With the emphasis on collagen and hydroxyapatite, the main structural components of bone tissue, synthetic grafts fall short of matching the clinical efficacy of autologous bone grafts. Excluded non-collagenous protein (NCPs) and carbohydrates also participate in critical cell signaling cascades and guide mineral deposition during intermediate stages of bone healing. By mimicking the native fracture repair process, polymeric scaffolds that incorporate calcium-binding moieties present in fibrocartilage can potentially enhance their bioactivity, mineralization, and bone growth. Likewise, coating polymeric fibers with serum albumin is an additional strategy that can impart collagen-like biofunctionality and further increase mineral deposition on the fibrous surface. Here, a combination of electrospun polycaprolactone (PCL) fibers with chondrocyte-derived decellularized extracellular matrix (dECM) and albumin coating were investigated as a fibrocartilagemimetic scaffold that can serve as a woven bone precursor for bone regeneration. PCL fibrous constructs coated with dECM and albumin are shown to synergistically increase calcium concentration and calcium phosphate (CaP) deposition in a simulated body fluid biomineralization assay. Albumin/dECM coating increased osteoblast proliferation and mineral deposition in culture. In contrast, CaP coating transformed osteoblast bone lining morphology into cuboidal phenotype and arrested their proliferation. Cell sheets of osteoblasts cultured on dECM/albumin/CaP-coated constructs exhibited an increase in calcium deposition and secretion of collagen, osteopontin, osteocalcin, and bone morphogenetic protein. These results highlight the potential of biomolecular coatings to enhance bone-mimetic properties of synthetic nanofibrous scaffolds, stimulate critical protein and mineral deposition, and augment the bone's capacity to heal. Thus, mimicking the intermediate stages of bone regeneration by incorporating calcium-binding moieties may prove to be a useful strategy for improving the clinical outcomes of synthetic bone grafts.
Precision nanomedicine can be employed as an alternative to chemo-or radiotherapy to overcome challenges associated with the often narrow therapeutic window of traditional treatment approaches, while safely inducing effective, targeted antitumor responses. Herein, we report the formulation of a therapeutic nanocomposite comprising a hyaluronic acid (HA)coated gold nanoframework (AuNF) delivery system and encapsulated IT848, a small molecule with potent antilymphoma and -myeloma properties that targets the transcriptional activity of nuclear factor kappa B (NF-κB). The porous AuNFs fabricated via a liposome-templated approach were loaded with IT848 and surfacefunctionalized with HA to formulate the nanotherapeutics that were able to efficiently deliver the payload with high specificity to myeloma and lymphoma cell lines in vitro. In vivo studies characterized biodistribution, pharmacokinetics, and safety of HA-AuNFs, and we demonstrated superior efficacy of HA-AuNF-formulated IT848 vs free IT848 in lymphoma mouse models. Both in vitro and in vivo results affirm that the AuNF system can be adopted for targeted cancer therapy, improving the drug safety profile, and enhancing its efficacy with minimal dosing. HA-AuNF-formulated IT848 therefore has strong potential for clinical translation.
Porous scaffolds play a crucial role in bone tissue regeneration and have been extensively investigated in this field. By incorporating a decellularized extracellular matrix (dECM) onto tissue-engineered scaffolds, bone regeneration can be enhanced by replicating the molecular complexity of native bone tissue. However, the exploration of porous scaffolds with anisotropic channels and the effects of dECM on these scaffolds for bone cells and mineral deposition remains limited. To address this gap, we developed a porous polycaprolactone (PCL) scaffold with anisotropic channels and functionalized it with dECM to capture the critical physicochemical properties of native bone tissue, promoting osteoblast cells’ proliferation, differentiation, biomineralization, and osteogenesis. Our results demonstrated the successful fabrication of porous dECM/PCL scaffolds with multiple channel sizes for bone regeneration. The incorporation of 100 μm grid-based channels facilitated improved nutrient and oxygen infiltration, while the porous structure created using 30 mg/mL of sodium chloride significantly enhanced the cells’ attachment and proliferation. Notably, the mechanical properties of the scaffolds closely resembled those of human bone tissue. Furthermore, compared with pure PCL scaffolds, the presence of dECM on the scaffolds substantially enhanced the proliferation and differentiation of bone marrow stem cells. Moreover, dECM significantly increased mineral deposition on the scaffold. Overall, the dECM/PCL scaffold holds significant potential as an alternative bone graft substitute for repairing bone injuries.
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