Doctor of Philosophy, University of South Carolina (2010)
Yunzhi Peter Yang, Postdoctoral Faculty Sponsor
View details for DOI 10.1002/term.1487
This study evaluated whether the combination of biodegradable β-tricalcium phosphate (β-TCP) scaffolds with recombinant human bone morphogenetic protein-2 (rhBMP-2) or platelet-rich plasma (PRP) could accelerate bone formation and increase bone height using a rabbit non-through cranial bone defect model. Four non-through cylindrical bone defects with a diameter of 8-mm were surgically created on the cranium of rabbits. β-TCP scaffolds in the presence and absence of impregnated rhBMP-2 or PRP were placed into the defects. At 8 and 16 weeks after implantation, samples were dissected and fixed for analysis by microcomputed tomography and histology. Only defects with rhBMP-2 impregnated β-TCP scaffolds showed significantly enhanced bone formation compared to non-impregnated β-TCP scaffolds (P < 0.05). Although new bone was higher than adjacent bone at 8 weeks after implantation, vertical bone augmentation was not observed at 16 weeks after implantation, probably due to scaffold resorption occurring concurrently with new bone formation.
View details for DOI 10.1007/s10856-013-4939-9
View details for Web of Science ID 000321915300008
View details for PubMedID 23779152
The objective of this work was to compare the release characteristics of Recombinant human bone morphogenetic protein-2 (rhBMP-2) encapsulated in thermally self-assembled poly(lactide ethylene oxide fumarate) (PLEOF) nanoparticles (NPs) with rhBMP-2 grafted to succinimide-terminated poly(lactide fumarate) (PLAF-NHS) or poly(lactide-co-glycolide fumarate) (PLGF-NHS) NPs. The amphiphilic PLEOF NPs had average size of 110 +/- 50 nm. The hydrophobic PLAF-NHS and PLGF-NHS NPs had average size of 242 +/- 67 and 195 +/- 42 nm, respectively. PLEOF NPs had rhBMP-2 encapsulation efficiency ranging from 65 to 93%. Grafting efficiency of rhBMP-2 to PLAF-NHS and PLGF-NHS NPs was 97% +/- 1% and 98% +/- 1%, respectively. PLEOF NPs displayed a relatively high-release rate of rhBMP-2 in the first week, which rapidly dropped to zero after 10 days. PLEOF NPs grafted with 10 and 20 microg/mL rhBMP-2 released 67 and 80% of the protein in the active conformation after degradation. PLGF-NHS NPs displayed sustained release of rhBMP-2 in the first 2 weeks but dropped to almost zero rate (< 3 ng/day) after 20 days. PLAF-NHS NPs showed the longest period of sustained release of active rhBMP-2 at two rates: a high rate of 25-35 ng/mL in the first 2 weeks followed by a low rate of 5-10 ng/mL from 2 to 6 weeks. Nearly, 25 and 50% of the rhBMP-2 released from PLGF-NHS and PLAF-NHS NPs, respectively, were enzymatically active after degradation of the NPs. PLEOF NPs provided a fast release of rhBMP-2 for 1 week, whereas PLAF-NHS NPs provided a slow release for up to 6 weeks.
View details for DOI 10.1002/jemt.20846
View details for Web of Science ID 000282262800003
View details for PubMedID 20232367
Functionalized biodegradable nanoparticles (NPs) provide reactive groups and large surface area for grafting recombinant human bone morphogenetic protein-2 (rhBMP-2) to reduce protein diffusion and maintain sufficient concentration for recruitment and differentiation of osteoprogenitor cells. The objective of this work was to investigate release characteristics and osteogenic activity of rhBMP-2, grafted to biodegradable NPs based on succinimide-terminated poly(lactide fumarate) (PLAF-NHS) and poly(lactide-co-glycolide fumarate) (PLGF-NHS) macromers. The release of rhBMP-2 from the NPs, measured by enzyme-linked immunosorbent assay, was linear with time in the first two weeks, and 24.70+/-1.30% and 48.7+/-0.7% of the protein grafted to PLGF-NHS and PLAF-NHS NPs, respectively, was released in the enzymatically active conformation after complete degradation/erosion of the NPs. After 14 days of incubation with bone marrow stromal (BMS) cells, rhBMP-2 grafted to PLAF-NHS and PLGF-NHS NPs was as effective in inducing mineralization as the native rhBMP-2 that was directly added to the cell culture media. At any incubation time, rhBMP-2 grafted to PLAF had the highest expression of osteopontin (OP) and osteocalcin (OC), followed by rhBMP-2 grafted to PLGF and rhBMP-2 directly added to media. Higher OP and OC expression for BMP-gPLAF and BMP-gPLGF groups may be related to other factors in the cascade of osteogenesis, such as differentiation of BMS cells to the vasculogenic lineage and formation of a vascularized/mineralized matrix.
