Large 3D porous scaffolds made of active hydroxyapatite obtained by biomorphic transformation of natural structures and process for obtaining them

Inventors

Tampieri, AnnaSprio, SimoneRuffini, Andrea

Assignees

Greenbone Ortho SrlConsiglio Nazionale delle Richerche CNR

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Publication Number

US-10688218-B2

Patent

Publication Date

2020-06-23

Expiration Date


Abstract

The present disclosure relates to a hydroxyapatite obtained from porous wood, having high compressive strength and dimensions suitable for clinical applications. The porous wood has a porosity of between about 60% and about 95%, said porosity being measured after subjecting the wood to a step of pyrolysis, and is selected from among rattan, pine, abachi, balsa, sipo, oak, rosewood, kempas and walnut wood. The hydroxyapatite may be substituted with one or more ions such as magnesium, strontium, silicon, titanium, carbonate, potassium, sodium, silver, gallium, copper, iron, zinc, manganese, europium, gadolinium. Also disclosed is a bone substitute comprising hydroxyapatite obtained from porous wood. The bone substitute is utilized for the substitution and regeneration of a bone or a bone portion, preferably for bones subjected to mechanical loads, such as long bones of the leg and arm, preferably the tibia, fibula, femur, humerus and radius. The invention relates also to a process for manufacturing a biomorphic hydroxyapatite scaffold from wood.

Core Innovation

The invention provides a biomorphic hydroxyapatite scaffold obtained from a wood template, where the wood is subjected to pyrolysis prior to measuring total porosity. The resulting scaffold is defined by a maximum length dimension greater than or equal to 2 cm and a total porosity of at least 20%, with an emphasized range of 60% to 95% in one embodiment. The porous wood template yields a biomorphic hydroxyapatite with a hierarchically organized pore architecture.

The scaffold derived from pyrolyzed wood has a hierarchically organized pore structure, including channel-like pores with interconnectivity between micro- and nano-pores. In one described refinement, 30% to 80% of total porosity corresponds to pores smaller than 150 μm in diameter, with the remaining porosity corresponding to pores larger than 150 μm in diameter. These structural constraints are directed to clinically relevant scaffold dimensions and pore organization.

The invention additionally defines enhanced mechanical strength and performance related to bone substitution and cellular response. The scaffold includes compressive strength measured along the longitudinal direction greater than 5 MPa, with described outcomes including longitudinal compressive strength up to about 16 MPa and an increased specific surface area in the range of about 9–20 m²/g. The described transformation process is multistep, including pyrolysis followed by carburization, oxidation, hydration, carbonation, and phosphatization, with a reduced-pressure carburization step stated to preserve micro/nano-porosity and improve pore distribution during scale-up to scaffolds with length ≥ 2 cm.

Claims Coverage

The independent claims cover two closely related subject matters: a biomorphic hydroxyapatite scaffold derived from pyrolyzed wood with a total porosity of at least 20% and a maximum length dimension of at least 2 cm, and a biomorphic hydroxyapatite derived from pyrolyzed wood with total porosity between 60% and 95%, a hierarchically organized pore structure, and longitudinal compressive strength greater than 5 MPa. Across the claim set, the main inventive elements are the pyrolysis-defined porous wood-to-hydroxyapatite biomorphic conversion with clinically relevant size, hierarchical pore structure, and directional compressive strength, optionally further specifying pore-size fractions, specific surface area, selected ion substitution, and enumerated wood sources.

Pyrolysis-defined biomorphic hydroxyapatite scaffold from porous wood with length ≥ 2 cm

A biomorphic hydroxyapatite scaffold obtained from a wood having a total porosity of at least 20%, said porosity being measured after subjecting the wood to a step of pyrolysis, said scaffold having a length, measured along a direction in which a dimension of the scaffold is maximum, greater than or equal to 2 cm.

Porosity range 60% to 95% with hierarchically organized pore structure and longitudinal compressive strength > 5 MPa

A biomorphic hydroxyapatite obtained from a wood having a total porosity of between 60% and 95%, said porosity being measured after subjecting the wood to a step of pyrolysis, wherein said hydroxyapatite comprises a hierarchically organized pore structure and a compressive strength, measured along the longitudinal direction, greater than 5 MPa.

Hierarchically organized pore structure with a pore-diameter fraction split

The biomorphic hydroxyapatite scaffold with a hierarchically organized pore structure where 30–80% of total porosity is pores smaller than 150 μm in diameter and the remaining porosity to 100% is pores larger than 150 μm in diameter.

Longitudinal compressive strength greater than 5 MPa

The biomorphic hydroxyapatite scaffold with a longitudinal-direction compressive strength greater than 5 MPa.

Specific surface area threshold

The biomorphic hydroxyapatite scaffold having a specific surface area (SSA) greater than 9 m²/g.

Partial substitution with selected ions

The biomorphic hydroxyapatite scaffold in which the hydroxyapatite is partially substituted with one or more selected ions from the group including magnesium, strontium, silicon, carbonate, sodium, potassium, silver, gallium, copper.

Wood component selected from enumerated species

The biomorphic hydroxyapatite scaffold having a wood component selected from the group including rattan, pine, abachi, balsa, sipo, oak, rosewood, kempas, and walnut wood.

Across the independent claims, the coverage focuses on biomorphic hydroxyapatite obtained from pyrolyzed porous wood with total porosity constraints and clinically relevant maximum length (≥ 2 cm in one claim), while also requiring a hierarchically organized pore structure and a longitudinal-direction compressive strength greater than 5 MPa. Dependent claims further narrow the subject matter by specifying pore-diameter fractions, a specific surface area threshold, partial hydroxyapatite ion substitution with selected ions, and enumerated wood species.

Stated Advantages

Enhanced mechanical strength, including longitudinal compressive strength greater than 5 MPa and up to about 16 MPa.

Increased specific surface area (SSA) of about 9–20 m²/g compared with stated prior art values.

Biologically relevant effects described as enhanced in vitro osteogenic gene expression and cellular outcomes, including improved MSC viability/gene markers and channel pores supporting angiogenesis.

Successful scale-up enabling scaffolds with length ≥ 2 cm while preserving micro/nano-porosity.

Documented Applications

Bone-substitute substitution/regeneration of load-bearing bones, including long bones (tibia, femur, humerus, radius; also fibula stated in the partial content) and also spine and cranial/maxillofacial sites.

Use as coated/loaded constructs is stated as an option.

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