Biology subjects

Delgado, D.

Publications and source records attributed to Delgado, D..

3 recordsLinked to original sources

bioRxiv2025

Particle-based hydrogel inks and support matrices for biofabricating structural complexity, soluble gradients, and cell-lined channels in fully granular bioprinted systems

Towards achieving biomimetic complexity in biofabricated systems, an all-granular bioprinting system might use particle-based hydrogel inks to establish structures within a particle-based support matrix. In such a system, the granular support matrix can be designed to persist in the final construct and include cells incorporated prior to printing. To biofabricate complexity, bioprinting can introduce high-resolution heterogeneous structures that guide cell behaviors. The designs of the granular ink and support hydrogels are crucial to achieving complexity. High resolution structures and channels depend on small particles that flow and can be stabilized, and that can be printed and then removed, respectively. Herein, an all-granular system is described that used a granular formulation of an established, tunable hyaluronic acid-based hydrogel as the basis for a support matrix and a small particle gelatin hydrogel as an ink. Towards facilitating stabilization of the printed structure and flow during printing, the support and ink materials included soluble, interstitial components, and all exhibited yield stress behaviors characteristic of granular hydrogel systems. The support matrixs viscoelastic properties were dependent on intraparticle hydrogel network design, and it could be stabilized against flow by photoinitiated crosslinking. The gelatin ink could form fine filaments, as small as 100 {micro}m in testing here, and melted to leave channels within crosslinked support matrices. Channels could support flows introduced by hydrostatic pressure and could be used to rapidly transport soluble factors into the construct, which could be used to establish soluble gradients by diffusion and support cell viability. The all-granular system supported printing of complex, multimaterial structures, with feature resolution on the order of 100 {micro}m and spatial positioning on the order of 10s {micro}m. The process and materials exhibited biocompatibility with respect to cells included within the support matrix during printing or introduced into channels to begin establishing endothelialized bioprinted vessels.

bioengineering↗

bioRxiv2023

Tree demographic strategies largely overlap across succession in Neotropical wet and dry forest communities

Secondary tropical forests play an increasingly important role for carbon budgets and biodiversity conservation. Understanding successional trajectories is therefore imperative for guiding forest restoration and climate change mitigation efforts. Forest succession is driven by the demographic strategies - combinations of growth, mortality and recruitment rates - of the tree species in the community. However, our understanding of demographic diversity in tropical tree species stems almost exclusively from old-growth forests. Here, we assembled demographic information from repeated forest inventories along chronosequences in two wet (Costa Rica, Panama) and two dry (Mexico) Neotropical forests to assess whether the range of demographic strategies present in a community shifts across succession. We calculated demographic rates for >500 tree species while controlling for canopy status to compare demographic diversity in early successional (0-30 years), late successional (30-120 years) and old-growth forests. We quantified demographic diversity using two-dimensional hypervolumes of pairs of demographic rates and assessed whether shifts in demographic strategies were caused by intra-specific changes in demographic rates across succession or by species turnover. We expected that demographic strategies would shift from faster life-histories (fast growth, high mortality, high recruitment) in early successional forests to slower life histories (slow growth, low mortality, low recruitment) in old-growth forests and that shifts would be stronger in wet than in dry forests due to more pronounced differences in environmental conditions between early successional and old-growth forests. We also expected that demographic diversity would increase with succession. We found that demographic strategies largely overlapped across successional stages and that early successional stages already covered the full spectrum of demographic strategies found in old-growth forests. An exception was a group of species characterized by exceptionally high mortality rates that was confined to early successional stages in the two wet forests. Demographic diversity did not increase with succession. Our results suggest that current understanding of demographic strategies of tropical tree species, which has been generated mostly from long-term forest monitoring plots in old-growth forests, is largely representative of demographic diversity in general, and that demographic diversity recovers quickly during succession.

ecology↗

bioRxiv2020

Functional modeling of NMIHBA-causing PRUNE1 variants reveals a requirement for its exopolyphosphatase activity.

Neurodevelopmental disorder with microcephaly, hypotonia, and variable brain anomalies (NMIHBA) is an autosomal recessive neurodevelopmental and neurodegenerative disorder characterized by global developmental delay and severe intellectual disability. Microcephaly, progressive cortical atrophy, cerebellar hypoplasia and delayed myelination are neurological hallmarks in affected individuals. NMIHBA is caused by biallelic variants in PRUNE1 encoding prune exopolyphosphatase 1. We provide in-depth clinical description of two affected siblings harboring compound heterozygous variant alleles, c.383G>A (p.Arg128Gln), c.520G>T (p.Gly174*) in PRUNE1. To gain insights into disease biology, we biochemically characterized missense variants within the conserved N-terminal aspartic acid-histidine-histidine (DHH) motif and provide evidence that they result in the destabilization of protein structure and/or loss of exopolyphosphatase activity. Genetic ablation of Prune1 results in midgestational lethality in mice, associated with perturbations to embryonic growth and vascular development. Our findings suggest that NMIHBA results from hypomorphic variant alleles in humans and underscore the potential key role of PRUNE1 exopolyphoshatase activity in neurodevelopment.

genetics↗