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The use of nanomaterials as carriers for the delivery of growth factors has been applied to a multitude of applications in tissue engineering. However, issues of toxicity, stability, and systemic effects of these platforms have yet to be fully understood, especially for cardiovascular applications. Here, we proposed a delivery system composed of poly(dl-lactide- co-glycolide) acid (PLGA) and porous silica nanoparticles (pSi) to deliver vascular endothelial growth factor (VEGF) and platelet-derived growth factor (PDGF). The tight spatiotemporal release of these two proteins has been proven to promote neovascularization. In order to minimize tissue toxicity, localize the release, and maintain a stable platform, we conjugated two formulations of PLGA-pSi to electrospun (ES) gelatin to create a combined ES patch releasing both PDGF and VEGF. When compared to freely dispersed particles, the ES patch cultured in vitro with neonatal cardiac cells had significantly less particle internalization (2.0 ± 1.3%) compared to free PLGA-pSi (21.5 ± 6.1) or pSi (28.7 ± 2.5) groups. Internalization was positively correlated to late-stage apoptosis with PLGA-pSi and pSi groups having increased apoptosis compared to the untreated group. When implanted subcutaneously, the ES patch was shown to have greater neovascularization than controls evidenced by increased expression of α-SMA and CD31 after 21 days. Quantitative reverse transcription-polymerase chain reaction results support increased angiogenesis by the upregulation of VEGFA, VEGFR2, vWF, and COL3A1, exhibiting a synergistic effect with the release of VEGF-A164 and PDGF-BB after 21 days in vivo. The results of this study proved that the ES patch reduced cellular toxicity and may be tailored to have a dual release of growth factors promoting localized neovascularization.

Here we reported a novel electrochemical encapsulation method to encapsulate various nanomaterials and bimolecules into collagen. The electrochemical encapsulation process involves assembling of collagen along with Nano/bio materials using an isoelectric focusing mechanism. We have showed that a wide range of Nanomaterials such as carbon nanotubes, polymeric nanoparticles, magnetic calcium phosphate nanoparticles and biomolecules can be encapsulated into collagen. These novel collagen-based composite materials possess improved electric, mechanical, antimicrobial, magnetic, bioactive properties. Thus, this novel electrochemical encapsulation process offers a means to fabricate novel biomaterials for various biomedical applications such as tendon/ligament, nerve, skin tissue engineering, tendon/ligament to bone grafts, and sutures, etc.

Structural cardiac defects, such as Tetralogy of Fallot, often requires surgical placement of a patch to expand the right ventricular outflow tract (RVOT) in an area normally consisting of contractile myocardial tissue. Current cardiac patch materials are biologically inert and will not grow with a pediatric patient, often requiring reoperations. In this study, novel multi-layered scaffolds with a polycaprolactone core, a chitosan-based scaffold, and either gelatin or decellularized porcine heart matrix were implanted into a full thickness rat right ventricle defect for up to 8 weeks. The results show that engineered scaffolds were biodegradable and promoted tissue remodeling. Histological analysis of control fixed pericardium patches showed little to no cellular infiltration, while engineered scaffolds had significant muscular and vascular cell remodeling. Quantitative MRI revealed that left ventricular ejection fractions were stabilized in all patched hearts after 8 weeks, and the right ventricular ejection fraction in hearts with engineered patches was significantly greater than hearts with control pericardium patches. In addition, patches with heart matrix promoted a denser vascular network and a higher M2/M1 inflammatory macrophage ratio when compared to patches containing only gelatin. Collectively, these results show that these multi-layered patches are capable of full thickness defect repair and regeneration.

In order to enhance the healing potential of an injured tendon, we have prepared a novel biomimetic aligned collagen-nanoparticle (NP) composite fiber using an electrochemical process. The aligned collagen-NP composite fiber is designed to affect the cellular activity of adipose-derived stem cells (ADSCs) through two different ways: (i) topographic cues from the alignment of collagen fibril and (ii) controlled release of platelet-derived growth factors (PDGFs) from the NPs. PDGF released from collagen-NP fibers significantly enhanced the proliferation of ADSCs when tested for up to 7 days. Moreover, compared to random collagen fibers with PDGFs, aligned collagen-NP fibers significantly promoted the desirable tenogenic differentiation of ADSCs, as evidenced by an increased level of tendon markers such as tenomodulin and scleraxis. On the other hand, no undesirable osteogenic differentiation, as measured by the unchanged level of alkaline phosphatase and osteocalcin, was observed. Together, these results indicate that the aligned collagen-NP composite fiber induced the tenogenic differentiation of ADSCs through both a topographic cue (aligned collagen fibril) and a chemical cue (PDGF released from NPs). Thus, our novel aligned collagen-NP composite fiber has a significant potential to be used for tendon tissue engineering and regeneration.