Several members of the Benoit Lab presented their research at the 10th World Biomaterials Congress (WBC) this weekend, held in Montreal. The largest gathering of Biomaterial Research, the WBC includes over 1,200 oral presentations and 2,400 poster presentations. Their respective presentation topics are below.
Enzymatically-responsive poly(ethylene glycol) hydrogels for the controlled delivery of
Introduction: Therapeutic angiogenesis holds great potential within regenerative medicine approaches, where insufficient vascularization limits construct size, complexity, and anastomosis with host vasculature. Many pro-angiogenic approaches have been developed, often via delivery of angiogenic proteins or peptides. Peptides typically mimic the bioactivity of larger proteins or growth factors, and offer advantages over traditional protein delivery. However, like proteins, peptides suffer from rapid clearance and poor pharmacokinetics when delivered systemically. Therefore, a poly(ethylene glycol) (PEG) hydrogel-based platform technology was developed to control and sustain peptide drug release via matrix metalloproteinase (MMP) activity.
Localized and Sustained Delivery of small interference RNA (siRNA) from Poly(Ethylene Glycol) (PEG) Hydrogels to Enhance Fracture Healing
Introduction: Impaired fracture healing, which commonly stems from reduced mesenchymal stem cell (MSC) osteogenic capacity, is a major clinical challenge-. To augment MSC function and subsequent fracture healing, known inhibitors of bone formation can be downregulated. For example, mouse knockouts of WW domain containing E3 ubiquitin protein ligase 1 (WWP1) exhibit robust fracture healing. To realize clinically-relevant approaches to enhance fracture healing motivated by gene knockout studies, siRNA delivery can be exploited. However, siRNA delivery has many challenges including inefficient delivery vehicles that are incapable of local and sustained delivery of protected siRNA to achieve tissue regeneration. Thus, we developed and tested a hybrid nanoparticle (NP)/hydrogel delivery system where NPs protect siRNA and increase siRNA delivery efficiency, while PEG hydrogels provide localized and sustained siRNA delivery by controlling release of embedded siRNA/NPs.
Nanoparticle-mediated delivery of siRNAs modulates mesenchymal stem cell differentiation
Introduction: Mesenchymal stem cells (MSC) are an attractive cell source for tissue engineering approaches due to multilineage differentiation. However, controlling MSC fate is critical for tissue regeneration. microRNAs (miRNA) are known as ‘master regulators’ of differentiation, serving to integrate the myriad of complex signals driving differentiation . However, the use of small interfering RNA (siRNA), which are exogenous analogs of miRNA, to control MSC fate has been largely unexplored due to a paucity of delivery systems and poor appreciation for siRNAs necessary to achieve differentiation. Towards this end, we analyzed temporal expression of multiple miRNAs in MSCs undergoing osteogenesis in vitro. Subsequently, we used polymeric nanoparticles (NPs) previously shown to achieve successful siRNA delivery to MSCs  to deliver siRNA mimicking the identified miRNA while monitoring MSC differentiation.
Strategies to maintain acinar cell phenotype in vitro utilizing poly(ethylene glycol) hydrogels
Introduction: Over 500,000 people are diagnosed with head and neck cancers per year worldwide. Radiation therapy for these cancers causes extensive and permanent damage to secretory acinar cells within the salivary glands leading to permanent dry mouth for which no curative therapy exists. Cell-based therapies developed by the suspension culture of primary submandibular gland (SMG) cells has shown efficacy in restoring function after gland irradiation. However, regeneration is variable and the mechanism resulting in partial acinar regeneration in vivo is unclear,. To control acinar cell survival and function for subsequent transplantation in vivo, we are developing biomimetic poly(ethylene glycol) (PEG) hydrogels to culture primary SMG cells.
Peptide-functionalized polymers localize to remodeling osteoporotic bone
Introduction: Increased bone resorption by osteoclasts relative to bone formation by osteoblasts culminates in osteoporosis, a disease of low bone mass. There are myriad drugs in preclinical analyses that may enhance bone regeneration. However, these are largely small molecule drugs, which suffer from less than 1% bone accumulation. While bone targeting strategies exist, these approaches are general for bone matrix and not specific to where cellular remodeling is occurring, limiting targeted drug pharmacodynamics. We previously identified a peptide, TPLSYLKGLVTV, with high affinity to tartrate-resistant acid phosphatase (TRAP), a protein secreted by osteoclasts during the resorptive phase of bone remodeling. Targeting osteoanabolics to TRAP may enhance drug pharmacodynamics by increasing osteoblast activity specifically at sites of bone remodeling. This work developed TRAP-targeted polymer carriers as a platform for subsequent drug delivery approaches.