Finely Tuned Temporal and Spatial Delivery of GDNF Promotes Enhanced Nerve Regeneration in a Long Nerve Defect Model

MarquardtLaura, M; EeXueping,; Iyer, Nisha; HunterDaniel,; MackinnonSusan, E; Wood, Matthew D.; Sakiyama-ElbertShelly, E

doi:10.1089/ten.tea.2015.0311

Cited by 62 publications

(56 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…[71][72][73][74][75][76][77][78] These boosted grafts, may prove effective in some instances of neural regeneration, including sustainment of host neurons during long distance gap repairs. 79,80 However, despite these novel engineering feats, even with the addition of biological fillers, acellular grafts remain unable to address overall shortcomings in nerve regeneration. 81 Often, undesirable results have been reported using "smart materials", such as "the candy store effect".…”

Section: Discussionmentioning

confidence: 99%

Tissue Engineered Axon-Based “Living Scaffolds” Promote Survival of Spinal Cord Motor Neurons Following Peripheral Nerve Repair

Maggiore

Burrell

Browne

et al. 2019

Preprint

View full text Add to dashboard Cite

Peripheral nerve injury (PNI) impacts millions annually, often leaving debilitated patients with minimal repair options to improve functional recovery. Our group has previously developed tissue engineered nerve grafts (TENGs) featuring long, aligned axonal tracts from dorsal root ganglia (DRG) neurons that are fabricated in custom bioreactors using the process of axon "stretch-growth". We have shown that TENGs effectively serve as "living scaffolds" to promote regeneration across segmental nerve defects by exploiting the newfound mechanism of axonfacilitated axon regeneration, or "AFAR", by simultaneously providing haptic and neurotrophic support. To extend this work, the current study investigated the efficacy of living versus non-living regenerative scaffolds in preserving host sensory and motor neuron cell health, using retrograde dye transport as a proxy, following bridging of segmental nerve defects. Rats were assigned across five groups: naïve or repair using autograft, nerve guidance tube (NGT) with collagen, NGT + non-aligned DRG populations in collagen, or TENGs. We found that TENG repairs yielded equivalent regenerative capacity as autograft repairs based on preserved health of host spinal cord motor neurons and acute axonal regeneration, whereas NGT repairs or DRG neurons within an NGT exhibited reduced motor neuron preservation and diminished regenerative capacity.These acute regenerative benefits ultimately resulted in enhanced levels of functional recovery in animals receiving TENGs, at levels matching those attained by autografts. Our findings indicate that when used to bridge segmental nerve defects, TENGs preserve host spinal cord motor neuron health and regenerative capacity without sacrificing an otherwise uninjured nerve (as in the case of the autograft), and therefore represent a promising alternative strategy for neurosurgical repair following PNI.2 HIGHLIGHTS

show abstract

Section: Discussionmentioning

confidence: 99%

Tissue Engineered Axon-Based “Living Scaffolds” Promote Survival of Spinal Cord Motor Neurons Following Peripheral Nerve Repair

Maggiore

Burrell

Browne

et al. 2019

Preprint

View full text Add to dashboard Cite

show abstract

“…) and neurogenesis (Marquardt et al . ). GFs, in particular, orchestrate and modulate pulpal regeneration with several members of the transforming GF superfamily (Cassidy et al .…”

Section: Reviewmentioning

confidence: 97%

“…Indeed, a problem with pulpal biomarkers and MMPs in particular is that they are not just destructive in nature; they also increase the bioactivity and reparative capacity of DMCs by further digesting the extracts (Okamoto et al 2018). DMCs contain multiple bioactive components, including GFs, chemokines, cytokines, MMPs and bioactive proteins , which modulate a range of processes critical to repair, including chemotaxis (Smith et al 2012, Galler et al 2016a, angiogenesis (Roberts-Clark & Smith 2000), mineralization (Tomson et al 2013), stem cell (SC) recruitment (Fayazi et al 2017) and neurogenesis (Marquardt et al 2015). GFs, in particular, orchestrate and modulate pulpal regeneration with several members of the transforming GF superfamily (Cassidy et al 1997, Galler et al 2015 and insulin-like GFs (Finkelman et al 1990) present in DMC extracts.…”

Section: Role Of Dentine In Repairmentioning

confidence: 99%

Management of deep caries and the exposed pulp

et al. 2019

View full text Add to dashboard Cite

Caries prevalence remains high throughout the world, with the burden of disease increasingly affecting older and socially disadvantaged groups in Western cultures. If left untreated, caries will advance through dentine stimulating pulpitis and eventually pulp infection and necrosis; however, if conservatively managed, pulpal recovery occurs even in deep carious lesions. Traditionally, deep caries management was destructive with nonselective (complete) removal of all carious dentine; however, the promotion of minimally invasive biologically based treatment strategies has been advocated for selective (partial) caries removal and a reduced risk of pulp exposure. Selective caries removal strategies can be one‐visit as indirect pulp treatment or two‐visit using a stepwise approach. Management strategies for the treatment of the cariously exposed pulp are also shifting with avoidance of pulpectomy and the re‐emergence of vital pulp treatment (VPT) techniques such as partial and complete pulpotomy. These changes stem from an improved understanding of the pulp–dentine complex's defensive and reparative response to irritation, with harnessing the release of bioactive dentine matrix components and careful handling of the damaged tissue considered critical. Notably, the development of new pulp capping materials such as mineral trioxide aggregate, which although not an ideal material, has resulted in more predictable treatments from both a histological and a clinical perspective. Unfortunately, the changes in management are only supported by relatively weak evidence with case series, cohort studies and preliminary studies containing low patient numbers forming the bulk of the evidence. As a result, critical questions related to the superiority of one caries removal technique over another, the best pulp capping biomaterial or whether pulp exposure is a negative prognostic factor remain unanswered. There is an urgent need to promote minimally invasive treatment strategies in Operative Dentistry and Endodontology; however, the development of accurate diagnostic tools, evidence‐based management strategies and education in management of the exposed pulp are critical in the future.

show abstract

“…One goal of our hybrid ANA approach was to increase growth factor availability by incorporating cells within an ANA. Incorporating cells via nerve within a long ANA (hybrid ANA) increased neurotrophic factor expression in regions of the hybrid ANAs, where increased growth factor availability is known to improve nerve regeneration for acellular scaffolds . Indeed, Gdnf and Bdnf expression were highly elevated in the middle and distal graft in the hybrid ANA compared with the control ANA corresponding to increased axon regeneration.…”

Section: Discussionmentioning

confidence: 99%

Nerve stepping stone has minimal impact in aiding regeneration across long acellular nerve allografts

et al. 2017

Self Cite

View full text Add to dashboard Cite

show abstract

Finely Tuned Temporal and Spatial Delivery of GDNF Promotes Enhanced Nerve Regeneration in a Long Nerve Defect Model

Cited by 62 publications

References 48 publications

Tissue Engineered Axon-Based “Living Scaffolds” Promote Survival of Spinal Cord Motor Neurons Following Peripheral Nerve Repair

Tissue Engineered Axon-Based “Living Scaffolds” Promote Survival of Spinal Cord Motor Neurons Following Peripheral Nerve Repair

Management of deep caries and the exposed pulp

Nerve stepping stone has minimal impact in aiding regeneration across long acellular nerve allografts

Contact Info

Product

Resources

About