Nerve repair scaffolds having high microchannel volume and methods for making the same
Tissue scaffolds for neural tissue growth have a plurality of microchannels disposed within a sheath. Each microchannel comprises a porous wall having a thickness of ≤about 100 μm that is formed from a biocompatible and biodegradable material comprising a polyester polymer. The polyester polymer may be polycaprolactone, poly(lactic-co-glycolic acid) polymer, and combinations thereof. The tissue scaffolds have high open volume % enabling superior (linear and high fidelity) neural tissue growth, while minimizing inflammation near the site of implantation in vivo. In other aspects, methods of making such tissue scaffolds are provided. Such a method may include mixing a reduced particle size porogen with a polymeric precursor solution. The material is cast onto a template and then can be processed, including assembly in a sheath and removal of the porogen, to form a tissue scaffold having a plurality of porous microchannels.
1. A method of making a tissue scaffold for neural tissue growth, the method comprising:
admixing (i) a porogen having an average particle size of less than or equal to about 40 μm with (ii) a polymeric precursor solution comprising a biocompatible and biodegradable polyester polymer precursor and a first solvent, to form a suspension;
contacting a template with the suspension to coat at least one surface of the template;
volatilizing at least a portion of the first solvent to form a coating;
removing the coating from the template; to create a microchannel;
assembling the microchannel inside a sheath with a plurality of other microchannels; and
removing the porogen to form a plurality of porous microchannels disposed within sheath thus creating the tissue scaffold.
2. The method of claim 1 , wherein the method further comprises cutting the coating to form a microchannel prior to the assembling.
3. The method of claim 1 , wherein the biocompatible and biodegradable polyester polymer is selected from the group consisting of: polycaprolactone, poly(lactic-co-glycolic acid) polymer, and combinations thereof.
4. The method of claim 1 , wherein the porogen is a material that is brittle and soluble in a second solvent, but does not dissolve in the first solvent.
5. The method of claim 4 , wherein the porogen is selected from a group consisting of: sodium chloride, calcium chloride, potassium chloride, sugars, and combinations thereof.
6. The method of claim 1 , further comprising ball milling the porogen before the admixing.
7. The method of claim 1 , wherein the admixing comprises ball milling the porogen, the polyester polymer precursor, and the solvent together for a duration of greater than or equal to about 1 minute to less than or equal to about 60 minutes.
8. The method of claim 1 , wherein the template has a rod or a fiber shape and comprises a metal selected from a group consisting of: brass alloy, copper, stainless steel, and combinations thereof.
9. The method of claim 1 , further comprising coating the surface of the porous coating with a biofunctional material for promoting growth of the neural tissue selected from the group consisting of: fibronectin, keratin, laminin, collagen, and combinations thereof.
10. The method of claim 1 , further comprising exposing the porous coating with a delamination agent to facilitate the removing of the coating from the template.
11. The method of claim 1 , wherein the polymeric precursor solution comprises:
(i) greater than or equal to about 0.5 weight % to less than or equal to about 5 weight % of polycaprolactone in the first solvent; or
(ii) greater than or equal to about 1 weight % to less than or equal to about 15 weight % of poly(lactic-co-glycolic acid) polymer in the first solvent.
12. The method of claim 1 , wherein the suspension comprises a porogen comprising sodium chloride at greater than 0 volume % to less than or equal to about 80 volume % and either:
(i) greater than 0 volume % to less than or equal to about 80 volume % of polycaprolactone in the suspension; or
(ii) greater than or equal to about 0 volume % to less than or equal to about 95 volume % of poly(lactic-co-glycolic acid) polymer in the suspension.