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Stabilized polyglycolic acid fibre-based tubes for tissue engineering
129
The Biomaterials Silver Jubilee Compendium
Biomaterials 17 (1996) 115-124 (~) 1996 Elsevier Science Limited Printed in Great Britain. All rights reserved 0142-9612/96/$15.00
ELSEVIER
Stabilized polyglycolic acid fibrebased tubes for tissue engineering D.J. Mooney *t* C L. Mazzoni* C. Breuer* K. McNamara* D. Hern*, J.P. Vacanti* and R. Langer* 9
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~
9
9
*Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; tDepartment of Surgery, Harvard Medical School and Children's Hospital, Boston, MA 02115, USA Polyglycolic acid (PGA) fibre meshes are attractive candidates to transplant cells, but they are incapable of resisting significant compressional forces. To stabilize PGA meshes, atomized solutions of poly(L-lactic acid) (PLLA) and a 50/50 copolymer of poly(D,L-lactic-co-glycolic acid) (PLGA) dissolved in chloroform were sprayed over meshes formed into hollow tubes. The PLLA and PLGA coated the PGA fibres and physically bonded adjacent fibres. The pattern and extent of bonding was controlled by the concentration of polymer in the atomized solution and the total mass of polymer sprayed on the device. The compression resistance of devices increased with the extent of bonding, and PLLA bonded tubes resisted larger compressive forces than PLGA bonded tubes. Tubes bonded with PLLA degraded more slowly than devices bonded with PLGA. Implantation of PLLA bonded tubes into rats revealed that the devices maintained their structure during fibrovascular tissue ingrowth, resulting in the formation of a tubular structure with a central lumen. The potential of these devices to engineer specific tissues was exhibited by the finding that smooth muscle cells and endothelial cells seeded onto devices in vitro formed a tubular tissue with appropriate cell distribution.
Keywords: Tissue engineering, polyglycolic acid, polylactic acid, smooth muscle cells, endothelial cells Received 26 October 1994; accepted 5 January 1995
to engineer a variety of tissues, including liver, cartilage and intestine 3. This class of polymers degrades by a simple hydrolysis mechanism, and by varying the ratio of lactic and glycolic acids in the polymer one can control the crystallinity of the polymer, and thus its degradation rate and mechanical properties 4. Furthermore, these polymers can be processed to yield a variety of different structures, including fibres, hollow tubes and porous sponges 5-7. Non-woven meshes of polyglycolic acid (PGA) fibres have been particularly attractive materials for use as cell delivery devices as they are highly porous, permitting diffusion of nutrients throughout the device following implantation while allowing subsequent neovascularization of the developing tissue, and they can be easily fabricated into devices with varying geometry. However, this material lacks the structural stability to withstand compressive forces in vivo, and external supports are necessary if one desires to form a stable three-dimensional structure (e.g. a tube) from this material 8' 9. In this study, we investigated whether threedimensional structures capable of resisting large compressive forces and guiding the formation of a desired tissue structure could be formed from PGA fibre meshes by physically bonding adjacent fibres using a spray casting method. Poly(L-lactic acid)
While organ transplantation and tissue reconstruction are highly successful therapies for a variety of maladies, a shortage of donor tissue limits their application to a percentage of those who could potentially benefit from these therapies. For example, over 83 000 people either died or were maintained on less-thanoptimal therapies due to a lack of donated organs in the USA in 19901. To aid these people, a variety of investigators have proposed to engineer new tissues by transplanting isolated cell populations on biomaterial scaffolds to create functional new tissues in vivo 2. To engineer complex tissues such as blood vessels or intestine, cells must be localized to a specific site in vivo, and the formation of an appropriate tissue structure from the implanted cells and the host tissue must be promoted. Biodegradable materials are particularly attractive for fabricating the devices utilized ta transplant cells and engineer new tissues because they can be designed to erode after tissue development is complete, leaving a completely natural tissue 2'3. Templates synthesized from polymers of the lactic and glycolic acid family have previously been utilized tCurrent address: Departments of Biological and Materials Sciences and Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA. Correspondence to Prof. R. Longer. 115
