SURGICAL SUTURES INCORPORATED WITH STEM CELLS OR OTHER BIOACTIVE MATERIALS

• US 20090318962A1
• Filed: 06/23/2009
• Published: 12/24/2009
• Est. Priority Date: 06/24/2008
• Status: Active Grant

• Current Assignee: Bioactive Surgical, Inc.
• Original Assignee: Bioactive Surgical, Inc.
• Inventors: SCHON, Lew C., PINGEL, Laura J., SPEDDEN, Richard H.
• Granted Patent: US 8,876,864 B2
• Time in Patent Office: Days
• US Class Current: 606/228
• CPC Class Codes: A61B 17/06114 Packages or dispensers for needles or sutures packages for sharps A61B50/3001; for dental floss A61C15/043; packages for needles in general B65D85/24
• CPC Class Codes: A61B 17/06166 Sutures suture materials A61L17/00; manufacture of artificial threads D01D; treatment of threads D06M
• CPC Class Codes: A61B 2017/00884 enhancing wound closure
• CPC Class Codes: A61B 2017/00893 pharmaceutically effective
• CPC Class Codes: A61B 2017/06185 hollow or tubular
• CPC Class Codes: A61L 17/005 containing a biologically active substance, e.g. a medicament or a biocide
• CPC Class Codes: A61L 17/06 At least partially resorbable materials
• CPC Class Codes: A61L 2300/404 Biocides, antimicrobial agents, antiseptic agents
• CPC Class Codes: A61L 2300/414 Growth factors
• CPC Class Codes: A61L 2300/42 Anti-thrombotic agents, anticoagulants, anti-platelet agents
• CPC Class Codes: A61L 2300/45 Mixtures of two or more drugs, e.g. synergistic mixtures
• CPC Class Codes: A61L 2300/604 Biodegradation
• CPC Class Codes: A61L 2300/64 Animal cells
• CPC Class Codes: D06B 1/10 by contact with a member carrying the treating material

Abstract

Materials and Methods for immobilizing bioactive molecules, stem and other precursor cells, and other agents of therapeutic value in surgical sutures and other tissue scaffold devices are described herein. Broadly drawn to the integration and incorporation of bioactive materials into suture constructs, tissue scaffolds and medical devices, the present invention has particular utility in the development of novel systems that enable medical personnel performing surgical and other medical procedures to utilize and subsequently reintroduce bioactive materials extracted from a patient (or their allogenic equivalents) to a wound or target surgical site.

Claims

1. A surgical suture or elongate linear tissue scaffold having an exterior surface and interior core, wherein:

(i) said interior core is composed of one or more concentric inner zones, one or more of which contain a concentration of bioactive material selected from the group consisting of biological cells and therapeutic agents dispersed therethrough; and

(ii) said exterior surface is composed of one or more concentric outer zones or layers radially disposed about said interior core to control the migration of said bioactive material from said interior core to said exterior surface.

2. The suture or scaffold of claim 1, wherein said exterior surface comprises porous structure.

3. The suture or scaffold of claim 2, wherein said porous structure comprises a woven sheath.

4. The suture or scaffold of claim 3, wherein said woven sheath comprises a plurality of interwoven filaments having divergent biodegradation properties.

5. The suture or scaffold of claim 2, wherein said exterior surface further comprises a material having sufficiently high viscosity or surface tension such that the pores of said porous structure are obstructed when said material is disposed thereabout.

6. The suture or scaffold of claim 2, wherein said exterior surface further comprises a layer of particulate material disposed about said porous structure and obstructing the pores thereof.

7. The suture or scaffold of claim 6, wherein said exterior surface further comprises a layer of a biodegradable material disposed about said layer of particulate material that retains said particulate material within the pores of said porous structure.

8. The suture or scaffold of claim 1, wherein said exterior surface comprises one or more layers of a porous or non-porous film.

9. The suture or scaffold of claim 1, wherein said exterior surface is comprised of one or more layers of a biodegradable material disposed about said interior core that initially impairs migration of said bioactive material from the interior core and across said exterior surface but, upon insertion into a biological environment, degrades to a degree that permits migration of material across said exterior surface.

10. The suture or scaffold of claim 1, wherein said exterior surface comprises one or more layers of a material having sufficiently high viscosity or surface tension, said material obstructing the pores of a porous interior core and inhibiting the migration of said bioactive material out from said interior core.

11. The suture or scaffold of claim 1, wherein said exterior surface comprises one or more layers of particulate material disposed about a porous interior core that inhibits the migration of said bioactive material out from said interior core.

12. The suture or scaffold of claim 11, wherein said particulate material inhibits migration of bioactive material by obstructing the pores of the interior core.

13. The suture or scaffold of claim 12, wherein said exterior surface further comprises a layer of biodegradable material that retains said particulate in material within the pores of said interior core.

