Biomaterial

Abstract

A biomaterial, particularly for tissue regeneration, includes an open, porous bioresorbable first material portion and a second material portion that is stiffer than the first material portion, wherein the volume fraction of the stiffer material is less than 30% of the total volume of the biomaterial, and the structural stiffness of the second material portion is at least 10 times greater than that of the first material portion.

Claims

1. A biomaterial comprising an openly porous, bioabsorbable first material fraction and a second material fraction that is stiffer than the first material fraction and forms a load-bearing support structure, wherein the second material fraction is an integral part of the biomaterial surrounded by the first material fraction, as in an endoskeleton, such that the first material fraction is structurally integrated into the second material fraction in a form-fitting manner, wherein the volume fraction of the stiffer material is less than 30% of a total volume of the biomaterial, the total volume comprising the volume of the biomaterial and the volume of voids enclosed by the biomaterial, and wherein the structural stiffness in MPa of the second material fraction is at least 10 times higher than the structural stiffness in MPa of the first material fraction as determined using the same methodology.

2. The biomaterial according to claim 1, wherein at least one material fraction is elastically deformable.

3. The biomaterial according to claim 1, wherein both material fractions are elastically deformable.

4. The biomaterial according to claim 1, wherein the volume fraction of the stiffer material is less than 25% of the total volume of the biomaterial.

5. The biomaterial according to claim 1, wherein the structural stiffness of the second material fraction is 100 times higher than that of the first material fraction.

6. The biomaterial according to claim 1, wherein an average elongation between 1% and 100% or compression between 1% and 30% is caused by tissue forces acting after implantation in the first material fraction.

7. The biomaterial according to claim 6 for cartilage regeneration, in which tissue forces acting on the biomaterial after implantation lead to a compression of the first material fraction between 4-12%.

8. The biomaterial according to claim 6 for bone regeneration, in which tissue forces acting on the biomaterial after implantation lead to a compression of the first material fraction between 0.04-4%.

9. The biomaterial according to claim 1, wherein the first material fraction serves as a support material for cell regeneration and as cell-controlling material and the second material fraction serves as a mechanically stabilizing element.

10. The biomaterial according to claim 1, wherein at least one material fraction has a structure configured to direct a regeneration process along a predetermined direction.

11. The biomaterial according to claim 1, wherein the first material fraction has a first region configured to direct a regeneration process along a first direction and the second material fraction has a second region configured to direct a regeneration process along a second direction different from the first direction.

12. The biomaterial according to claim 1, wherein at least one material fraction has a structure comprising repetitive units.

13. The biomaterial according to claim 1, wherein at least one material fraction contains components visible using X-ray, computer tomography, or magnetic resonance imaging methods.

14. The biomaterial according to claim 1, wherein at least one material fraction is deformable by an external stimulus for regeneration promotion.

15. The biomaterial according to claim 1, wherein the stiffness of the second material fraction is highest in the direction in which the largest forces act on the material after implantation in a tissue.

16. The biomaterial according to claim 1, wherein the second material fraction has an architecture configured to realize a predetermined macroscopic material stiffness.

17. The biomaterial according to claim 1, wherein the second material fraction comprises a plurality of structural elements selected from the group consisting of pore walls and webs, each structural element having a diameter differing from an average diameter of all the structural elements by less than a factor of two.

18. A method for producing the biomaterial according to claim 1, wherein the second material portion of an implant for the regeneration of a specific tissue is adjusted so that the elongations required for the regeneration of this tissue result in the first material fraction in the body and a collapse of the first material fraction is prevented.

19. The biomaterial according to claim 10, wherein the structure has an aspect ratio of at least threefold so that a largest distance and a smallest distance between structural elements of the structure along all spatial directions differs by at least threefold.

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) Several embodiments are shown in the drawing and are explained in more detail below. Shown are

(2) FIG. 1 a three-dimensional view of an openly porous, bioresorbable first material fraction,

(3) FIG. 2 a three-dimensional view of a second material fraction, which is stiffer than the first material fraction,

(4) FIG. 3 a three-dimensional view of a combination of first and second material fraction,

(5) FIG. 4 a three-dimensional view of a combination of first and second material fraction having different structures,

(6) FIG. 5 a view of the integration of the combination shown in FIG. 3 into a tissue region,

(7) FIG. 6 a three-dimensional view of a mechano-hybrid scaffold,

(8) FIG. 7 a section through the mechano-hybrid scaffold shown in FIG. 6,

(9) FIG. 8 a side view of the compressed mechano-hybrid scaffold shown in FIG. 6,

(10) FIG. 9 two views of a structural element of the second material component as a basis for computer simulations,

(11) FIG. 10 the lower limit values of the relative structural stiffness of the structural element shown in FIG. 9 as a table,

(12) FIG. 11 a pure collagen scaffold (a, 1) and a mechano-hybrid scaffold (a, 2) after cutting the prototypes for mechanical testing and a support structure produced by means of SLM before introduction into the mechano-hybrid scaffold (b),

(13) FIG. 12 images of the pure collagen scaffold (a) and of the mechano-hybrid scaffold (b) after wetting with aqueous buffer solution and the result of the mechanical compression test (c) and

(14) FIG. 13 the structural stiffness over the porosity.

