IP Library Granted Patent US 11,491,261
Granted Patent B2
US 11,491,261 · App. 15/060,547 · Granted Nov 8, 2022

Coating scaffolds

Inventors: Leenaporn Jongpaiboonkit (Madison, WI); William L. Murphy (Madison, WI); Sharon Virginia Schulzki (Rancho Santa Fe, CA)
Assignee: Warsaw Orthopedic, Inc.
A61L27/32A61L27/34A61L27/3608A61L27/54A61L27/56A61L27/58A61L2300/104A61L2300/404A61L2400/18A61L2420/06A61L2430/02
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Quick Facts
Patent No.
US 11,491,261
App. No.
15/060,547
Granted
Nov 8, 2022
Kind
B2
Abstract

Provided are compositions and methods for a scaffold coated with a primer coating and a mineral coating. Also provided is a composition for a scaffold having a mineral coating similar to bone. Also provided is a method for mineral coating a scaffold so as to promote mineral coating of the scaffold with a plate-like nanostructure and a carbonate-substituted, calcium-deficient hydroxyapatite phase.

Claims (49)

1. A method for producing a mineral coated polycaprolactone (PCL) scaffold comprising:

providing a solvent comprising a chloroform or acetic acid, and a PCL scaffold, the PCL scaffold being in an amount from about 2 to about 3% w/v based on the % of the solvent;

dipping a polyetheretherketone (PEEK) mesh in the solvent;

drying the PCL scaffold and the PEEK mesh;

hydrolyzing the PCL scaffold and the PEEK mesh with from about 0.5 M to about 3 M NaOH to form a primer coated PCL scaffold;

contacting the primer coated PCL scaffold with a modified simulated body fluid, the modified simulated body fluid comprising 20 mM Tris, at least 5 mM CaCl 2 and at least 2 mM KH 2 PO 4 ;

incubating the primer coated PCL scaffold and the modified simulated body fluid for a period of time from about 2 to about 4 days under conditions sufficient to form a mineral coated PCL scaffold, wherein the modified simulated body fluid is adjusted to a pH of about 6.5 to about 7.2, and the modified simulated body fluid is changed daily and the primer coating of the PCL scaffold comprises a continuous or discontinuous coating and the primer coating promotes mineral coating of the PCL scaffold, wherein the mineral coating comprises a carbonate-substituted, calcium-deficient hydroxyapatite component, and the mineral coating has a plate-like nanostructure and a porosity between about 20% and about 28%;

incubating the primer coated PCL scaffold with a citric acid solution; and

incorporating silver particles with the mineral coated PCL scaffold by incubating the mineral coated PCL scaffold in a solution containing the silver particles such that the silver particles are configured to be linearly released from the mineral coated PCL scaffold.

2. A method for producing a mineral coated polycaprolactone (PCL) scaffold comprising:

providing a solvent comprising chloroform and a PCL scaffold, the PCL scaffold being in an amount being in an amount of about 2.5% w/v based on the % of the solvent;

dipping a polyetheretherketone (PEEK) mesh in the solvent;

drying the (PCL) scaffold and the PEEK mesh for about 10 minutes;

hydrolyzing the (PCL) scaffold and the PEEK mesh with 0.5 M NaOH for about 30 minutes;

incubating the (PCL) scaffold and the PEEK mesh for a period of time under conditions sufficient to form a primer coated (PCL) scaffold over the PEEK mesh;

contacting the primer coated (PCL) scaffold over the PEEK mesh with a modified simulated body fluid, the modified simulated body fluid comprising 20 mM Tris, at least 5 mM CaCl 2 and at least 2 mM KH 2 PO 4 ;

incubating the primer coated (PCL) scaffold over the PEEK mesh and the modified simulated body fluid for 2 days under conditions sufficient to form a mineral coated primer coated (PCL) scaffold, by adjusting the modified simulated body fluid to a pH of about 6.5 to about 7.2, wherein the modified simulated body fluid is changed daily;

wherein the mineral coating comprises a plate-like nanostructure and a carbonate-substituted, calcium deficient hydroxyapatite component and the mineral coating has a porosity between about 20% and about 28%;

incubating the primer coated (PCL) scaffold over the PEEK mesh with a citric acid solution; and

incorporating silver nanoparticles with the (PCL) scaffold over the PEEK mesh such that the mineral coated primer coated (PCL) scaffold has antimicrobial, antibacterial, biostatic, or anti-infection properties and the average surface roughness of about 132 μm.

3. The method of claim 1 , wherein

the primer coating comprises a thin film; or

the primer coating has a thickness of about 1 μm to about 50 μm.

4. The method of claim 1 , further comprising combining NaCl, KCl, MgCl 2 , MgSO 4 , and NaHCO 3 , with the CaCl 2 , Tris, and KH 2 PO 4 to form the modified simulated body fluid.

5. The method of claim 4 , wherein:

(i) NaCl has a concentration of about 100 mM to about 200 mM; KCl has a concentration of about 1 mM to about 8 mM; MgCl 2 has a concentration of about 0.2 mM to about 5 mM; MgSO 4 has a concentration of about 0.2 mM to about 5 mM; NaHCO 3 has a concentration of about 1 mM to about 100 mM; CaCl 2 has a concentration of about 5.5 mM to about 20 mM; and KH 2 PO 4 has a concentration of about 2.2 mM to about 10 mM; or

(ii) NaCl has a concentration of about 141 mM; KCl has a concentration of about 4.0 mM; MgCl 2 has a concentration of about 1.0 mM; MgSO 4 has a concentration of about 0.5 mM; NaHCO 3 has a concentration of about 4.2 mM; CaCl 2 has a concentration of 5 mM; KH 2 PO 4 has a concentration of 2.0 mM.

