Method and matrix for brain tissue repair

Abstract

Described is a method of repairing the parenchyma of the brain. The method comprises implanting a biodegradable porous polymeric matrix block, such as a piece of collagen matrix, to a void in the brain through a tubular device. A medical device for use in the method is also described.

Description

Attorney Docket No. ILS064PCTMETHOD AND MATRIX FOR BRAIN TISSUE REPAIRTECHNICAL FIELD

[0001] The present disclosure relates generally to tissue regeneration and more specifically, to methods and medical devices for repairing or regenerating tissue in the central nervous system.BACKGROUND

[0002] The chordate nervous system is divided into the central nervous system (CNS) and the peripheral nervous system (PNS). The CNS includes the brain and spinal cord. The brain is an essential and complex organ that controls many body functions, such as memory, motor skills, breathing, and many other processes that regulate the body. The parenchyma of the brain (or brain parenchyma) refers to the functional tissue in the brain that is made up of brain cells including neurons and glial cells. Neurons generate and receive electrical and chemical signals, and glial cells modulate neuron function and connectivity. Damage or trauma to the brain parenchyma could results in a loss of cognitive ability, motor and / or sensory functions, or even death. The brain and spinal cord are enveloped in layers of protective connective tissues known collectively as the meninges. The inner layer that is in intimate contact with the parenchyma is the pia (or pia mater). The middle layer is the arachnoid (or arachnoid mater). The tough outer layer is the dura (or dura mater). The meninges separate the CNS from their bony surroundings and the rest of the body and provide a substantial portion of the blood brain barrier. More specifically, the meninges separate the brain from the skull and separate the spinal cord from vertebral column. The meninges together with cerebrospinal fluid provide mechanical protection and cushioning of the brain from external mechanical forces. Direct physical access to the internal structures of the brain requires passage through the meninges and they are routinely sectioned to allow access to the parenchyma. Access to the parenchyma and internal structures of the brain may be required to remove tumors, repair blood vessels, remove blood clots, remove bone and tissue fragments, remove foreign objects, or provide access for intracranial drainage catheters or electrodes.

[0003] Treatment for a brain tumor depends on various factors, including, for example, whether the tumor is cancerous or benign and the size and location of the brain tumor.Attorney Docket No. ILS064PCTSurgery is one of the treatment options for brain tumors. The surgery option may include a complete or partial resection and removal of the brain tumor depending on the location of the tumor in the brain, with a goal to remove as much of the tumor as possible without damaging critical healthy brain tissue.

[0004] Types of brain tumor surgery include traditional open surgery (craniotomy) and minimally invasive surgery (MIS). A craniotomy is a procedure that involves removal of a piece of bone from the skull to expose the brain and provide the surgeon access to remove the tumor.

[0005] Endoscopic brain surgery is a minimally invasive surgical procedure in which the surgeon places an endoscope, which typically includes a long, thin tube equipped with lights and cameras, through a small hole on the skull and advance it through the brain tissue until it reaches the brain tumor, and then the surgeon puts one or more surgical tools through the tube to remove the tumor. Another minimally invasive surgical procedure involves the use of a tubular retractor system, in which procedure the surgeon makes a small incision in the scalp and a small opening in the skull, and with the assistance of computerized navigation, moves the tubular retractor to displace and hold apart tissue to allow the surgeon to reach a particular area of the brain where surgical intervention is needed.

[0006] Medical devices for MIS procedures are described or available on the market. For example, U.S. Patent No. 10,105,042 describes a cannula with proximally amounted camera for accessing a predetermined area in the brain.

