referring to fig1 a - 1c , some of the drawbacks of previously known bioactive agent delivery systems are described . fig1 a illustrates a previously known injection needle 10 being brought into approximation with tissue mass t . once the tip of needle 10 is inserted into the tissue , as shown in fig1 b , bioactive agent b , which may comprise stem cells , is injected into the tissue mass . applicant has discovered that pressurized injection of a bioactive agent may have a substantial detrimental effect both on the agent delivered and the tissue to be treated . for example , applicant has conducted studies in which it had been observed that pressurized injection causes the injectate stream to impinge violently against the tissue as it leaves the tip of the injection needle . during injection , the injectate stream is turbulent , and may experience rapid localized pressure fluctuations . these effects may damage the bioactive agent , particularly where the agent comprises stem cells , by rupturing the cell membrane or injuring the cellular components . in addition , as illustrated in fig1 c , once needle 10 has been withdrawn from the needle track n , the potential exists for the injected bioactive agent b to be expelled from the needle track , with concomitant risk of embolization . applicant has concluded that a higher yield of viable cells may be delivered to a target tissue if apparatus and methods could be provided that reduce the effects of pressurized injection , including lysis and expulsion . referring now to fig2 a to 2c , apparatus and methods of the present invention are described that overcome the drawbacks of previously known systems for delivering fragile bioactive agents , such as stem cells . as shown in fig2 a , in accordance with the principles of the present invention , needle 20 is first approximated to spinal cord tissue mass t . in fig2 b , needle 20 is shown inserted into the tissue mass . in fig2 c , as needle 20 is withdrawn from the tissue mass , bioactive agent b is delivered from the tip of the needle and deposited in the needle track . in accordance with the principles of the present invention , the bioactive agent is injected into the tissue under little pressure and with substantially less turbulence and localized pressure fluctuation than in previously known injection systems . also , the bioactive agent will not damage the tissue mass by splitting the tissue along naturally - occurring striations . these benefits of atraumatic injection may be particularly advantageous in the repair of an injured or severed spinal cord . in fig3 a and 3b , apparatus constructed in accordance with the principles of the present invention is described , in which distal end 25 includes selectively extendable needles 26 . as depicted in the figures , needles 26 are configured to flare outward when extended beyond distal end 25 of the apparatus , thereby enhancing dispersal of the bioactive agent into tissue mass t . as described above for the embodiment of fig2 , needles 26 are configured to delivery bioactive agent b into the tissue mass while minimizing barotrauma to the bioactive agent and the injury to the tissue mass . although distal end 25 illustratively includes three needles 26 , a greater or lesser number of needles may be employed without departing from the spirit of the present invention . referring now to fig4 a and 4b , apparatus constructed in accordance with the principles of the present invention is described . apparatus 30 comprises handle 31 that is configured to accept conventional syringe 28 , which may be loaded with a preselected bioactive agent , such as stem cells in a nutrient solution . the barrel of syringe 28 is removably coupled to tube 32 via fluid - tight seal 33 . tube 32 , which carries one or more tissue - piercing needles at its distal end , is arranged to reciprocate through sleeve 34 so that the distal tip of the needle extends beyond bushing 35 when the device is actuated . piston 29 of syringe 28 is removably coupled to block 36 and rails 37 . handle 31 includes trigger 38 that may be depressed to selectively actuate apparatus 30 . in particular , trigger 38 is coupled to tube 33 via gear train 39 and linkage 40 . clamp 41 is configured to grip and reciprocate the body of the syringe in accordance with the degree of actuation of trigger 38 . each of rails 37 preferably includes a portion that forms a rack to permit forward movement of piston 29 of the syringe during a first range of motion of trigger 38 , and then retain piston 29 stationary relative to rails 37 during a second range of motion of the trigger . link 40 is coupled to clamp 41 so that , after syringe 28 and piston 29 are advanced during the initial range of motion of the trigger , the piston is held stationary while clamp 41 retracts tube 32 and needles from the needle track ( s ) and simultaneously urges the body of syringe 28 proximally . this motion causes the bioactive material within syringe 28 to be dispensed into the needle track ( s ) ( see fig2 and 3 ) at low velocity and with little or no barotrauma . as depicted in fig4 b ( but omitted elsewhere for clarity ), trigger 