Biology subjects

Hollister, S. J.

Publications and source records attributed to Hollister, S. J..

3 recordsLinked to original sources

bioRxiv2023

Design and characterization of porous poly(glycerol-dodecanedioate) scaffolds for cartilage repair

Synthetic polymeric scaffolds play an important role in establishing the microenvironment for chondrocytes in engineered cartilage. A three-dimensional pore network allows cell accommodation and supports extracellular matrix (ECM) production by chondrocytes. Ligand coating and biomechanical properties of scaffolds guide regeneration of functional cartilage by mediating cell attachment and establishing the local strain environment. Poly(glycerol-dodecanedioate) (PGD) is a novel biodegradable elastomer with nonlinear-elastic properties similar to native cartilage. However, its harsh curing environments limit the feasibility of common strategies for pore creation in polymeric scaffolds. Herein, we developed porous PGD (pPGD) scaffolds with tailorable pore structures using an inverse molding method and evaluated the range of scaffold structural parameters achievable and their subsequent mechanical properties. The influence of coating PGD with various ECM ligands on the cell shape, metabolic activity, and ECM production of human articular chondrocytes (hACs) was evaluated. pPGD scaffolds were created with pore sizes ranging from 250 - 1000 m, resulting in 20 - 50% porosity. The morphology and metabolic activity of hACs on PGD were regulated by the type of ligand coating used. When compared to tissue culture plastic, PGD enhanced ECM production in monolayer cultures. Finite element analysis showed that the tensile strains that developed on the pores surfaces were at levels shown to be anabolic for hACs. The predicted strain profile varied with pore size and porosity under load, demonstrating that the pore structural parameters could be tuned to optimize cellular-level strains. These results suggest that pPGD scaffolds have the potential to guide cartilage regeneration. Statement of SignificancePrevious studies have established the importance of designing pore geometry and surface properties in engineered cartilage tissue constructs. This work reports the development and assessment of pPGD scaffolds with tunable pore and surface parameters for cartilage regeneration. The cellular-level strain that cells may experience inside the pores was influenced by the scaffolds pore geometry. Ligand coating on PGD balanced out the less ideal properties of the material itself and regulated the shape, attachment, metabolic activity, and ECM production of hACs during in vitro culture. These findings highlight how intelligent design of scaffold parameters can optimize chondrocyte function during 3D culture by tuning ligand presentation and cellular-level strain profiles.

bioengineering↗

bioRxiv2021

Repair of critical-size porcine craniofacial bone defects using a collagen-polycaprolactone composite biomaterial

Regenerative medicine approaches for massive craniomaxillofacial bone defects face challenges associated with the scale of missing bone, the need for rapid graft-defect integration, and challenges related to inflammation and infection. Mineralized collagen scaffolds have been shown to promote mesenchymal stem cell osteogenesis due to their porous nature and material properties, but are mechanically weak, limiting surgical practicality. Previously, these scaffolds were combined with 3D-printed polycaprolactone mesh to form a scaffold-mesh composite to increase strength and promote bone formation in sub-critical sized porcine ramus defects. Here, we compare the performance of mineralized collagen-polycaprolactone composites to the polycaprolactone mesh in a critical-sized porcine ramus defect model. While there were no differences in overall healing response between groups, our data demonstrated broadly variable metrics of healing regarding new bone infiltration and fibrous tissue formation. Abscesses were present surrounding some implants and polycaprolactone polymer was still present after 9-10 months of implantation. Overall, while there was limited successful healing, with 2 of 22 implants showed substantial levels of bone regeneration, and others demonstrating some form of new bone formation, the results suggest targeted improvements to improve repair of large animal models to more accurately represent craniomaxillofacial bone healing. Notably, strategies to increase osteogenesis throughout the implant, modulate the immune system to support repair, and employ shape-fitting tactics to avoid implant micromotion and resultant fibrosis. Improvements to the mineralized collagen scaffolds involve changes in pore size and shape to increase cell migration and osteogenesis and inclusion or delivery of factors to aid vascular ingrowth and bone regeneration.

bioengineering↗

bioRxiv2019

Real-time monitoring of mechanical cues in the regenerative niche reveal dynamic strain magnitudes that enhance bone repair

Mechanical loads exerted on the skeleton during activities such as walking are important regulators of bone repair, but dynamic biomechanical signals are difficult to measure inside the body. The inability to measure the mechanical environment in injured tissues is a significant barrier to developing integrative regenerative and rehabilitative strategies that can accelerate recovery from fracture, segmental bone loss, and spinal fusion. Here we engineered an implantable strain sensor platform and measured strain across a bone defect in real-time throughout rehabilitation. We used the sensor to longitudinally quantify mechanical cues imparted by a load-sharing fixation plate that significantly enhanced bone regeneration in rats. We found that sensor readings correlated with the status of healing, suggesting a potential role for strain sensing as an X-ray-free healing assessment platform. This study demonstrates a promising approach to quantitatively develop and exploit mechanical rehabilitation strategies that enhance bone repair.

bioengineering↗