Hydroxyapatite tissue filler and its preparation and use

Abstract

The invention pertains to a biocompatible composition, suitable for use in soft or hard tissue augmentation, wherein the composition is an aqueous suspension containing a carrier fraction of ceramic particles of less than 15 &mgr;m and an augmentation fraction of ceramic particles of at least 20 &mgr;m. The ceramics typically comprise calcium phosphate. The composition is a may be used in soft tissue repair as well as hard bone replacement. It advantageously avoids the need for foreign body materials which are conventionally applied to stabilize augmentation suspensions.

Description

FIELD OF THE INVENTION[0001]The invention pertains to biocompatible compositions containing ceramic particles, in particular hydroxyapatite, for soft and hard tissue augmentation, especially for bone regeneration and treatment of skin contour deficiencies, and for cosmetic use in plastic surgery, in particular for filling soft tissue voids or creating soft tissue augmentation.BACKGROUND OF THE INVENTION[0002]Since long biocompatible materials have been applied in augmenting soft tissue in the practice of plastic and reconstructive surgery. These biomaterials are commonly delivered to the tissue site where augmentation is desired by means of an injectable composition that comprises the biomaterial and a biocompatible fluid, wherein the fluid acts as a lubricant to improve the delivery of the biomaterial suspension.[0003]Since the mid-eighties polymethylmethacrylate (PMMA) has been studied as a soft tissue augmentation device, replacing then popular collagen. The permanent character o...

AI Technical Summary

Benefits of technology

[0008]It is a further object of the invention to provide such a biocompatible composition that, if applied in soft tissue augmentation, is resorbable over time periods of 1-2 years in a human being of about 40 years of age. If applied in hard tissue augmentation material, it should dissolve in the human body over time, but slow enough so as to allow for replacement with growing tissue cells.

[0011]It is now found that it is possible to stabilize augmentation particles, independent of their size and porosity, by adding them to an aqueous gel or suspension of small, unagglomerated ceramic particles. Undesired conventional stabilizing agents can be dispensed with.

[0022]The stability of the suspension may be further improved selecting the material for the smaller particles on the basis of its interfacial properties, which may be fine-tuned by the preparation route. Since augmentation and carrier particles are present for different reasons, these materials do not necessarily have to be of the same origin. In fact, a selection of different materials may lead to better results, provided that the augmentation and carrier particles are chosen from the above-listed biocompatible materials.

[0025]Where lower resorbability rates are desired, it is preferred that the augmentation materials resemble perfect spheres, because of the optimum area-to-volume ratio and the positive effect on prevention of inflammations related therewith. The terms “rounded” or “smooth” as used herein refers to the fact even though the present particles are not perfect spheres, they do not have any sharp or angular edges, in order to improve injectability if so required. Surface milling and the like can improve surface smoothness.

[0028]Where injectability is an issue, it is preferred to use a narrow or even equivalent particle size range of augmentation particles due to the fact that a distribution of such smooth and round particles reduces friction, and facilitates the ease of injecting the particles by needle from a syringe into the skin tissue at the desired augmentation site. This is in contrast to the use of the more porous, textured, irregularly shaped particles which tend to increase the frictional forces, and are much more difficult to deliver by injection. Hence, it is preferred that the size difference between the largest and the smallest (soft tissue) augmentation particle does not exceed about 35 μm. Further, it may be desirable to minimize surface porosity to below 30%; with elimination of jagged irregular surfaces, the ability of the smooth round particles to flow easily in contact with each other is maximized.

[0034]In addition to the augmentation material, the composition may optionally comprise an amount of active ingredients. These active ingredients can include substances that may provide therapeutic effects to the process of augmentation or biological or physiological responses to the dermal augmentation. An example of such therapeutic agent is an anti-inflammation agent that prevents or reduces the effect of inflammations associated with dermal augmentation, an anti-bacterial, anti-fungal or anti-histamine agent. It may also involve cell adhesion promoters, which enhance the adhesiveness of cells to the surface of the particles. Another suitable active ingredient is a local anaesthetic agent. For the purpose of osteogenesis, the ceramic filler of the invention may be admixed with an osteoinductive factor (OFE), considered as one of the active ingredients optionally included in the composition. OFE useful in the composition of the invention is known to the person skilled in the art. The skilled person can easily recognize whether ingredients of the composition are included for augmentation or other purposes.

Problems solved by technology

However, it is discovered recently that the injection of PMMA microspheres causes all kinds of complications in time, to a large extent related to the non-biodegradable properties.

Moreover, it is now believed that the permanent impact of filler materials in tissue is undesired, since the tissue itself is subject to ageing (see e.g. E. Haneke, “Skin rejuvenation without a scalpel. I. Fillers”, J Cosmetic Dermatology; 5: 157-167 (2005); K. De Boulle, “Management of complications after impantation of fillers”, J Cosmetic Dermatology; 3: 2-15 (2004).

Further, hydroxyapatite has very low immunogenicity.

However, the use of foreign body carrier materials renders these injectable hydroxyapatite compositions unattractive.