Brittany L. Banik

Polymeric nanoparticles: the future of nanomedicine

Polymeric nanoparticles (NPs) are one of the most studied organic strategies for nanomedicine. Intense interest lies in the potential of polymeric NPs to revolutionize modern medicine. To determine the ideal nanosystem for more effective and distinctly targeted delivery of therapeutic applications, particle size, morphology, material choice, and processing techniques are all research areas of interest. Utilizations of polymeric NPs include drug delivery techniques such as conjugation and entrapment of drugs, prodrugs, stimuli-responsive systems, imaging modalities, and theranostics. Cancer, neurodegenerative disorders, and cardiovascular diseases are fields impacted by NP technologies that push scientific boundaries to the leading edge of transformative advances for nanomedicine.

Synthesis and characterization of biomimetic citrate‐based biodegradable composites

Natural bone apatite crystals, which mediate the development and regulate the load-bearing function of bone, have recently been associated with strongly bound citrate molecules. However, such understanding has not been translated into bone biomaterial design and osteoblast cell culture. In this work, we have developed a new class of biodegradable, mechanically strong, and biocompatible citrate-based polymer blends (CBPBs), which offer enhanced hydroxyapatite binding to produce more biomimetic composites (CBPBHAs) for orthopedic applications. CBPBHAs consist of the newly developed osteoconductive citrate-presenting biodegradable polymers, crosslinked urethane-doped polyester and poly (octanediol citrate), which can be composited with up to 65 wt % hydroxyapatite. CBPBHA networks produced materials with a compressive strength of 116.23 ± 5.37 MPa comparable to human cortical bone (100-230 MPa), and increased C2C12 osterix gene and alkaline phosphatase gene expression in vitro. The promising results above prompted an investigation on the role of citrate supplementation in culture medium for osteoblast culture, which showed that exogenous citrate supplemented into media accelerated the in vitro phenotype progression of MG-63 osteoblasts. After 6 weeks of implantation in a rabbit lateral femoral condyle defect model, CBPBHA composites elicited minimal fibrous tissue encapsulation and were well integrated with the surrounding bone tissues. The development of citrate-presenting CBPBHA biomaterials and preliminary studies revealing the effects of free exogenous citrate on osteoblast culture shows the potential of citrate biomaterials to bridge the gap in orthopedic biomaterial design and osteoblast cell culture in that the role of citrate molecules has previously been overlooked.

Multiscale Poly-(ϵ-caprolactone) Scaffold Mimicking Non-linearity in Tendon Tissue Mechanics

Regenerative medicine plays a critical role in the future of medicine. However, challenges remain to balance stem cells, biomaterial scaffolds, and biochemical factors to create successful and effective scaffold designs. This project analyzes scaffold architecture with respect to mechanical capability and preliminary mesenchymal stem cell response for tendon regeneration. An electrospun fiber scaffold with tailorable properties based on a “Chinese-fingertrap” design is presented. The unique criss-crossed fiber structures demonstrate non-linear mechanical response similar to that observed in native tendon. Mechanical testing revealed that optimizing the fiber orientation resulted in the characteristic “S”-shaped curve, demonstrating a toe region and linear elastic region. This project has promising research potential across various disciplines: vascular engineering, nerve regeneration, and ligament and tendon tissue engineering.Lay SummaryA novel scaffold created from biodegradable fibers and incorporating unique criss-cross fiber geometry was synthesized. The scaffold recapitulated the complex non-linearity in mechanics of tendon and ligament tissues. Furthermore, the scaffold supported the growth of mesenchymal stem cells, and preliminary data suggests that the scaffold geometry encourages the differentiation of mesenchymal stem cells towards tendon.