[0007] A resection cavity is the space or void that remains in the parenchyma of the brain after a tumor is surgically removed from the patient. During or shortly after a brain surgery, a resection cavity is often filled with cerebrospinal fluid and blood. Resection cavities left in the patient may eventually shrink and collapse, but some may stay the same size for a long period of time or leave a permanent void in the brain. A glial scar formation may occur after injury to the central nervous system (CNS), such as surgically induced injury to the parenchyma of the brain. Glial scarring is a hypertrophic tissue response of the parenchyma to mechanical and physiological injuries. It can be a highly destructive process that may extend tissue damage far beyond the initial zone of injury. In addition to causing a necrotic cascade in the neural elements of the parenchyma, the composition of the glial scar extracellular matrix is known to hinder axonal extensions and prevent neuronal reconnectionAttorney Docket No. ILS064PCT and thus, impede functional repair of damaged CNS. There is currently no clinically proven method of repairing or regenerating brain parenchyma.

[0008] Therefore, there remains a need for methods and devices that provide effective treatment with minimized additional parenchymal injury to patients in need of repair of brain injuries whether they were surgically induced, caused by trauma or otherwise.SUMMARY

[0009] The present disclosure generally relates to methods for treating wounds or injuries in the central nervous system, and devices for performing such methods.

[0010] In an aspect of the present disclosure, a method of treating a wound in the brain, including a surgically induced brain injury, traumatic brain injury, a void inside the parenchyma of the brain, or a condition in need of healing or regeneration of the parenchyma of the brain, is provided. The method comprises: providing an elongated hollow tubular body having a proximal end and a distal end and a lumen extending from the proximal end to the distal end; providing a plunger comprising a shaft having a proximal end and a distal end and a plunger body located at the distal end of the shaft, the plunger body being insertable through the proximal end of the tubular body and slidably movable within the lumen of the tubular body; providing a biodegradable porous polymeric matrix block configured to fill at least a portion of the length of the hollow tubular body, wherein the biodegradable porous polymeric matrix block has a dimension smaller than the inner diameter of the tubular body, and a length shorter than the length of the tubular body; inserting the biodegradable porous polymeric matrix block into the tubular body; inserting the plunger into the tubular body until the plunger body is positioned near or in contact with the biodegradable porous polymeric matrix block; advancing the tubular body towards the wound; moving the plunger body and / or the tubular body whereby the plunger body and the tubular body are slid relative to each other generally coaxially allowing the biodegradable porous polymeric matrix block to move distally relative to the tubular body until it exits the distal end of the tubular body; and retracting the tubular body and plunger out of the patient.

[0011] The method may be used for treating a surgically induced brain injury, brain trauma, a void inside the parenchyma of the brain, or a condition in need of healing or regeneration of the parenchyma of the brain.Attorney Docket No. ILS064PCT

[0012] The biodegradable porous polymeric matrix block used in the method may be a collagen matrix block, which is an integral piece of collagen matrix or formed by combining a plurality of collagen matrix pieces, for example, a cylindrical body of collagen matrix or a rolled-up or folded sheet of collagen matrix, or stacked strips of collagen matrix. The collagen matrix provides the benefit of a wound healing process inside the parenchyma of the brain, and reduction or disappearance of a void inside the brain.

[0013] In another aspect of the present disclosure, a medical device is provided which comprises: an elongated hollow tubular body having a proximal end, a distal end and a lumen extending from the proximal end to the distal end, an inner diameter, and a length; a biodegradable porous polymeric matrix block configured to fill at least a portion of the length of the hollow tubular body, wherein the biodegradable porous polymeric matrix block has a dimension smaller than the inner diameter of the tubular body, and a length shorter than the length of the tubular body; and a plunger comprising a shaft, a handle at the proximal end of the shaft, and a plunger body located at the distal end of the shaft, wherein the plunger body has an outer diameter smaller than the inner diameter of the tubular body such that the plunger body is insertable through the proximal end of the tubular body and slidably movable within the lumen of the tubular body to advance the biodegradable porous polymeric matrix block to exit the distal end of the tubular body. In the medical device, the elongated tubular body and the biodegradable porous polymeric matrix block can be separate items and to be combined prior to use or during use by the user, or the elongated tubular body may be prefilled with the biodegradable porous polymeric matrix block.

[0014] These and other features and advantages of the invention or certain embodiments of the invention will become more apparent from the following disclosure and description of exemplary embodiments.BRIEF DESCRIPTION OF THE DRAWINGS

[0015] Embodiments of the present invention are described herein with reference to the following figures:

[0016] FIG. 1 illustrates the head of a patient with an area requiring tissue repair.