38 and link 40 preferably are biased by springs 42 and 43 , respectively , to return the mechanism to its starting position when trigger 38 is released . referring now also to fig5 a - 5c , operation of apparatus 30 is described . in fig5 a , trigger 38 of the apparatus is shown at its initial position , and with syringe 28 and piston 29 in the proximal - most positions . as shown in fig5 b , as the trigger 38 is depressed about half - way through its range of motion , gear train 39 and link 40 urge syringe 28 , piston 29 and rails 37 in the distal direction in unison . this in turn causes tube 32 and clamp 41 to be advanced distally , in turn causing needles 43 to extend beyond bushing 35 . illustratively , the tissue - piercing end of tube 33 includes three needles 43 that flare outward upon entering into a tissue mass , as depicted in fig3 a . because syringe 28 and piston 29 are moved in unison , the bioactive agent contained within syringe 28 is subjected to substantially no hydraulic forces , and the distance between block 36 and the proximal - most portion of syringe 28 remains unchanged . as further depicted in fig5 c , continued depression of trigger 38 causes link 40 to begin retracting tube 32 in the proximal direction . this motion also drives clamp 41 in the proximal direction . because the rack portions of rails 37 disengage from link 40 and gear train 39 during proximal movement of clamp 41 , rails 37 and piston 29 remain stationary . consequently , proximal movement of clamp 41 and tube 32 both retracts needles 43 from the needle tracks formed in the tissue , and urges the body of syringe 28 against piston 29 . still referring to fig5 c , proximal translation of clamp 41 also causes the distance between block 36 and the proximal - most portion of syringe 28 to shorten . this action applies sufficient pressure to the contents of syringe 28 to dispense the bioactive agent into the needle tracks formed by needles 43 as the needles withdraw from the tissue . when the clinician releases trigger 38 , springs 42 and 43 return tube 32 and clamp 41 to the starting position , shown in fig5 a . apparatus 30 then may be repositioned , and the above process repeated . as will be appreciated , the volume of injected material delivered into the target tissue may be adjusted depending upon the target tissue milieu . for example , for tissue or muscle that is fairly elastic , such as heart muscle , additional material may be injected to create low - pressure compartments within the tissue . on the other hand , lower volumes may be employed in less resilient structures , such as the spinal cord and brain . with respect to fig6 a and 6b , in accordance with another aspect of the invention , needles 43 ′ of apparatus 30 may have different predetermined lengths so as to deliver the bioactive agent at various depths within spinal cord s to treat injured region d . as illustrated in fig6 a , needles 43 ′ may first be used to deliver bioactive agent on a first side of a severed region d of spinal cord s , and then moved and applied to the opposite side of the severed region ( shown in dotted line in fig6 a ). additionally , needles 43 ′ may be arranged to be individually rotated so that the bioactive agent is dispersed in preselected directions . fig6 b depicts the use of grid 50 to guide needles 43 ′ into predetermined locations along spinal cord s . grid 50 comprises block 51 having a plurality of through holes 52 disposed along its surface to provide a predetermined separation between injection regions . advantageously , grid 50 lends structural support to damaged spinal region d during stem cell injection . as in the method depicted in fig6 a , apparatus 30 may be used to inject needles 43 ′ at a first location , and then repositioned using grid 50 ( as shown in dotted line ) to provide subsequent injections . with further reference to fig6 , according to some methods of the present invention , a predetermined amount of cerebrospinal fluid may be removed from spinal cord s prior to injecting the bioactive agent . preferably , the amount of cerebrospinal fluid removed is substantially equivalent to the amount of bioactive agent , e . g ., stem cell solution , injected into the spinal cord . this step of the method is expected to enhance atraumatic delivery of the bioactive agent by reducing the risk that the injection prevents injury to the spinal artery or surrounding delicate tissue during injection . referring now to fig7 a and 7b , an alternative embodiment of an injection needle constructed in accordance with the principles of the present invention is described . needle 60 comprises a glass or polymer microfiber adapted to receive and transmit electric signals , and includes tissue - piercing distal end 61 and interior lumen 62 . needle 60 is loaded with a bioactive agent , preferably comprising stem cells 65 , and in addition is coupled to power supply 63 that applies an electric field longitudinally along needle 60 . when energized by power supply 63 , an electric field is applied to needle 60 that attracts negatively charged stem cells 65 toward end 61 , where they are deposited into