Human Mesenchymal Stem Cell Morphology and Migration on Microtextured Titanium

The implant used in spinal fusion procedures is an essential component to achieving successful arthrodesis. At the cellular level, the implant impacts healing and fusion through a series of steps: first, mesenchymal stem cells (MSCs) need to adhere and proliferate to cover the implant; second, the MSCs must differentiate into osteoblasts; third, the osteoid matrix produced by the osteoblasts needs to generate new bone tissue, thoroughly integrating the implant with the vertebrate above and below. Previous research has demonstrated that microtextured titanium is advantageous over smooth titanium and PEEK implants for both promoting osteogenic differentiation and integrating with host bone tissue; however, no investigation to date has examined the early morphology and migration of MSCs on these surfaces. This study details cell spreading and morphology changes over 24 h, rate and directionality of migration 6–18 h post-seeding, differentiation markers at 10 days, and the long-term morphology of MSCs at 7 days, on microtextured, acid-etched titanium (endoskeleton), smooth titanium, and smooth PEEK surfaces. The results demonstrate that in all metrics, the two titanium surfaces outperformed the PEEK surface. Furthermore, the rough acid-etched titanium surface presented the most favorable overall results, demonstrating the random migration needed to efficiently cover a surface in addition to morphologies consistent with osteoblasts and preosteoblasts.

Polymeric Biomaterials in Nanomedicine

Polymeric nanomaterial-based therapeutics play a key role in the field of medicine in treatment areas such as drug delivery, tissue engineering, cancer, diabetes, and neurodegenerative diseases. Advantages in the use of polymers over other materials for nanomedicine include increased functionality, design flexibility, improved processability, and, in some cases, biocompatibility. However, with the excitement surrounding the use of nanomaterials for therapeutic and diagnostic biological applications, there are also health and safety concerns. This chapter introduces nanomedicine and the use of both natural and synthetic polymeric biomaterials, focuses on specific current polymeric nanomedicine applications and research, and concludes with the challenges of nanomedicine research.

Interaction of responsive/switchable surfaces with cells

Abstract This chapter will explore the properties altered by switchable materials and subsequently the effect on cell behaviors. Topics will explore cell phenotypes from early adhesion through differentiation. Material behaviors considered will include, but are not limited to, altered surface chemistries (e.g. hydrophilic to hydrophobic); altered surface geometries (e.g. shape or stiffness change in response to a stimulus); and altered factor release (e.g. stimulus triggered release of a growth factor). Finally, the chapter will conclude by exploring the future of switchable materials and how they can exploit multiple cell phenotypes by responding to cell-generated stimuli (e.g. a proliferative cell population generates more tension as they reach confluence which promotes release of a growth factor driving differentiation).

Correction to: Mesenchymal Stem Cell Deformability and Implications for Microvascular Sequestration

This article was updated to correct the spelling of author Brittany L. Banik’s name.

Structural properties of starch-chitosan-gelatin foams and the impact of gelatin on MC3T3 mouse osteoblast cell viability

BackgroundThis study examines the effects of adding gelatin to a starch-chitosan composite foam, focusing on the altered structural and biological properties. The compressive modulus of foams containing different gelatin concentrations was tested in dry, wet, and lyophilized states. MC3T3 mouse osteoblast cells were used to test the composite’s ability to support cell growth. The stability of the foams in α-MEM culture media with and without cells was also examined.ResultsIt was found that for dry foams, the compressive modulus increased with increasing gelatin content. For foams tested in wet and lyophilized states, the compressive modulus peaked at a gelatin concentration of 2.5% and 5%, respectively. The growth of MC3T3 mouse osteoblast cells was tested on the foams with different gelatin concentrations. The addition of gelatin had a positive effect on the cell growth and proliferation.ConclusionThe composite foam containing gelatin improved cell growth and is only dissolved by the growing cells at a rate influenced by the initial concentration of gelatin added to the foam.

Bio-Instructive Scaffolds for Musculoskeletal Interfaces

Tissue interfaces are integral to the function of many tissues and for the synchronous interaction amongst tissues to create a functional whole organism. From a tissue engineering perspective, the interface presents a unique challenge compared to designing a scaffold to replace or repair bulk tissue. It is at the interface that one tissue ends and another begins and where the forces and biochemistry must be correctly transferred so that the connected tissues coordinate to function as a whole. Tissue interfaces are critical to ultimately fulfill the mechanical, physical, and biochemical responses necessary within the body. This chapter will cover the following musculoskeletal interfaces: muscle:tendon (myotendinous), motor neuron:muscle fiber (neuromuscular junctions), cartilage:bone (osteochondral), bone:tendon (osteotendinous), and bone:ligament (osteoligamentous). Key parameters for these musculoskeletal interfaces, such as relevant design rationales, the structure–function relationships, and the formation and maintenance of multitissue systems, will be reviewed and discussed.