[0017] FIG. 2 illustrates a medical device for treating brain injury.Attorney Docket No. ILS064PCTDETAILED DESCRIPTION

[0018] The present disclosure provides a method of treating a condition of the brain of a mammalian subject in need of such treatment. The condition to be treated includes wounds or injuries in the parenchyma of the CNS, for example, a surgically induced brain injury, traumatic brain injury, a void inside the parenchyma of the brain, or other conditions in need of repairing, healing or regeneration of the parenchyma of the brain. Traumatic brain injury includes one caused by a gunshot or other external forces. The cerebral parenchyma loss or injury may result in a wound site that includes a void space like a tract or pocket and may be irregularly shaped.

[0019] FIG. 1 illustrates a patient 1 with an injury site or void 2 in the brain 3. A medical device 10 has been inserted into the brain with the distal end of the tubular body near or in the void 2.

[0020] FIG. 2 further illustrates medical device 10, which comprises an elongated hollow tubular body 12, a plunger 14, and a biodegradable porous polymeric matrix block 18. The plunger 14 comprises a shaft 13, a handle 15 at the proximal end of the shaft, and a plunger body 15 located at the distal end of the shaft 13. The handle is optional.

[0021] The hollow tubular body 12 has a proximal end and a distal end and a lumen extending from the proximal end to the distal end, and an inner surface 11. A hollow tubular body may be a cannula, needle, catheter, trocar, tubular retractors or the like. The tubular body may have an inner diameter bigger than 2 mm, for example, 5 mm, 10 mm, 12 mm, 15 mm, 20 mm, or more, etc.

[0022] The plunger body 15 has an outer diameter smaller than the inner diameter of the tubular body such that the plunger body is insertable through the proximal end of the tubular body and slidably movable within the lumen of the tubular body. The biodegradable porous polymeric matrix block 18 is configured to fill at least a portion of the length of the tubular body 12. In an embodiment, the dimension of the biodegradable porous polymeric block is smaller than the inner diameter of the tubular body and its length is shorter than the length of the tubular body. The biodegradable porous polymeric matrix block before it is placed within the elongated tubular body may not be dimensioned smaller than the tubular body, but the block may have some flexibility that allows it to be compressed to have a dimension smaller than the inner diameter of the tubular body, or be squeezed into the tubular body.Attorney Docket No. ILS064PCTThe plunger 14 assists the advancement of the biodegradable porous polymeric matrix block 18 to exit the distal end of the tubular body 12. A plunger may be a stylet, a device having a shaft and a plunger body with or without a handle, or a cylindrical element slidable within the tubular body. The shaft and the plunger body may be an integral piece without visible difference in their diameters or other dimensions.

[0023] The biodegradable porous polymeric matrix block 18 comprises a biodegradable porous polymeric material. Biodegradable porous polymeric matrices include porous matrices of natural fibers, porous matrices of absorbable synthetic fibers, porous composite matrices of natural and synthetic fibers, and decellularized animal tissue. Examples include collagen matrices and collagen-glycosaminoglycan matrices. The biodegradable porous polymeric matrix block is sized to fit in the elongated hollow tubular body and may stay in the tubular body with friction against the inner wall of the tubular body. For example, the biodegradable porous polymeric matrix block may be a cylinder of collagen matrix having a diameter of about 15 mm or a little smaller for use with a tubular body having an inner diameter of about 15 mm.

[0024] Biodegradable porous polymeric matrix blocks are described further using collagen matrix blocks as examples. A collagen matrix block may be an integral piece of collagen matrix or it may be formed by combining a plurality of collagen matrix pieces. Examples of integral pieces of collagen matrix include collagen matrix blocks which are cylindrical or in other shapes which are slidable within the tubular body. Other examples include a rolled-up sheet of collagen matrix or a folded sheet of collagen matrix. Collagen matrix blocks can also be combinations of collagen matrix pieces, for example, include stacked strips of collagen matrix, compressed collagen pieces or particulates, or other forms that are not flowable.

