Inventors: Barrows, Thomas H.; Austell, GA, United States of America
Assignee: Aderans Research Institute, Inc., Beverly Hills, CA, United States of America
Publication date: 2007-04-03
Invention summary:
Porous, bio-absorbable scaffold for tissue engineering of human hair follicles, comprises bio-absorbable material.
Abstract:
Porous, bioabsorbable scaffolds for tissue engineering of human hair follicles, methods for their manufacture and methods of their use in creating new hair.
First Claim:
A porous scaffold comprising a bioabsorbable polymer and hair follicle progenitor cells; wherein the scaffold is about the shape of a hair follicle; wherein the porous scaffold comprises a fibrous structure; and wherein the fibrous structure comprises fibers that are bonded together.
Description:
In one aspect, the present invention comprises porous bioabsorbable scaffolds that are in the approximate shape of the normal hair follicle bulb, and designed to promote the formation of a hair follicle when seeded with hair follicle cells and implanted intradermally into a living host.
The scaffolds of the present invention are preferably comprised of a bioabsorbable polymer, selected from any of a wide variety of synthetic and natural polymers that are commonly used in clinical practice and in biomedical research. The scaffolds are more preferably comprised of a polymer selected from the group consisting of poly(lactic acid), poly(glycolic acid), poly(trimethylene carbonate), poly(amino acid)s, tyrosine-derived poly(carbonate)s, poly(carbonate)s, poly(caprolactone), poly(para-dioxanone), poly(ester)s, poly(ester-amide)s, poly(anhydride)s, poly(ortho ester)s, poly(amino acid)s, collagen, gelatin, serum albumin, proteins, carbohydrates, poly(ethylene glycol)s, poly(propylene glycol)s, poly(acrylate ester)s, poly(methacrylate ester)s, poly(vinyl alcohol), and copolymers, blends and mixtures of said polymers.
When the scaffold is comprised of a synthetic polymer, it is preferably a synthetic polymer formed from any one or combination of the following monomers: L-lactide, d,l-lactide, glycolide, trimethylene carbonate, caprolactone, and para-dioxanone. Other preferred synthetic polymers for use in making the scaffold of the present invention include poly(ethylene glycol), poly(vinyl alcohol), poly(acrylic acid) and other water soluble polymers that have been crosslinked with degradable linkages and any bioabsorbable hydrogel that has been modified to support cell attachment.
When the scaffold is comprised of a crosslinked or otherwise insoluble or insolubilized naturally occurring polymer, it is preferably a polymer selected from the group consisting of hyaluronic acid, human serum albumin, collagen, gelatin, cellulose derivatives, starch, dextrin, chitosan, and other proteins, glycoproteins, lipoproteins, polysaccharides, and biopolymers.
A preferred scaffold of the present invention has an inner surface which is preferably in the shape of the outer surface of a hair root or bulb. The inner surface of the scaffold is preferably porous. The porosity of the scaffold is preferably sufficient to enable hair follicle cells to be adsorbed by the inner surface of the scaffold when placed into contact therewith, e.g., in a cell culture solution.
Methods of making the porous bioabsorbable scaffolds of the present invention are disclosed herein, below. Such methods include procedures for creating porosity in bioabsorbable materials and procedures for molding, shaping, or sculpting said porous scaffolds into the desired configuration. The present invention is not limited to scaffolds produced according to the specific methods disclosed herein, below, as it is contemplated that the scaffolds could be made using variations of the disclosed methods, or by adapting known means used to manufacture porous polymers.
Any one of a number of different means are suitable for creating the porosity of the scaffolds of the present invention. A preferred method for creating porosity involves the use of “blowing agents”. These are chemical additives that decompose at known temperatures with the liberation of gases that cause foaming in the molten polymer and porosity in the resultant cooled material. A number of useful blowing agents are commercially available under the trade name of Celogen™ (Uniroyal Chemical Co.). One example of a traditional blowing agent is azodicarbonamide. Another blowing agent that may be especially useful in the present invention due to its compatibility with bioabsorbable polymers is urea dicarboxylic acid anhydride, described in U.S. Pat. No. 4,104,195, the teachings of which are incorporated herein. The use of blowing agents can produce both open cell and closed cell foams. In the present invention open cells are desired and closed cells are to be avoided. Thus the conditions used in the manufacture of the porous coating are preferably optimized to achieve an open cell structure known as “reticulated” foam. The porosity of the scaffold is preferably due to interconnected pores in the size range of 0.1 to 1,000 microns, more preferably in the size range of 1 to 500 microns.
In an alternative embodiment, the porosity of the scaffold is due to the fact that the scaffold has a fibrous structure. When the scaffold has a fibrous structure, the fibers are preferably bonded together. The fibers of such a preferred structure are more preferably comprised of a core and sheath structure, said sheath being lower melting than said core, and bonded together by means of inter-fiber welds in the sheaths at points of contact.
Scaffolds of the present invention can be used to engineer new hair follicles in a number of ways. In general, the appropriate cells can be seeded on the scaffold and either implanted immediately into the scalp or allowed to multiply in culture on the scaffold prior to implantation. The implantation procedure can be the same technique that hair transplant surgeons currently use to implant single follicles or “mini-grafts”. For example, a laser can be used to bore a small hole in the scalp to precisely the desired depth and the cell-seeded scaffold can simply be planted in the hole. As these implanted cells grow they orchestrate the neo-genesis of a new hair follicle. The bioabsorbable scaffold then degrades and is eliminated from the site as the implant matures into a normal, hair-producing follicle.
The cells used to seed the scaffold can be taken from follicles biopsied from the patient or from organ donor follicles. This later option is known to be feasible due to recent research results. Follicle progenitor cells from a human donor were successfully transplanted into an unrelated human recipient where they initiated the formation of new follicles that grew hair. This finding, entitled “Trans-gender induction of hair follicles”, was reported by A. M. Reynolds, C. Lawrence, P. B. Caerhalmi-Friedman, A. M. Christiano and C. A. B. Jahoda in Nature, 402, 33–34, Nov. 4, 1999, the teachings of which are incorporated by reference herein. A distinct advantage of the present invention is the ability to multiply the cells in culture before seeding them on the scaffold implants. This both maximizes the number of scaffolds that can be seeded from each harvested follicle and minimizes the labor of dissecting follicles to obtain the desired progenitor cells.
Background:
Male pattern baldness is a common condition that is often treated by hair transplant surgery. In this procedure hair follicles from areas of the scalp that are not within the baldness pattern are excised and re-implanted to create the illusion of a fuller head of hair. In fact, no new hair is created by this procedure, which is limited by the number of follicles that can be harvested for re-distribution. Thus, there is a great need, satisfied by the present invention, for a means for stimulating the growth of multiple new hair follicles in the scalp of an individual.
Summary:
This invention relates to new bioabsorbable scaffolds that are useful for the tissue engineering of new hair follicles and to methods for their manufacture and to methods of their use in creating new hair. More specifically it relates to new and useful bioabsorbable porous structures that have the correct architecture to facilitate culturing of the appropriate follicle progenitor cells and their development into normal, functional, hair-producing follicles. The invention also relates to methods of making and using bioabsorbable scaffolds to implant and grow new hair follicles in vitro and in vivo. |
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