14. The suture or scaffold of claim 1, wherein said interior core comprises a porous structure.

15. The suture or scaffold of claim 1, wherein said interior core comprises a woven structure.

16. The suture or scaffold of claim 1, wherein said interior core comprises a plurality of filaments.

17. The suture or scaffold of claim 16, wherein one or more of said filaments is fabricated of a material that binds said bioactive material.

18. The suture or scaffold of claim 1, wherein said interior core binds, absorbs, adsorbs, or otherwise immobilizes said bioactive material.

19. The suture or scaffold of claim 1, wherein said interior core entrains or entraps a separate structure that itself binds, absorbs, adsorbs, or otherwise immobilizes said bioactive material.

20. The suture or scaffold of claim 19, wherein said separate structure comprises electrospun materials, nanowires, protein-coated core fibers, block copolymers or a combination thereof.

21. The suture or scaffold of claim 1, wherein said interior core is comprised of a rolled layer of a film or tape-like material.

22. The suture or scaffold of claim 1, wherein said interior core comprises a viscous material.

23. The suture or scaffold of claim 22, wherein said viscous material is selected from the group consisting of a hydrogel, an emulsion and a foam material.

24. The surgical suture or longitudinal tissue scaffold of claim 1, wherein said exterior surface comprises one or more layers of sheathing material, further wherein said interior core and said one or more sheathing layers are of similar length when extended under tension, further wherein the proximal ends of said interior core and said one or more sheathing layers are concentrically joined.

25. The suture or scaffold of claim 24, wherein the proximal ends of said interior core and said one or more sheathing layers are joined to a suture needle while a distal portion of said interior core is free from said one or more sheathing layer.

26. The suture or scaffold of claim 24, wherein said interior core and said one or more sheathing layers are provided at their respective distal ends with coordinating stop components, said stop components mating and interlocking when said one or more sheathing layers is fully extended over an exposed interior core so as to inhibit subsequent relative motion of the two distal ends.

27. The suture or scaffold of claim 26, wherein the interlocking stop components provide a hydraulic seal that inhibits migration of said bioactive material dispersed within said interior core through the distal end thereof.

28. The suture or scaffold of claim 1, wherein said interior core includes a series of obstructions disposed at periodic intervals along its longitudinal axis, said obstructions impairing the longitudinal migration of said bioactive material.

29. The suture or scaffold of claim 1, wherein said exterior surface is constricted about said interior core at periodic intervals along the longitudinal axis so as to divide the interior core into a plurality of discrete sections, said constrictions impairing the longitudinal migration of said bioactive material from one interior section to another.

30. The suture or scaffold of claim 1, wherein said interior core further comprises a section of leader material that facilitates the longitudinal displacement of said interior core relative to said exterior sheathing layer.

31. The suture or scaffold of claim 30, wherein said leader material comprises a visual identifier that differentiates it from the remainder of said interior core, said visual identifier selected from the group consisting of a difference in color, shade, texture and pattern.

32. The suture or scaffold of claim 1, wherein a proximal or a distal end of the suture is differentiated from the remainder of said suture or scaffold by means of (a) a visual identifier selected from the group consisting of a difference in color, shade, texture and pattern, and (b) a difference in one or more physical properties selected from the group consisting of concentration of bioactive material, knot holding characteristics and handling characteristics.

33. A precursor construct capable of being assembled into the suture or scaffold of claim 1, said precursor construct comprising:

(i) a fixed length interior core capable of retaining a concentration of bioactive material, said interior core comprising a proximal portion and a distal portion; and

(ii) a woven sheath in a compressed state disposed only about the proximal portion of said interior core, leaving the distal portion of said interior core exposed, wherein said woven sheath may be converted to an extended state wherein it covers both proximal and distal portions of said interior core to inhibit migration of said bioactive material out of said interior core, further wherein the woven sheath'"'"'s compressed state length ranges from 5 to 90% of its extended state length.

34. The precursor construct of claim 33, wherein said compressed state length of said sheath ranges from 10 to 40% of its extended state length.

35. A precursor construct capable of being assembled into the suture or scaffold of claim 1, said precursor construct comprising a woven exterior sheath disposed about a filamentous interior core, wherein said sheath is partially displaced from said interior core to expose a length of said core, further wherein said interior core filaments are capable of binding, absorbing, adsorbing, or otherwise immobilizing a bioactive material and said exterior sheath is fabricated of a porous material or a material that degrades over time when in a biological environment, thereby exposing said interior core and the contents of to said biological environment.

36. A surgical suturing kit comprising a surgical suture precursor construct in a sterilizable package in combination with one or more sutures, suture needles or other medical devices, said package having plurality of discrete compartments including (i) a first compartment comprising a reservoir and an infusion port through which a bioactive material may be introduced, wherein said reservoir houses a distal portion of said precursor construct comprised of an exposed section of interior core, (ii) a second compartment housing the proximal portion of said precursor construct comprising one or more woven sheathing layers;

and (iii) an optional third compartment comprising said one or more sutures, suture needles or other medical devices.