Biomaterials 1996, Vol. 17 No. 2
The Biomaterials Silver Jubilee Compendium
Biomaterials 17 (1996) 115-124 (~) 1996 Elsevier Science Limited Printed in Great Britain. All rights reserved 0142-9612/96/$15.00
ELSEVIER
Stabilized polyglycolic acid fibrebased tubes for tissue engineering D.J. Mooney *t* C L. Mazzoni* C. Breuer* K. McNamara* D. Hern*, J.P. Vacanti* and R. Langer* 9
"
~
9
9
*Department of Chemical Engineering, Massachusetts Institute of Technology, Cambridge, MA 02139, USA; tDepartment of Surgery, Harvard Medical School and Children's Hospital, Boston, MA 02115, USA Polyglycolic acid (PGA) fibre meshes are attractive candidates to transplant cells, but they are incapable of resisting significant compressional forces. To stabilize PGA meshes, atomized solutions of poly(L-lactic acid) (PLLA) and a 50/50 copolymer of poly(D,L-lactic-co-glycolic acid) (PLGA) dissolved in chloroform were sprayed over meshes formed into hollow tubes. The PLLA and PLGA coated the PGA fibres and physically bonded adjacent fibres. The pattern and extent of bonding was controlled by the concentration of polymer in the atomized solution and the total mass of polymer sprayed on the device. The compression resistance of devices increased with the extent of bonding, and PLLA bonded tubes resisted larger compressive forces than PLGA bonded tubes. Tubes bonded with PLLA degraded more slowly than devices bonded with PLGA. Implantation of PLLA bonded tubes into rats revealed that the devices maintained their structure during fibrovascular tissue ingrowth, resulting in the formation of a tubular structure with a central lumen. The potential of these devices to engineer specific tissues was exhibited by the finding that smooth muscle cells and endothelial cells seeded onto devices in vitro formed a tubular tissue with appropriate cell distribution.
Keywords: Tissue engineering, polyglycolic acid, polylactic acid, smooth muscle cells, endothelial cells Received 26 October 1994; accepted 5 January 1995
to engineer a variety of tissues, including liver, cartilage and intestine 3. This class of polymers degrades by a simple hydrolysis mechanism, and by varying the ratio of lactic and glycolic acids in the polymer one can control the crystallinity of the polymer, and thus its degradation rate and mechanical properties 4. Furthermore, these polymers can be processed to yield a variety of different structures, including fibres, hollow tubes and porous sponges 5-7. Non-woven meshes of polyglycolic acid (PGA) fibres have been particularly attractive materials for use as cell delivery devices as they are highly porous, permitting diffusion of nutrients throughout the device following implantation while allowing subsequent neovascularization of the developing tissue, and they can be easily fabricated into devices with varying geometry. However, this material lacks the structural stability to withstand compressive forces in vivo, and external supports are necessary if one desires to form a stable three-dimensional structure (e.g. a tube) from this material 8' 9. In this study, we investigated whether threedimensional structures capable of resisting large compressive forces and guiding the formation of a desired tissue structure could be formed from PGA fibre meshes by physically bonding adjacent fibres using a spray casting method. Poly(L-lactic acid)
While organ transplantation and tissue reconstruction are highly successful therapies for a variety of maladies, a shortage of donor tissue limits their application to a percentage of those who could potentially benefit from these therapies. For example, over 83 000 people either died or were maintained on less-thanoptimal therapies due to a lack of donated organs in the USA in 19901. To aid these people, a variety of investigators have proposed to engineer new tissues by transplanting isolated cell populations on biomaterial scaffolds to create functional new tissues in vivo 2. To engineer complex tissues such as blood vessels or intestine, cells must be localized to a specific site in vivo, and the formation of an appropriate tissue structure from the implanted cells and the host tissue must be promoted. Biodegradable materials are particularly attractive for fabricating the devices utilized ta transplant cells and engineer new tissues because they can be designed to erode after tissue development is complete, leaving a completely natural tissue 2'3. Templates synthesized from polymers of the lactic and glycolic acid family have previously been utilized tCurrent address: Departments of Biological and Materials Sciences and Chemical Engineering, University of Michigan, Ann Arbor, MI 48109, USA. Correspondence to Prof. R. Longer. 115
Biomaterials 1996, Vol. 17 No. 2