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Biology subjects

Bandara, G. C.

Publications and source records attributed to Bandara, G. C..

4 recordsLinked to original sources

Aligned basement membrane-modified collagen scaffolds for skeletal muscle tissue engineering

Biomaterial scaffolds for repairing traumatic muscle injuries require restoration of both the anisotropic architecture and basement membrane extracellular matrix cues critical to normal muscle function. To address this need, we establish a collagen-glycosaminoglycan (CG) scaffold platform pairing an aligned pore microstructure, produced via directional freeze-drying, with basement membrane protein functionalization via carbodiimide crosslinking. Laminin and/or collagen IV are successfully tethered and retained within CG scaffolds over 7 days without significantly altering pore size or alignment, confirming stable protein functionalization and preservation of scaffold architecture. Human muscle progenitor cells show excellent viability and metabolic activity in all scaffold groups, with collagen IV functionalization significantly enhancing myotube number and fusion index. Toward establishing scaffold compatibility with non-myogenic support cells, we show that neural stem cells remain viable and metabolically active across all scaffold conditions. Overall, these findings highlight the combination of aligned scaffold architecture and collagen IV functionalization as potentially impactful for skeletal muscle tissue engineering.

bioengineering↗

Aligned multicompartment collagen scaffolds support stratified myoblast and fibroblast behavior for musculotendinous tissue engineering

Injuries to musculoskeletal tissue junctions are exceedingly common and notoriously difficult to repair due to the inability to restore overlapping gradations of structural, biochemical, and mechanical signals critical to tissue interfacial integrity. This work introduces a multicompartment scaffold for muscle-tendon junction (MTJ) tissue engineering, containing distinct muscle and tendon compartments joined at a continuous interface, recapitulating the structural anisotropy, graded collagen content, and electrical excitability of the native MTJ. Collagen suspensions with or without electrically conductive poly(3,4-ethylenedioxythiophene) (PEDOT) particles representing muscle and tendon compartments respectively were carefully layered and directionally freeze-dried to form an integrated multicompartment scaffold with aligned pores mimicking the MTJ. Scanning electron microscopy (SEM) and energy-dispersive X-ray spectroscopy (EDS) confirmed the formation of a structurally anisotropic scaffold with stratified conductive polymer content, and importantly, a smooth continuous interfacial region joining the two compartments of similar scale to native MTJ. In contrast to multicompartment materials with abrupt interfaces, mechanical testing confirmed no decrease in multicompartment scaffold tensile properties relative to single compartment controls. Myoblasts and fibroblasts were successfully seeded on multicompartment scaffolds in a stratified manner while uniformly conforming to aligned scaffold contact guidance cues and maintaining metabolic activity over a week in culture. Myoblasts underwent compartment-specific differentiation while fibroblasts remained viable, even under myogenic differentiation conditions. Together, this work presents a scaffold platform integrating key structural, biochemical, and mechanical features necessary for MTJ tissue engineering.

bioengineering↗

Heparin-modified aligned collagen scaffolds enhance in vitro myogenesis

Biomaterial-based skeletal muscle tissue engineering approaches have largely focused on mimicking the 3D aligned architecture of native muscle, which is critical for guiding myotube formation and force transmission. In contrast, fewer studies incorporate glycosaminoglycan (GAG)-mediated biochemical cues despite their known role in regulating myogenesis and growth factor sequestration. In this study, we develop aligned collagen-GAG (CG) scaffolds using directional freeze-drying and systematically vary GAG content by incorporating GAGs of increasing sulfation levels (hyaluronic acid, chondroitin sulfate, and heparin). While all scaffold variants support myoblast adhesion, metabolic activity, and myotube alignment, heparin-modified collagen scaffolds significantly enhance myoblast metabolic activity and myogenic differentiation as measured by myosin heavy chain (MHC) expression and myotube size. We additionally show that heparin-modified scaffolds sequester and retain significantly higher levels of insulin-like growth factor-1 (IGF-1), a potent promoter of myogenesis, compared to other scaffold groups. Together, these results highlight the importance of optimizing GAG content in CG scaffolds for targeted applications and underscore the promise of heparin-modified CG scaffolds as a material platform for skeletal muscle tissue engineering.

bioengineering↗

Freeze-dried porous collagen scaffolds for the repair of volumetric muscle loss injuries

Volumetric muscle loss (VML) injuries are characterized by the traumatic loss of skeletal muscle resulting in permanent damage to both tissue architecture and electrical excitability. To address this challenge, we previously developed a 3D aligned collagen-glycosaminoglycan (CG) scaffold platform that supported in vitro myotube alignment and maturation. In this work, we assessed the ability of CG scaffolds to facilitate functional muscle recovery in a rat tibialis anterior (TA) model of VML. Functional muscle recovery was assessed following implantation of either non-conductive CG or electrically conductive CG-polypyrrole (PPy) scaffolds at 4, 8, and 12 weeks post-injury by in vivo electrical stimulation of the peroneal nerve. After 12 weeks, scaffold-treated muscles produced maximum isometric torque that was significantly greater than non-treated tissues. Histological analysis further supported these reparative outcomes with evidence of regenerating muscle fibers at the material-tissue interface in scaffold-treated tissues that was not observed in non-repaired muscles. Scaffold-treated muscles possessed higher numbers of M1 and M2 macrophages at the injury while conductive CG-PPy scaffold-treated muscles showed significantly higher levels of neovascularization as indicated by the presence of pericytes and endothelial cells, suggesting a persistent wound repair response not observed in non-treated tissues. Finally, only tissues treated with non-conductive CG scaffolds displayed neurofilament staining similar to native muscle, further corroborating isometric contraction data. Together, these findings show that CG scaffolds can facilitate improved skeletal muscle function and endogenous cellular repair, highlighting their potential use as therapeutics for VML injuries.

bioengineering↗