, 2001); HA shows a positive effect in early bone consolidation in distraction osteogenesis (B. C. Cho et al., J. Craniofacial Surg., 13, 783, 2002).

Sa 0,50 µm

Overall mean value on a measuring area of 30×30 μm, cold plasma decontamination.

Sa 1,90 µm

Overall mean value on a measuring area of 30×30 μm, sand-blasting, double etching, cold plasma decontamination.

Hyaluronic acid and Ti implants

Ti
implant

Surface
functionalization

Amino groups rich surface Ti implant

HA (Mw 800kDa)
covalently linked

Ti implant with HA surface treatment

Results (cortical bone)

Descriptive studies:
histomorphometry (n = 5)

Evaluation of newly-formed
bone quality: microhardness of
interfacial bone (n = 5)

Functional studies:
mechanical tests (n = 10)

BIC: the length of bone directly opposed to the implant without the presence of a fibrous membrane/the total length of the bone-implant interface x 100 Bone ingrowth: bone area between the screw and the line connecting the thread crests divided by the total screw thread area x 100.

Microhardness measurements were performed in the tangential direction to the interface with a Vickers indenter (four-sided pyramid with square base and an apex angle between opposite sides of 136°±15’) applied at a load of 0.05 kgf and dwell time of 5 sec.

The push-out test was carried out by placing the femoral segments on a support jig (∅ 3.5 mm) using a MTS apparatus (Sintech-1/M, MTS Adamel Lhomargy, Ivry sur Seine, France). A force was applied to the implant from the medullar side at a constant crosshead speed of 2 mm/min, pushing it out from its bony bed.

Results (trabecular bone)

Histomorphometric results for uncoated and coated screws IN TRABECULAR BONE at 4 weeks (n=5)

Wilcoxon signed rank test: *, p<0.05; **, p<0.01

parameters
Uncoated (screw)
Coated (screw)
BIC (%)
Median
22.5
69.0**
SEM
5.8
5.8
(Min – Max)
(16.1 – 47.4)
(45.4 – 80.7)
Bone Ingrowth (%)
Median
30.3
56.3**
SEM
2.0
3.4
(Min – Max)
(23.9 – 33.9)
(41.9 – 59.4)

Conclusions

HA covalently linked to nanoporous Ti implant surfaces significantly increases bone growth at 4 weeks (histomorphometry). There’s not only more bone (histomorphometry) but interfacial bone is significantly more mature in the case of HA-coated implants (microhardness). Functional studies (push-out force) confirm the significant improvement of osteointegration at early stages. HA coating effects are magnified in the more biochemically rich (and clinically more difficult) trabecular bone. Hypotheses&mechanisms that could account for the observed results: Increased hydrophilicity of the HA-coated surface, Charge effects (Ca2+ binding, Ca2+ mediated mechanisms), Role of HA in wound healing, HA is found whenever there is the need for rapid cell proliferation, repair and regeneration. During an early stage of osteogenesis, when only undifferentiated mesenchymal cells are found, HA reaches peak levels.

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