6. The method of claim 1 , wherein incubating the primer coating composition and the (PCL) scaffold for a period of time sufficient to form a primer coated scaffold is about 2 days.

7. The method of claim 1 , wherein incubating the (PCL) scaffold or incubating the primer coated (PCL) scaffold and the modified simulated body fluid comprises:

(i) heating the modified simulated body fluid to physiologic temperature or adjusting to a physiologic pH wherein the physiologic temperature is about 37° C. or physiological pH is about 6.8;

(ii) incubating the (PCL) scaffold in the primer coating composition comprises replacing the primer coating composition, replenishing the primer coating composition, removing the primer coating composition, or adding the primer coating composition; or

(iii) incubating the (PCL) scaffold in the primer coating composition comprises maintaining a concentration of primer coating composition, wherein maintaining the concentration of primer coating composition comprises replacing, replenishing, removing, or adding polymer, solvent, or a combination thereof.

8. The method of claim 1 , wherein incubating the primer coated (PCL) scaffold or (PCL) scaffold in the modified simulated body fluid comprises:

(i) replacing the modified simulated body fluid, replenishing the modified simulated body fluid, removing the modified simulated body fluid, or adding the modified simulated body fluid; or

(ii) maintaining a concentration of modified simulated body fluid, wherein maintaining the concentration of modified simulated body fluid comprises replacing, replenishing, removing, or adding NaCl, KCl, MgCl 2 , MgSO 4 , NaHCO 3 , CaCl 2 , or KH 2 PO 4 , or a combination thereof.

9. The method of claim 1 , wherein the (PCL) scaffold comprises:

(i) a pore diameter between about 200 μm and about 525 μm; between about 25 μm to about 65 μm; or more than about 50 μm; or

(ii) a macrochannel length of more than about 100 μm.

10. The method of claim 1 , wherein the mineral coating comprises:

(i) about 0.1 to about 18 Ca/P or about 1.1 to about 1.76 Ca/P (calcium to phosphate ratio);

(ii) about 1.67 to about 1.76 Ca/P; about 1.1 to about 1.3 Ca/P; or about 1.37 to about 1.61 Ca/P; or

(iii) a crystallinity of about 9% to about 100%; about 90% to about 100%; or about 96.5%.

11. The method of claim 2 , further comprising combining NaCl, KCl, MgCl 2 , MgSO 4 , NaHCO 3 , with the CaCl 2 , and KH 2 PO 4 to form the modified simulated body fluid, wherein

(i) NaCl has a concentration of about 100 mM to about 200 mM; KCl has a concentration of about 1 mM to about 8 mM; MgCl 2 has a concentration of about 0.2 mM to about 5 mM; MgSO 4 has a concentration of about 0.2 mM to about 5 mM; NaHCO 3 has a concentration of about 1 mM to about 100 mM; CaCl 2 has a concentration of about 5.5 mM to about 20 mM; and KH 2 PO 4 has a concentration of about 2.2 mM to about 10 mM; or

(ii) NaCl has a concentration of about 141 mM; KCl has a concentration of about 4.0 mM; MgCl 2 has a concentration of about 1.0 mM; MgSO 4 has a concentration of about 0.5 mM; NaHCO 3 has a concentration of about 4.2 mM; CaCl 2 has a concentration of 5 mM; and KH 2 PO 4 has a concentration of 2.0 mM.

12. The method of claim 2 , wherein the (PCL) scaffold comprises:

(i) a pore diameter between about 200 μm and about 525 μm, between about 25 μm and about 65 μm; or more than about 50 μm; or

(ii) a macrochannel length of more than about 100 μm.

13. The method of claim 1 , wherein the modified simulated body fluid is adjusted to a physiologic pH of about 6.8.

Assignments (4)
CORRECTIVE ASSIGNMENT TO CORRECT THE NATURE OF CONVEYANCE PREVIOUSLY RECORDED AT REEL: 50085 FRAME: 457. ASSIGNOR(S) HEREBY CONFIRMS THE ASSIGNMENT. Recorded Aug 29, 2019
From: TISSUE REGENERATION SYSTEM, INC
To: WARSAW ORTHOPEDIC, INC.
Reel/Frame 050234/0316 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 19, 2019
From: TISSUE REGENERATION SYSTEM, INC
To: WARSAW ORTHOPEDIC, INC.
Reel/Frame 050085/0457 →
MERGER AND CHANGE OF NAME Recorded Jul 15, 2019
From: TISSUE REGENERATION SYSTEMS, INC.; TRS HOLDINGS LLC
To: TRS HOLDINGS LLC
Reel/Frame 049753/0370 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Aug 4, 2016
From: JONGPAIBOONKIT, LEENAPORN; MURPHY, WILLIAM L.; SCHULZKI, SHARON VIRGINIA
To: TISSUE REGENERATION SYSTEMS, INC.
Reel/Frame 039346/0661 →
Continuity (3)
Provisional Application 62197212 · Jul 27, 2015
Provisional Application 62127762 · Mar 3, 2015
Related Publication 20160271296A1 · Sep 22, 2016