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

(15) The first material fraction shown in FIG. 1 has a directed pore structure. This serves as a guide structure and at the same time represents the actual cell substrate having optimized mechanical and structural properties (for example, pore diameter) and thus the material component for induction of the regeneration processes. The mechanical properties are optimized for the cellular processes of migration, matrix formation and differentiation (intrinsic biomechanical and structural signals).

(16) The second material fraction shown in FIG. 2 (secondary structure), in the illustrated embodiment, is also the structurally anisotropic, load-bearing support structure. It has no direct influence on the cellular processes. However, the higher stiffness of this component ensures the macroscopic integrity of the first material fraction. The stable structure realizes a spanning function and prevents the collapse of the first material fraction serving as an inner guide structure during the tissue formation and remodeling processes. In addition, the mechanical elongations that arise due to the locally acting musculoskeletal forces in the first material fraction are adjusted via the stiffness of the second material fraction. Elongation values are set which support the differentiation into the desired tissue types (for example, cartilage or bone).

(17) The mechano-hybrid scaffold shown in FIG. 3 represents a three-dimensional combination of first and second material fraction and FIG. 4 represents an embodiment in which the different requirements for new tissue formation (cartilage to bone) are realized by two regions of different properties. Here, the extensibility according to the cellular requirements in the lower region of the scaffold for the bony regeneration is smaller than in the upper region for the cartilage regeneration.

(18) FIG. 5 shows a view for the integration of the combination shown in FIG. 3 into a tissue region of a bone cartilage defect, wherein the use of the embodiment according to FIG. 4 is an even more advantageous variant for the regeneration of the two tissue types bone or cartilage.

(19) The mechano-hybrid scaffold shown in FIGS. 6 to 8 consists of a material fraction, for example, of collagen and a second material fraction, for example, of PCL. The structure of the second material fraction was optimized in terms of mechanical and structural properties (anisotropy, defined stiffness, high porosity, no struts oriented perpendicular to the longitudinal direction/pore direction). The hierarchical structure was created by duplication of unit cells from the first and second material components. The deformation from load shown in FIG. 8 was simulated by means of the finite element method for the design process to achieve the desired beneficial elongations.

(20) In one embodiment, a soft collagen scaffold, as a first material fraction, having vertically directed pores was combined with a 3D printed support structure as the second material fraction. The support structure was made of polyamide (PA) by means of SLM (selective laser melting). The diameter of the pores in the support structure (that is, the diameter of a honeycomb of the second material fraction) was approximately 50× greater than the diameter of the pores in the first material fraction, the collagen scaffold. The mechano-hybrid scaffold (FIG. 11 a, Scaffold 2) has been prepared by producing a very soft collagen scaffold having directed pores within the support structure (FIG. 11 b).

(21) While the pure collagen scaffold collapses after wetting with aqueous solution (phosphate buffer) and thus alters its external shape (FIG. 12a), the mechano-hybrid scaffold shows no change in the outer geometry as a sign of the spanning function of the secondary structure (=skeleton!!) (FIG. 12b). FIG. 12 thus shows the mechanical stabilization of a collagen scaffold by introducing a 3D printed support structure made of PA to generate a mechano-hybrid scaffold. The images of FIG. 12 show the pure collagen scaffold (a) and the mechano-hybrid scaffold (b) after wetting with aqueous buffer solution. The result of the mechanical compression test shows the more than 1000-fold increase in scaffold stiffness by introducing the support structure (c). The elastic modulus of the pure collagen scaffold and the collagen/PA hybrid scaffold was determined by means of uniaxial mechanical compression testing in an open reservoir with aqueous solution (“unconfined compression test”). The elastic modulus E was analyzed in the linear region of the stress-strain curve. Mechanical testing revealed an increase in macroscopic stiffness from E=0.3 (±0.1) kPa (pure collagen scaffold) to 550 (±64) kP (mechano-hybrid scaffold), that is, more than 1000 fold (see FIG. 12c).