[0025] When loaded into the tubular body, the collagen matrix block preferably occupies the entire cross-section of the inner lumen thereby preventing any coring of tissue when inserting the device into the brain. The collagen matrix block also preferably occupies most or the entire volume of the inner lumen. Such configurations help prevent coring of tissue and also enhance resistance to prevent vertical compression of the collagen matrix during the implant procedure.

[0026] Collagen is a major protein component of bone, cartilage, skin, and connective tissue in animals. Collagen occurs in several types, having differing physical properties. The mostAtorney Docket No. ILS064PCT abundant types are Types I, II and III. Collagen derived from any source is suitable for use in the compositions of the present invention, including insoluble collagen, collagen soluble in acid, in neutral or basic aqueous solutions, as well as those collagens that are commercially available. Typical animal sources for collagen include, but are not limited to, recombinant collagen, fibrillar collagen from bovine, porcine, ovine, caprine and avian sources as well as soluble collagen from sources such as cattle bones and rat tail tendon. Plant derived human recombinant collagens are also available.

[0027] Examples of collagen devices and their uses in tissue regeneration have been described in U.S. Patent Nos. 5,997,895 and 8,846,060, which are incorporated herein by reference. A sheet of collagen matrix may be produced from a process comprising the steps of preparing a dispersion of collagen, lyophilizing the collagen dispersion to dryness, and then optionally cross-linking the lyophilized collagen, for example, by a glutaraldehyde solution or formaldehyde vapor.

[0028] Processes of making biodegradable matrices are described in more detail. A sheet of collagen matrix or collagen-glycosaminoglycan matrix may be produced from a process comprising the steps: (1) preparing a dispersion of collagen (for example, bovine tendon collagen); (2) optionally adding glycosaminoglycan (GAG) to the collagen dispersion; (3) lyophilizing the collagen or collagen / GAG dispersion to dryness; (4) optionally cross-linking the lyophilized collagen or collagen / GAG material; (6) optionally cutting the tissue into desired shapes and sizes; and (7) optionally sterilizing. The average pore size of the collagen matrix is within the range of about 100 pm to about 600 pm, preferably about 20 pm to 200 pm, as calculated by stereology from scanning electron micrograph of the surface or internal cross section as described by Dagalakis et al. J. of Biomedical Materials Research 14:511 (1980).

[0029] The terms “matrix” and “scaffold” as used herein refer to a construct of natural or synthetic porous polymeric materials which can be used in vivo and in vitro as structural supports for cells and tissues, frameworks for tissue formation and regeneration, or surfaces for cell contact and cell migration.

[0030] To use medical device 10 to treat a wound in the brain, insert the biodegradable porous polymeric matrix block 18 into the tubular body 12. Then insert the plunger into the tubular body until the plunger body 15 is positioned near or in contact with the biodegradable porous polymeric matrix block 18. Move the plunger body 15 and / or the tubular body 12Attorney Docket No. ILS064PCT whereby the plunger body 15 and the tubular body 12 are slid relative to each other coaxially allowing the biodegradable porous polymeric matrix block 18 to advance distally in the tubular body 12 until it exits the distal end of the tubular body. Then retract the tubular body 12 and plunger 14 out of the patient. For example, the surgeon may insert a collagen matrix block into the tubular body, insert the plunger into the tubular body until it reach or meets the collagen matrix block, insert the tubular body into the brain to a desired depth, hold the plunger in place while removing the tubular body from the brain, leaving the collagen matrix block in place, and then finally, remove the plunger. Alternatively, the surgeon may insert the tubular body into the patient’s brain first, and then insert the collagen matrix block, which may be hydrated by saline or patient’s bodily fluid, such as blood. Alternatively, once the collagen matrix is placed within the tubular body, the surgeon may advance the tubular body to a location near the wound site and hold it in place, and then move the plunger distally to push the collagen matrix block out of the tubular body.