37. A surgical suturing kit comprising a surgical suture precursor construct in a sterilizable package in combination with one or more sutures, suture needles or other medical devices, said package having plurality of discrete compartments including (i) a first compartment comprising a reservoir and an infusion port through which a bioactive material may be introduced, wherein said reservoir retains in a deformed state a distal portion of a precursor construct having an exterior surface and an interior core and comprised of a matrix of interwoven filaments or a porous monofilament, such that the interstices between interwoven filaments or the pores of the monofilament are of a first size and shape sufficient to permit the migration of bioactive material introduced into said reservoir, across said exterior surface, and into said interior core;

(ii) a transforming port through which a proximal portion of said precursor passes to form a surgical suture, wherein the port is of a design which induces said interstices or pores to take a second size and shape sufficient to restrict the migration of said bioactive material from said interior core across said exterior surface; and

(iii) an optional second compartment abutting said transforming port comprising said one or more sutures, suture needles or other medical devices.

38. A surgical suturing kit comprising a surgical suture precursor construct in a sterilizable package in combination with one or more sutures, suture needles or other medical devices, said package having plurality of discrete compartments through which said precursor construct may be serially drawn and in which said precursor construct may be exposed to two or more different materials for incorporation into the assembled suture as a series of concentric layers.

39. A method of making a surgical suture or an elongate linear tissue scaffold having an exterior surface and interior core comprised of a matrix of interwoven filaments or a porous monofilament, wherein a concentration of a bioactive material selected from the group consisting of biological cells and therapeutic agents is dispersed throughout said interior core, said method comprising the steps of:

(a) compressing or otherwise manipulating said matrix along or around a longitudinal axis so as to deform the interstices between interwoven filaments or the pores of the monofilament to a first size and shape sufficient to permit the migration of said bioactive material from a surrounding media, across said exterior surface, and into said interior core; and

(b) manipulating said bioactive material-containing matrix along or around said longitudinal axis so as to shrink said interstices or pores to a second size and shape sufficient to restrict the migration of said bioactive material from said interior core across said exterior surface.

40. A method of making a surgical suture or an elongate linear tissue scaffold having an exterior surface of woven or film construct and an interior core comprised of multiple filaments or a porous monofilament, wherein a concentration of a bioactive material selected from the group consisting of biological cells and therapeutic agents is dispersed throughout said interior core, said method comprising the steps of:

(a) providing an exposed section of said interior core without said surrounding sheath;

(b) contacting said exposed section with a media containing said bioactive material, such that said bioactive material is entrained in among said core fibers or in the pores of said core; and

(b) manipulating said core or said sheath to cause said core to be surrounded by said sheath with bioactive material present in the core.

41. A method for applying a target agent to a portion of a medical device and subsequently coating or covering the portion with additional agents or materials to yield a coated target agent-containing medical device, said method comprising the following steps:

a. providing a sterile package comprising a reservoir housing a medical device or portion thereof, at least one infusion port configured to permit the sterile introduction of at least one target agent into said reservoir, and at least one aspiration port configured to permit the sterile expulsion of at least one target agent;

b. optionally introducing a binding agent that facilitates the binding of a target agent to the medical device into said reservoir via said at least one infusion port and optionally expelling any excess binding agent from said reservoir via said at least one aspiration port;

c. introducing a target agent into the reservoir through said at least one infusion port and permitting said medical device to bind, absorb, adsorb, or otherwise immobilize said target agent;

d. expelling residual target agent from said reservoir through said at least one aspiration port;

e. optionally introducing a flushing material said reservoir to facilitate dilution and removal of excess target agent and subsequently expelling said flushing material from said reservoir through said at least one aspiration port; and

f. introducing one or more additional target agents or coating molecules into said reservoir via said at least one infusion port and permitting said medical device to bind, absorb, adsorb, or otherwise immobilize said additional target agents or coating materials.

42. A method of serially exposing a medical device to multiple target agents or materials, the method comprising the following steps:

a. providing a sterile package comprising two or more discrete compartments or zones, a first of which houses a medical device or portion thereof and includes at least one infusion port configured to permit the sterile introduction of at least one target agent into said compartment;

b. introducing a target agent into said first compartment through said at least one infusion port and permitting said medical device to bind, absorb, adsorb, or otherwise immobilize said target agent;

c. drawing the target agent-containing medical device into a second compartment and exposing said device to additional target agents or coating molecules contained therein; and

d. optionally, drawing the target agent-containing medical device into one or more additional compartments and exposing said device to one or more additional target agents or coating molecules contained therein.