the spinal cord . in particular , as depicted in fig7 b , a positive charge is induced at distal end 61 of needle 60 , thereby causing negatively charged stem cells 65 to be drawn to the distal tip of the needle . stem cells 95 are believed to be negatively charged in the natural state , so that they are drawn toward the positive charge at distal end 61 of needle 60 . alternatively , an ionic solution containing negatively charged particles may be added to the bioactive agent prior to injection to increase the attraction of the stem cells towards a positive charge . the movement of stem cells 65 toward the positive charge causes a predetermined amount of the stem cells to be ejected from distal end 61 into a target tissue mass , such as a damaged region of spinal cord . needle 60 optionally may transmit a signal that defines a location of the needle when viewed using an mri or ct device . referring now to fig8 a and 8b , another alternative embodiment of the present invention is described . needle 70 comprises an electroactive polymer that forms an actuator , and includes tissue - piercing distal end 71 and interior lumen 72 . needle 70 is loaded with a bioactive agent , preferably comprising stem cells 75 , and is coupled to power supply 73 that applies an electric field longitudinally along needle 70 . electroactive polymers are members of the family of plastics referred to as “ conducting polymers ,” and are preferred for the practice of the present invention due to their small size , large force and strain and low cost . in fig8 , injection needle 70 comprises an electroactive polymer that is adapted to contract in response to electrical stimulation . suitable electroactive polymers include , but are not limited to , polypyrrole , polyacetylene , polyaniline and polysulfone . oxidation or reduction of these polymers leads to a charge imbalance that results in a flow of ions ( dopants ) into the material in order to balance charge . the ions enter the polymer from an ionically conductive electrolyte medium that is coupled to the polymer surface . conversely , if ions are already present in the polymer when it is oxidized or reduced , they may exit the polymer . dimensional changes in electroactive polymers may be triggered by the mass transfer of ions into or out of the polymer . for some electroactive polymers , the expansion is due to ion insertion between chains , whereas repulsion between chains is the dominant effect for other electroactive polymers . the mass transfer of ions into and out of the electroactive polymer leads to an expansion or contraction of the polymer . in this manner , needle 70 may be contracted such that a predetermined amount of bioactive agent is ejected from distal end 71 of the needle . more specifically , needle 70 comprises an electroactive polymer that is configured to contract when an electric charge is applied to the needle by power supply 73 . needle 70 has a first diameter ( fig8 a ) and a second , contracted diameter ( fig8 b ) when energized . referring to fig8 b , when an electrostatic charge is applied to injection needle 70 , the needle contracts and the diameter of lumen 72 decreases , thereby expelling a predetermined amount of stem cells 75 out of distal end 71 of needle 70 . it is expected that constriction of lumen 72 is a bulk phenomenon that imposes a low - level distributed compressive force to the bioactive agent disposed in the lumen . accordingly , substantially smaller local pressure fluctations will be imposed on the bioactive agent as compared to pressurized injection using a syringe , thereby reducing barotrauma and leading to substantially better viability of the implanted stem cells . as will of course be understood , the embodiments of fig7 and 8 may include multiple needle tips to deliver bioactive agent at several sites or depths simultaneously , and may be used with a grid , such as described with respect to fig6 , to deliver the bioactive agent according to a predetermined pattern . as will further be understood , power supplies 63 and 73 of the embodiments of fig7 and 8 , respectively , may include controllers that control operation of the electric fields applied to the needles so that predetermined amounts of bioactive agent are delivered by the needles when activated . while preferred illustrative embodiments of the invention are described above , it will be apparent to one skilled in the art that various changes and modifications may be made therein without departing from the invention . the appended claims are intended to cover all such changes and modifications that fall within the true spirit and scope of the invention .
methods and apparatus are provided for treating damaged tissue using apparatus that atraumatically delivers a bioactive agent within the tissue , wherein the apparatus provides a column of stem cells may be advanced simultaneously with a needle during needle insertion , and then held stationary or injected at low pressure while retracting the needle . alternatively , the needle may employ electromotive forces , or to change a dimension of the needle , to expel the bioactive agent into the needle track .