[0031] The effects of collagen matrix implantation on the surrounding brain parenchyma over time and the effects of the brain parenchyma environment on the collagen matrix implant over time were evaluated. The results suggests that the collagen matrix itself may exert protective, anti-inflammatory, and / or pro-regenerative effects. With the use of the method and device of the present disclosure, the wound site within the brain parenchyma likely will have less blood, lower microglial infiltration into the site, less glial scarring, and / or inflammatory angiogenesis. Brain parenchyma wound site will likely have no void space or cerebrospinal fluid pocket after using the method of treatment or medical device in accordance with the present invention. The wound sites implanted with the collagen matrix block would likely be replaced with regenerated brain tissue, with a general reduction in the extent of the zone of injury in the surrounding parenchyma.

[0032] Although the invention is described herein in more detail with examples of collagen materials, the invention can also be applied to other biocompatible materials, including synthetic or natural polymers, such as water soluble polyamine materials or extracellular matrices, other macromolecules. Examples include glycosaminoglycans such as hyaluronans, chondroitin sulfate, dermatan sulfate, heparin sulfate, keratin sulfate, proteoglycans such as aggrecan, decorin, syndecans, as well as elastin, fibronectin, laminin- 1 and laminin-2.Attorney Docket No. ILS064PCT

[0033] A biodegradable porous polymeric matrix block, for example, a collagen matrix block, used in the method of the present disclosure may further carry one or more drugs, including small or large molecules or other bioactive agents for targeted release at a predetermined location in the parenchyma of the CNS. Examples of suitable drugs include, but are not limited to, antimicrobial agents, protein and peptide preparations, antipyretic, antiphlogistic and analgesic agents, anti-inflammatory agents, vasodilators, antihypertensive and anti arrhythmic agents, hypotensive agents, antitussive agents, antineoplastic agents, local anesthetics, nerve growth factors, hormone preparations, antiasthmatic and antiallergic agents, antihistaminics, anticoagulants, antispasmodics, cerebral circulation and metabolism improvers, antidepressant and antianxiety agents, vitamin D preparations, hypoglycemic agents, antiulcer agents, hypnotics, antibiotics, antifungal agents, sedative agents, bronchodilator agents, antiviral agents, dysuric agents, glycosaminoglycans, carbohydrates, nucleic acids, inorganic and organic biologically active compounds, combinations thereof, and the like. Specific biologically active agents include, but are not limited to, enzymes, angiogenic agents, anti-angiogenic agents, growth factors, antibodies, neurotransmitters, psychoactive drugs, antitumor or anticancer drugs, antimicrobial agents including antibiotics such as rifampin, chemotherapeutic drugs, drugs affecting reproductive organs, genes, oligonucleotides, combinations thereof, and the like. Other examples include macromolecules such as NGF, BDNF, CNTF, VEGF, EGF and PDGF-bb.EXAMPLES

[0034] The following examples are provided for illustrative purposes only and are in no way intended to limit the scope of the present invention.

[0035] Example 1. Collagen Matrix Block

[0036] Collagen matrices for promoting meningeal tissue growth that include collagen are described in U.S. Patent No. 5,997,895. Commercially available resorbable collagen matrix products include the DURAGEN® family of dural grafts (Integra LifeSciences, Princeton, N.J.), which are dural regeneration collagen scaffolds to be used as an onlay graft for closing the dura after surgery to prevent cerebrospinal fluid leakage. Such collagen matrix sheet when hydrated, is conformable and contours to the complex surface of the underlying patient anatomy.

[0037] Collagen matrix sheets were cut into strips at 1 mm wide x 1-2 mm high x 15 mm long.Attorney Docket No. ILS064PCTThe collagen matrix strips were then stacked and compressed to form a collagen matrix block.

[0038] Example 2. Loading Collagen Matrix Block into Hollow Tubular Body

[0039] An IV needle was loaded with the collagen matrix block prepared from Example 1. A stylet was inserted into an end of the needle until it is in contact with the collagen matrix block within the needle lumen. The steps were repeated to prepare multiple needles loaded with collagen matrix blocks.

