Juana Mendenhall

ConspectusAt Morehouse College, one of the nation's top liberal arts historically black colleges and universities (HBCU) for African American men, research experiences are used to enhance the liberal arts educational experience. Securing research funding to train HBCU students is highly competitive and challenging due to the review process that is typically vetted by scientists from research-intensive universities who may not be familiar with the HBCU enterprise that may be comprised of insolvent infrastructures. In this Account, the synthesis and preparation of synthetic polymeric biomaterials that are used to facilitate or support changes in biological processes, enhance mechanical properties, and foster tissue growth in three dimensions (3D) under disease conditions will be discussed. The use of biomaterials to help control biological processes in disease states is limited. Hence, the fabrication of 3D scaffolds with chemical variability to grow or repair damaged tissues by inhibiting molecular pathways shows promise by controlling the cellular response to recapitulate 3D tissues and organs. The Mendenhall laboratory at Morehouse College uses 3D biomaterials to solve biological problems by probing cellular mechanistic pathways using natural products and nanoparticles. Toward this end, we have fabricated and manufactured 3D biomaterial scaffolds using chemical strategies to mitigate biological processes to help restore pristine tissue properties. Hydrogels are 3D polymeric matrixes that swell in aqueous environments and support cell growth that later infuriates the 3D matrix to create new tissue(s). In contrast, electrospun fibers use high electric fields to create porous 3D polymeric structures that can be used to create 3D tissue molds.The synergistic use of 3D biomaterial templates that can inhibit cellular damage while providing a mechanically strong scaffold to support regenerative tissue growth is essential to creating the next generation of biomaterials. This approach will require foresight using tools from synthetic biology, molecular biology, autonomous processes, advanced biomanufacturing, and machine learning (ML). The use of several biomaterials has been explored by the Mendenhall laboratory to design, prepare, fabricate, characterize, and evaluate 3D electrospun fibers and hydrogels containing hybrid compositions of polylactic acid (PLA), poly(n-vinylcaprolactam) (PVCL), cellulose acetate (CA), and methacrylated hyaluronic acid (meHA). This work contributed to the newly fabricated PVCL-CA fibers with morphological changes and nanoscale fiber hydrophobic surface properties. While the use of electrospun fibers can create hierarchal scaffolds for bone tissue engineering, the use of injectable gels for nonporous tissues such as articular cartilage presents another compelling biomaterial challenge. Using graft polymerization, we prepared PVLC-graft-HA and studied the effect of lower critical solution temperatures (LCSTs), gelation temperatures, and mechanical properties using temperature-controlled rheology. Additionally, we reported that articular cartilage (chondrocyte) cells seeded in PVCL-g-HA gels and incubated at hypoxia 1% O₂ produced a 10-fold increase in extracellular matrix proteins (collagen) after 10 days. This work supported exploring new approaches to protecting chondrocyte cells under hypoxia using a 3D scaffold technology.

Osteoarthritis (OA) is a degenerative disease characterized by articular cartilage (AC) degradation that affects more than 30 million people in the USA. OA is managed with symptom-alleviating medications. Matrix-assisted autologous chondrocyte transplantation (MACT) is a tissue-engineered option, but current products are expensive and lack mechanical tunability or processability to match defect mechanical properties and anatomical shapes. Here, we explore the efficacy of a biocompatible hydrogel-based scaffold composed of sodium alginate, gelatin, and gum Arabic—referred to by SA–GEL–GA—to support bovine articular chondrocyte (bAChs) proliferation, pericellular matrix (PCM), and extracellular matrix (ECM) production. bAChs were grown for 45 days in SA–GEL–GA. Their viability, their live/dead status, histological staining, biochemical assays for glycosaminoglycans (GAGs) and collagen, atomic force microscopy (AFM) imaging, and immunofluorescence staining of collagen I, collagen II, aggrecan, and CD44 were assessed. We found that SA–GEL–GA was not cytotoxic, induced cellular proliferation by 6.1-fold while maintaining a round morphology, and supported ECM deposition by producing 3.9-fold more GAG compared to day 0. bAChs transformed into chondrons and produced a PCM enriched with collagen II (3.4-fold), aggrecan (1.7-fold), and CD44 (1.3-fold) compared to day 0. In summary, SA–GEL–GA supported the proliferation, ECM production, and PCM production of bAChs in vitro.

Cartilage repair presents a daunting challenge in tissue engineering applications due to the low oxygen conditions (hypoxia) affiliated in diseased states. Hence, the use of biomaterial scaffolds with unique variability is imperative to treat diseased or damaged cartilage. Thermosensitive hydrogels show promise as injectable materials that can be used as tissue scaffolds for cartilage tissue regeneration. However, uses in clinical applications are limited to due mechanical stability and therapeutic efficacy to treat diseased tissue. In this study, several composite hydrogels containing poly(N-vinylcaprolactam) (PVCL) and methacrylated hyaluronic acid (meHA) were prepared using free radical polymerization to produce PVCL-graft-HA (PVCL-g-HA) and characterized using Fourier transform infrared spectroscopy, nuclear magnetic resonance, and scanning electron microscopy. Lower critical solution temperatures and gelation temperatures were confirmed in the range of 33–34°C and 41–45°C, respectively. Using dynamic sheer rheology, the temperature dependence of elastic (G′) and viscous (G″) modulus between 25°C and 45°C, revealed that PVCL-g-HA hydrogels at 5% (w/v) concentration exhibited the moduli of 7 Pa (G′) to 4 Pa (G″). After 10 days at 1% oxygen, collagen production on PVCL-g-HA hydrogels was 153 ± 25 μg/mg (20%) and 106 ± 18 μg/mg showing a 10-fold increase compared to meHA controls. These studies show promise in PVCL-g-HA hydrogels for the treatment of diseased or damaged articular cartilage. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1863–1873, 2017.

Poly(2-methoxystyrene)s (P2MS) were synthesized using n-BuLi in THF and toluene at various temperatures. At −20°C and higher temperatures, toluene was an effective polymerization solvent for synthesizing poly(2-methoxystyrene). Under these conditions, polymers with good yields and reasonable molecular weight distributions were obtained. Polymers synthesized under all conditions were isotactic; the most highly isotactic polymer was obtained in toluene at −20°C. The m (isotactic dyad) content of the polymers synthesized in toluene at 0°C and −20°C was 0.65 and 0.74, respectively. Optically active helical (+) and (−) P2MS were synthesized by asymmetric polymerization utilizing (+) or (−) [2,3-dimethoxy1,4(dimethylamino)butane] (DDB)/tolyl lithium initiating complex in toluene. Asymmetric polymerizations were also carried out at 0°C to synthesize optically active polymers. The optical rotations of the polymers were found to be dynamic and reversible, strongly suggesting contribution of the chiral higher order...