View details for DOI 10.1016/j.jconrel.2009.08.009
View details for Web of Science ID 000272497900011
View details for PubMedID 19699244
Lactide-co-glycolide-based functionalized nanoparticles (NPs), because of their high surface areas for conjugation and biodegradability, are attractive as carriers for stabilization and sustained delivery of therapeutic agents and protein drugs. The objective of this work was to compare the release characteristics of model molecules encapsulated in NPs produced from poly(lactide-co-glycolide fumarate) (PLGF) macromer with those of model molecules conjugated to NPs produced from succinimide (NHS)-terminated PLGF-NHS macromer. Poly(lactide fumarate) (PLAF), PLGF and poly(lactide-co-ethylene oxide fumarate) (PLEOF) macromers were synthesized by condensation polymerization. The hydroxyl end-groups of PLAF and PLGF macromers were reacted with N,N(')-disuccinimidyl carbonate (DSC) to produce succinimide-terminated PLAF-NHS and PLGF-NHS macromers. The macromers were self-assembled by dialysis to form NPs. The amphiphilic PLEOF macromer was used as the surfactant to stabilize the NPs in the process of self-assembly. 1-(2-pyridylazo)-2-naphthol (PAN) was used as a model small molecule for encapsulation in PLAF or PLGF NPs and bovine serum albumin (BSA) was used as a model protein for conjugation to PLAF-NHS and PLGF-NHS NPs. The profile of release of the encapsulated PAN from PLAF and PLGF NPs was non-linear and consisted of a burst release followed by a period of sustained release. The release profile for BSA, conjugated to PLAF-NHS and PLGF-NHS NPs, was linear up to complete degradation of the NPs. PLGF and PLAF NPs degraded in 15 and 28 days, respectively, while PLGF-NHS and PLAF-NHS NPs degraded in 25 and 38 days, which demonstrated that the release was dominated by erosion of the matrix. PLAF-NHS and PLGF-NHS NPs are potentially useful as carriers for sustained in situ release of protein drugs.
View details for DOI 10.1088/0957-4484/19/32/325609
View details for Web of Science ID 000257370600018
View details for PubMedID 21828822
Biodegradable core-shell polymeric nanoparticles (NPs), with a hydrophobic core and hydrophilic shell, are developed for surfactant-free encapsulation and delivery of Paclitaxel to tumor cells.Poly (lactide-co-glycolide fumarate) (PLGF) and Poly (lactide-fumarate) (PLAF) were synthesized by condensation polymerization of ultra-low molecular weight poly(L: -lactide-co-glycolide) (ULMW PLGA) with fumaryl chloride (FuCl). Similarly, poly(lactide-co-ethylene oxide fumarate) (PLEOF) macromer was synthesized by reacting ultra-low molecular weight poly(L: -lactide) (ULMW PLA) and PEG with FuCl. The blend PLGF/PLEOF and PLAF/PLEOF macromers were self-assembled into NPs by dialysis. The NPs were characterized with respect to particle size distribution, morphology, and loading efficiency. The physical state and miscibility of Paclitaxel in NPs were characterized by differential scanning calorimetry. Tumor cell uptake and cytotoxicity of Paclitaxel loaded NPs were measured by incubation with HCT116 human colon carcinoma cells. The distribution of NPs in vivo was assessed with Apc(Min/+)mouse using infrared imaging.PLEOF macromer, due to its amphiphilic nature, acted as a surface active agent in the process of self-assembly which produced core-shell NPs with PLGF/PLAF and PLEOF macromers as the core and shell, respectively. The encapsulation efficiency ranged from 70 to 56% and it was independent of the macromer but decreased with increasing concentration of Paclitaxel. Most of the PLGF and PLAF NPs degraded in 15 and 28 days, respectively, which demonstrated that the release was dominated by hydrolytic degradation and erosion of the matrix. As the concentration of Paclitaxel was increased from 0 to 10, and 40 mug/ml, the viability of HCT116 cells incubated with free Paclitaxel decreased from 100 to 65 and 40%, respectively, while those encapsulated in PLGF/PLEOF NPs decreased from 93 to 54 and 28%.Groups with Paclitaxel loaded NPs had higher cytotoxicity compared to Paclitaxel directly added to the media at the same concentration. NPs acted as reservoirs to protect the drug from epimerization and hydrolysis while providing a sustained dose of Paclitaxel with time. Infrared image of the Apc(Min/+) mouse injected with NPs showed significantly higher concentration of NPs in the intestinal tissue.
View details for DOI 10.1007/s11095-007-9513-z
View details for Web of Science ID 000256435200007
View details for PubMedID 18196205