[0040] Example 3. Implantation

[0041] Healthy pig brains were used to assess imaging and histological impacts of collagen implantation. Burr holes were made with a hand drill. With the assistance of a stereotactic system, the needle loaded with a collagen matrix block was inserted into the parenchyma of the pig’s brain. The stylet was then held in place by a pusher arm and the needle was withdrawn back over the stylet until the 15 mm collagen matrix block was in the tissue. The entire needle and stylet device was withdrawn. A regenerative collagen scaffold was placed and implanted in the parenchyma of the brain. Repeat the same process for additional implant sites and for control sites where no collagen matrix block was implanted. All bunholes were cleaned and then skin was sutured for closure.

[0042] Example 4. Histology

[0043] The pigs were euthanized several weeks after the procedures. The brains were extracted and prepared for histological assessment. The control tract had visibly more blood, much higher microglial infiltration into the site, and more glial scarring. Much greater inflammatory angiogenesis was also observed in the control tract. It was observed that a void space or a cerebrospinal fluid pocket was formed in a control tract at 9 weeks. The sites implanted with the collagen matrix block had little to no inflammation or blood and were almost completely gone at 9 weeks, without any sign of damage in the surrounding area.

[0044] As used in the specification and claim for the purposes of describing and defining the invention, the terms "about" and "substantially" represent the inherent degree of uncertaintyAttorney Docket No. ILS064PCT attributed to any quantitative comparison, value, measurement, or other representation. The terms "about" and "substantially" also represent the degree by which a quantitative representation may vary from a stated reference without resulting in a change in the basic function of the subject matter at issue. "Comprise", "include", “have,” and variations of each word include the listed parts and can include additional parts not listed. "And / or" includes one or more of the listed parts and combinations of the listed parts.

[0045] One skilled in the art will realize the disclosure may embody other specific forms without departing from the spirit or essential characteristics thereof. The foregoing examples in all respects illustrate rather than limit the disclosure described herein. The appended claims, rather than the foregoing description, thus indicate the scope of the disclosure, and embrace all changes that come within the meaning and range of equivalency of the claims.

Claims

Attorney Docket No. ILS064PCTCLAIMS1. A method of treating a wound in the parenchyma of the central nervous system of a mammalian subject, the method comprising: providing a hollow tubular body having a proximal end and a distal end and a lumen extending from the proximal end to the distal end; providing a plunger comprising a shaft having a proximal end and a distal end and a plunger body located at the distal end of the shaft, the plunger body being insertable through the proximal end of the tubular body and slidably movable within the lumen of the tubular body; providing a biodegradable porous polymeric matrix block configured to fill at least a portion of the hollow tubular body; advancing the tubular body towards the wound; inserting the biodegradable porous polymeric matrix block into the tubular body; inserting the plunger into the tubular body until the plunger body is positioned near or in contact with the biodegradable porous polymeric matrix block; moving the plunger body and / or the tubular body whereby the plunger body and the tubular body are slid coaxially relative to each other allowing the biodegradable porous polymeric matrix block to move distally relative to the tubular body until it exits the distal end of the tubular body; and retracting the tubular body and plunger out of the patient.

2. The method of claim 1, wherein the wound is a surgically induced brain injury, traumatic brain injury, a void inside the parenchyma of the brain, or a condition in need of healing or regeneration of the parenchyma of the brain.

3. The method of claim 1, wherein the biodegradable porous polymeric matrix block is an integral piece of polymeric matrix or formed by combining a plurality of polymeric matrix pieces.

4. The method of claim 1, wherein the biodegradable porous polymeric matrix block isAttorney Docket No. ILS064PCT selected from the group consisting of a rolled-up sheet of polymeric matrix, a folded sheet of polymeric matrix, a single piece of polymeric matrix which is cylindrical or in another shape slidable within the tubular body, stacked strips of polymeric matrix, and a combination thereof5. The method of claim 1, wherein the biodegradable porous polymeric matrix block has a dimension smaller than the inner diameter of the tubular body, and a length shorter than the length of the tubular body.

