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The Preformed Spacers: From The Idea To The Realization Of An Industrial Device

Renzo Soffiatti, PhD
Tecres, S.p.A.

At the beginning of the 1990s, when visiting hospital operating rooms, it was possible to see surgeons modelling bone cement with their hands to obtain handmade devices with a prosthesis- like geometry. The device was created to temporarily replace removed septic prosthesis. The positioning in the septic site of an antibiotic bone cement device aimed to strengthen the systemic antibiotic therapy. Systemic antibiotic therapy is not always able to guarantee optimal antibiotic concentration in the infected site. Some months after implantation, the device was removed and replaced with a new prosthesis, giving back to the patient a healed joint and a certain functional recovery. This device was called a “spacer.”1,7,13,14

MECHANICAL FAILURE

Unfortunately, in many cases, it was possible to see bad situations, determined by mechanical failure of the hand made devices. Although breakage was a feared and undesired complication, surgeons were very satisfied with the antiseptic effectiveness of the device. In other words, the spacer and the systemic treatment increased the probability of infection healing compared to systemic antibiotic therapy alone.

SPACER-G

These positive results led Tecres to systematically research and study spacers made by the surgeon, and design a device that could be mechanically safe and pharmacologically effective at the same time. In other words, a “reproducible effective device” and a device that could also give the patient a better quality of life.

With these key features, the Spacer-G was designed (Figure 1). Its geometry was studied to permit an optimal interaction between the acetabulum and the femur. The anatomical stem-neck angle was chosen to limit dislocation as much as possible, the saddle shaped neck was designed to limit the possible acetabular protrusion and the extreme smoothness of the head meant to reduce the possible generation of debris.

Figure 1. Spacer-S, shoulder spacer; Spacer-G, hip spacer; Spacer-K, knee spacer

 

An inner stainless steel bar (Figure 2) was inserted to provide high mechanical strength and gentamicin was chosen as the antibiotic due to the wide spectrum of activity and the good properties of release from PMMA.

Figure 2. Inner core present in Spacer-G

 

Mechanical and pharmacological testing confirmed the favorable performances of the device, which are solid and allows partial weight-bearing and releases effective amount of antibiotic in the infected site.2,3,4,5,9 Soon after the first positive cases, the one-sized spacer was joined by a smaller and a bigger head size, which improved the head-acetabulum coupling and reduced dislocation. Then the longstem version was introduced, which allowed surgeons to use the device also in the absence of a proximal support, in the presence of large metaphyseal defects and after a transfemoral approach.12

KNEE, SHOULDER AND ELBOW SPACERS

The clinical success of the Spacer-G lead to the design of Spacer-K (Figure 1), a knee spacer with comparable performance. These temporary spacers are CE marked as Class III devices and are the first device of this type to have obtained FDA clearance (InterSpace Hip; InterSpace Knee; InterSpace Shoulder). Based on these experiences and taking advantage of the same principles, the shoulder (Spacer-S) (Figure 1) and the elbow spacer (Spacer-E) were designed.

BONE CEMENT ELUTION FROM PMMA

The mechanism, or mechanisms, of antibiotic elution from PMMA are not yet clear. Therefore, it is more correct to speak of experimental observations that show the conditions which lead to an increase or decrease in the release of antibiotic. Synthetically, keeping fixed solvent and temperature, the increase of the release occurs when there is an:

  • Increase in the concentration of the antibiotic in PMMA
  • Increase in the surface at the interface cement-solvent
  • Increase in the permeability of the cement matrix Permeability = porosity + chemical/ physical properties (of matrix) A reduction in the release will occur when in the opposite situation (Figure 3).

For example, the preparation of bone cement under vacuum determines a reduction in the cement porosity and therefore a reduction in the antibiotic release.10 In addition to the above mentioned parameters, other experimental observations show that the antibiotic (drug) molecule is able to migrate in the cement matrix even in the absence of a solvent following a diffusion behavior (Figure 4). The relation that better satisfies such experimental observations is the Fick’s equation:

J = D (C1 – C2)/ X

J is the molecular flux that is directly proportional to the diffusion coefficient (D), which depends from antibiotic matrix and temperature; interface area (A); concentration difference (C1 -C2) where C1> C2, and inversely proportional to the distance between C1 and C2 (X).

If we keep C and X constant, the formula becomes:

J = D A K

Therefore, if we want to increase the antibiotic release, it is sufficient to increase the diffusion coefficient D and the interface area A. This has been the route followed to design the new spacers.

HIGH-RELEASE MATRIX FOR THE SPACERS

In 2006, the distribution of the spacers with an increased antibiotic release started.1 The absolute amount of antibiotic in the devices is identical, but the new spacers have an increased release capacity. The release can be as high as 4-5x the release of the previous spacers. This result has been achieved in two ways: 1) the external surface (i.e., the interface area with the biological liquids) has been increased thanks to a special finishing that increases the interface area. Figure 5 shows the surfaces of Spacer-G stem before and after; 2) the bone cement matrix that includes the antibiotic made with a new generation of polymers structured to increase permeability.

Figure 5. Spacer-G stem: left, old version with smooth surface; right, new version with textured surface

 

Before turning into a compact and solid structure, the spacer is a powder of spheroidal particles made of a mixture of PMMA, barium sulphate and gentamicin sulphate. Only with a colorimetric method it is possible to discriminate the components. Figure 6 shows a group of spheroidal particles which constitutes the powder used to manufacture the spacers. The colorless particles are PMMA, the blue ones are gentamicin.

Figure 6. Bone cement powder: PMMA pearls are colorless, gentamicin sulphate pearls are blue

 

When the liquid monomer MMA is added to the powder, a mouldable dough is obtained that, in a few minutes, gets hard and solid. In the hardened mass, the spheroidal particles of PMMA cannot be distinguished any more, but the gentamicin ones can. Figure 7a shows the particles of gentamicin colored in red. Actually, these spheroidal particles act as micro reservoirs from which gentamicin flows outside the cement mass. Figure 7b shows the empty micro reservoir of genamicin after the contact with the solvent.

Figure 7. Cured gentamicin bone cement: A) reservoir with
gentamicin in red; B) empty reservoir (after contact with solvent)

 

CONCLUSION

The constant work carried out over the years has led to an extension of the use of bone cement in fields hardly imaginable a few years ago. Today, it is possible to manufacture with this material medical devices with different properties that can be modulated at pleasure (Figure 8). Bone cement as a drug delivery system can be designed and specific elution kinetics can be achieved.

This aspect expands the concept of cementation, and with the right synergy among specialists of different disciplines, it will be possible to strengthen the surgical and therapeutic tools and increase the healing expectations of the patient. •


REFERENCES

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