Nerve conduits have been a viable alternative to the ‘gold standard' autograft for treating small peripheral nerve gap injuries. However, they often produce inadequate functional recovery outcomes and are ineffec...Nerve conduits have been a viable alternative to the ‘gold standard' autograft for treating small peripheral nerve gap injuries. However, they often produce inadequate functional recovery outcomes and are ineffective in large gap injuries. Ridge/groove surface micropatterning has been shown to promote neural cell orientation and guide growth. However, optimization of the ratio of ridge/groove parameters to promote orientation and extension for dorsal root ganglion(DRG) cells on poly(lactic-co-glycolic acid)(PLGA) films has not been previously conducted. Photolithography and micro-molding were used to define various combinations of ridge/groove dimensions on PLGA films. The DRG cells obtained from chicken embryos were cultured on micropatterned PLGA films for cell orientation and migration evaluation. Biodegradation of the films occurred during the test period, however, this did not cause deformation or distortion of the micropatterns. Results from the DRG cell orientation test suggest that when the ridge/groove ratio equals 1(ridge/groove width parameters are equal, i.e., 10 μm/10 μm(even)), the degree of alignment depends on the size of the ridges and grooves, when the ratio is smaller than 1(groove controlled) the alignment increases as the ridge size decreases, and when the ratio is larger than 1(ridge controlled), the alignment is reduced as the width of the grooves decreases. The migration rate and neurite extension of DRG neurons were greatest on 10 μm/10 μm and 30 μm/30 μm micropatterned PLGA films. Based on the data, the 10 μm/10 μm and 30 μm/30 μm micropatterned PLGA films are the optimized ridge/groove surface patterns for the construction of nerve repair devices.展开更多
After decades of research,peripheral nerve injury and repair still frequently results in paralysis,chronic pain and neuropathies leading to severe disability in patients.Current clinically available nerve conduits onl...After decades of research,peripheral nerve injury and repair still frequently results in paralysis,chronic pain and neuropathies leading to severe disability in patients.Current clinically available nerve conduits only provide crude guidance of regenerating axons across nerve gap without additional functionality.FK506(Tacrolimus),an FDA approved immunosuppressant,has been shown to enhance peripheral nerve regeneration but carries harsh side-effects when delivered systemically.The objective of this study was to develop and evaluate a bioresorbable drug delivery system capable of local extended delivery of FK506 that also provides topological guidance cues to guide axon growth via microgrooves.Photolithography was used to create micropatterned poly(lactide-co-glycolic acid)(PLGA) films embedded with FK506.Non-patterned,10/10 μm(ridge/groove width),and 30/30 μm patterned films loaded with 0,1,and 3 μg/cm2 FK506 were manufactured and characterized.In vitro FK506 rate of release testing indicated that the films are capable of an extended(at least 56 days),controlled,and scalable release of FK506.Neurite extension bioactivity assay indicated that FK506 released from the films(concentration of samples tested ranged between 8.46–19.7 ng/m L) maintained its neural bioactivity and promoted neurite extension similar to control FK506 dosages(10 ng/m L FK506).The multi-functional FK506 embedded,micropatterned poly(lactide-co-glycolic acid) films developed in this study have potential to be used in the construction of peripheral nerve repair devices.展开更多
文摘Nerve conduits have been a viable alternative to the ‘gold standard' autograft for treating small peripheral nerve gap injuries. However, they often produce inadequate functional recovery outcomes and are ineffective in large gap injuries. Ridge/groove surface micropatterning has been shown to promote neural cell orientation and guide growth. However, optimization of the ratio of ridge/groove parameters to promote orientation and extension for dorsal root ganglion(DRG) cells on poly(lactic-co-glycolic acid)(PLGA) films has not been previously conducted. Photolithography and micro-molding were used to define various combinations of ridge/groove dimensions on PLGA films. The DRG cells obtained from chicken embryos were cultured on micropatterned PLGA films for cell orientation and migration evaluation. Biodegradation of the films occurred during the test period, however, this did not cause deformation or distortion of the micropatterns. Results from the DRG cell orientation test suggest that when the ridge/groove ratio equals 1(ridge/groove width parameters are equal, i.e., 10 μm/10 μm(even)), the degree of alignment depends on the size of the ridges and grooves, when the ratio is smaller than 1(groove controlled) the alignment increases as the ridge size decreases, and when the ratio is larger than 1(ridge controlled), the alignment is reduced as the width of the grooves decreases. The migration rate and neurite extension of DRG neurons were greatest on 10 μm/10 μm and 30 μm/30 μm micropatterned PLGA films. Based on the data, the 10 μm/10 μm and 30 μm/30 μm micropatterned PLGA films are the optimized ridge/groove surface patterns for the construction of nerve repair devices.
文摘After decades of research,peripheral nerve injury and repair still frequently results in paralysis,chronic pain and neuropathies leading to severe disability in patients.Current clinically available nerve conduits only provide crude guidance of regenerating axons across nerve gap without additional functionality.FK506(Tacrolimus),an FDA approved immunosuppressant,has been shown to enhance peripheral nerve regeneration but carries harsh side-effects when delivered systemically.The objective of this study was to develop and evaluate a bioresorbable drug delivery system capable of local extended delivery of FK506 that also provides topological guidance cues to guide axon growth via microgrooves.Photolithography was used to create micropatterned poly(lactide-co-glycolic acid)(PLGA) films embedded with FK506.Non-patterned,10/10 μm(ridge/groove width),and 30/30 μm patterned films loaded with 0,1,and 3 μg/cm2 FK506 were manufactured and characterized.In vitro FK506 rate of release testing indicated that the films are capable of an extended(at least 56 days),controlled,and scalable release of FK506.Neurite extension bioactivity assay indicated that FK506 released from the films(concentration of samples tested ranged between 8.46–19.7 ng/m L) maintained its neural bioactivity and promoted neurite extension similar to control FK506 dosages(10 ng/m L FK506).The multi-functional FK506 embedded,micropatterned poly(lactide-co-glycolic acid) films developed in this study have potential to be used in the construction of peripheral nerve repair devices.