6. The method of any of claims 1-5, wherein the biodegradable porous polymeric matrix is a collagen matrix.

7. A method of treating a wound in the parenchyma of the central nervous system of a mammalian subject, the method comprising: providing a device comprising: an elongated hollow tubular body having a proximal end, a distal end and a lumen extending from the proximal end to the distal end, an inner diameter, and a length; and a biodegradable porous polymeric matrix block figured to fill at least a portion of the hollow tubular body the elongated hollow tubular body; providing a plunger comprising a shaft having a proximal end and a distal end and a plunger body located at the distal end of the shaft, the plunger body being insertable through the proximal end of the tubular body and slidably movable within the lumen of the tubular body; advancing the device towards the wound; inserting the plunger into the tubular body until the plunger body is positioned near or in contact with the biodegradable porous polymeric matrix block; moving the plunger body and / or the tubular body whereby the plunger body and the tubular body are slid coaxially relative to each other allowing the biodegradable porous polymeric matrix block to move distally relative to the tubular body until it exits the distal end of the tubular body; and retracting the tubular body and plunger out of the patient.Attorney Docket No. ILS064PCT8. The method of claim 7, wherein the wound is a surgically induced brain injury, traumatic brain injury, a void inside the parenchyma of the brain, or a condition in need of healing or regeneration of the parenchyma of the brain.

9. The method of claim 7, wherein the biodegradable porous polymeric matrix block is an integral piece of polymeric matrix or formed by combining a plurality of polymeric matrix pieces.

10. The method of claim 7, wherein the biodegradable porous polymeric matrix block is selected from the group consisting of a rolled-up sheet of polymeric matrix, a folded sheet of polymeric matrix, a single piece of polymeric matrix which is cylindrical or in another shape slidable within the tubular body, stacked strips of polymeric matrix, and a combination thereof.

11. The method of claim 7, wherein the device comprises the elongated tubular body and the biodegradable porous polymeric matrix block separately and to be combined prior to use, or comprises the elongated tubular body prefilled with the biodegradable porous polymeric matrix block.

12. The method of any of claims 7-11, wherein the biodegradable porous polymeric matrix is a collagen matrix.

13. A medical device comprising: an elongated hollow tubular body having a proximal end, a distal end and a lumen extending from the proximal end to the distal end, an inner diameter, and a length; a biodegradable porous polymeric matrix block configured to fill at least a portion of the length of the hollow tubular body; and a plunger comprising a shaft and a plunger body located at the distal end of the shaft, wherein the plunger body has an outer diameter smaller than the inner diameter of the tubular body such that the plunger body is insertable through the proximal end of the tubular body and slidably movable within the lumen of the tubular body to assist advancement of the biodegradable porous polymeric matrix block to exit the distal end of the tubular body.Attorney Docket No. ILS064PCT14. The medical device of claim 13, wherein the biodegradable porous polymeric matrix block is an integral piece of polymeric matrix or formed by combining a plurality of polymeric matrix pieces.

15. The medical device of claim 13, wherein the biodegradable porous polymeric matrix block is selected from the group consisting of a rolled-up sheet of polymeric matrix, a folded sheet of polymeric matrix, a single piece of polymeric matrix which is cylindrical or in another shape slidable within the tubular body, stacked strips of polymeric matrix, and a combination thereof.

16. The medical device of claim 13, wherein the biodegradable porous polymeric matrix block has a dimension smaller than the inner diameter of the tubular body, and a length shorter than the length of the tubular body.

17. The medical device of claim 13, wherein the elongated tubular body and the biodegradable porous polymeric matrix block are separate items, and the biodegradable porous polymeric matrix block is to be placed within the elongated hollow tubular body by the user.

18. The medical device of claim 13, wherein the biodegradable porous polymeric matrix block is prefilled within the elongated hollow tubular body.

19. The medical device of any of claims 13-19, wherein the biodegradable porous polymeric matrix is a collagen matrix.

20. The medical device of any of claims 13-19, which is for treating a wound in the parenchyma of the central nervous system of a mammalian subject.

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