Restoration of rat calvarial defects by poly(lactide-co-glycolide)/hydroxyapatite scaffolds loaded with bone mesenchymal stem cells and DNA complexes

Li, Dan; Wang, Wei; Guo, Rui; Qi, Yiying; Gou, Zhongru; Gao, Changyou

doi:10.1007/s11434-011-4914-0

Cited by 10 publications

(9 citation statements)

References 36 publications

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“…Setting the joint site as an example, this site exhibits less host responses to implant, because more body fluids and faster fluid exchange are helpful for removing the acidic degradation products effectively. In fact, many positive results of tissue repairing using PLA or PLGA porous scaffolds have been reported [27][28][29][30]48,49]. Our group has recently revealed that the body fluid exchanged faster than we initially supposed, even at the subcutaneous site, for a block copolymer hydrogel composed of PLGA-PEG-PLGA with initial pH 4 became neutral just ten hours after a subcutaneous injection into SD rats [50].…”

Section: Is There Any Significant Difference Of Cytotoxicity Between mentioning

confidence: 93%

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Effects of L-lactic acid and D,L-lactic acid on viability and osteogenic differentiation of mesenchymal stem cells

Wang

Ding

2013

Chin. Sci. Bull.

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Poly(lactic acid) (PLA) and other aliphatic polyesters containing the unit of lactic acid are very popular biodegradable materials. While the degradation products, lactic acids, have been worried to bring with negative influence on biocompatibility, the focused experimental studies are less reported. This study is aimed at an in vitro examination of cytotoxicity of both L-lactic acid and D,L-lactic acid. Mesenchymal stem cells (MSCs) derived from rat bone marrow are employed to test the cytotoxicity of the lactic acids. Considering that the addition of lactic acids not only introduces lactate groups but also alters medium pH and ion strength, these three candidate effects are examined in a decoupled way by setting different comparison groups. The results confirm that the change of medium pH is the predominant factor. It has also been found that D-lactate is more cytotoxic than L-lactate at high concentrations. Yet, either L-or D,L-lactic acids seem acceptable in most of medical applications, because the cytotoxicity is significant only when the concentrations are as high as 20 mmol/L for both of them.

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Section: Is There Any Significant Difference Of Cytotoxicity Between mentioning

confidence: 93%

“…That is why polyesters have been studied for a long time [14][15][16][17][18][19][20]. A lot of efforts have been done on improving the biocompatibility of the polyester porous scaffolds [21][22][23][24][25][26][27][28], and examinations of their medical applications [27][28][29][30][31][32][33].…”

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confidence: 99%

Effects of L-lactic acid and D,L-lactic acid on viability and osteogenic differentiation of mesenchymal stem cells

Wang

Ding

2013

Chin. Sci. Bull.

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“…In one study, PEI25 was beneficial when pDNA was delivered in scaffolds in a cranial defect site . Other studies with sustained release formulations or a carrier functional in vitro ( N,N,N ‐trimethyl chitosan) did not result in improved bone formation in a similar intracranial site. It remains to be seen whether the scaffold effects (chemical composition, physical architecture controlling cell invasion, degradation products, etc.)…”

Section: Pharmacokinetics and Pharmacodynamics Of Gene Deliverymentioning

confidence: 99%

Realizing the potential of gene-based molecular therapies in bone repair

Rose

Uludağ

2013

Journal of Bone and Mineral Research

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A better understanding of osteogenesis at genetic and biochemical levels is yielding new molecular entities that can modulate bone regeneration and potentially act as novel therapies in a clinical setting. These new entities are motivating alternative approaches for bone repair by utilizing DNA-derived expression systems, as well as RNA-based regulatory molecules controlling the fate of cells involved in osteogenesis. These sophisticated mediators of osteogenesis, however, pose unique delivery challenges that are not obvious in deployment of conventional therapeutic agents. Viral and nonviral delivery systems are actively pursued in preclinical animal models to realize the potential of the gene-based medicines. This article will summarize promising bone-inducing molecular agents on the horizon as well as provide a critical review of delivery systems employed for their administration. Special attention was paid to synthetic (nonviral) delivery systems because they are more likely to be adopted for clinical testing because of safety considerations. We present a comparative analysis of dose-response relationships, as well as pharmacokinetic and pharmacodynamic features of various approaches, with the purpose of clearly defining the current frontier in the field. We conclude with the authors' perspective on the future of genebased therapy of bone defects, articulating promising research avenues to advance the field of clinical bone repair. © 2013 American Society for Bone and Mineral Research. KEY WORDS: OSTEOGENESIS; BIOENGINEERING; MOLECULAR PATHWAYS; GENE-BASED THERAPYClinical Need for New Bone-Regeneration Strategies N early 2.2 million bone grafts are performed worldwide annually (1) and up to 20% of fractures are hampered by impaired healing. (2) The economic impact of nonunions is enormous, with the cost of spinal fusions alone reaching $20 billion annually. (3) The gold standard for repair of large segmental defects remains autologous grafts, where bone harvested from a non-weight-bearing site, usually the iliac crest, is used to repair defects. Bone grafts, however, are limited in several aspects, including potency of the grafts and the physiological detriment resulting from harvest surgery. Allografts are alternatively employed, where donor tissue is used to repair the defect, but the risk of disease transmission is always a concern. Allografts are extensively processed to reduce this risk, but osteopotency of the graft could be decreased in this way. (4) Demineralized bone matrix derived from decalcified bone can similarly act as a substitute; its potency, however, is variable and depends on the processing conditions. Synthetic scaffolds have been used to provide a hospitable environment for new bone formation. Scaffolds have been constructed from the organic (collagen) and inorganic (hydroxyapatite [HA]) components of bone, but such scaffolds are incapable of inducing osteogenesis on their own and they are more suitable for smaller defects.Osteogenic proteins are frequently employed to render ost...

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“…In our previous study, a hybrid scaffold of fibrin gel and PLGA sponge was proposed to act as a biomimetic tissue platform for cartilage regeneration . The porous sponges own the ease for processing and can supply comparable mechanical strength with the cartilage tissue. − However, the sponge alone is not competent to provide inductive signals for cell differentiation. The hydrogels are favorable for cell survival, proliferation, and differentiation, yet they have a rather weak mechanical strength. , The hybrids composed of sponges and hydrogels may overcome the disadvantages of each type of scaffold.…”

Section: Introductionmentioning

confidence: 99%

Poly(lactide-co-glycolide)/Fibrin Gel Construct as a 3D Model to Evaluate Gene Therapy of Cartilage in Vivo

et al. 2014

Mol. Pharmaceutics

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Combination of gene therapy with tissue engineering can enhance the interplay between cells and matrix, leading to better restoration and regeneration of tissues and organs in vivo. In this study the PLGA/fibrin gel hybrids were employed to load lipofectamine/pDNA-TGF-β1 complexes and mesenchymal stem cells (MSCs) (experimental group), acting as a cartilage-mimetic tissue platform. The gene complexes distributed more evenly in the hybrid scaffolds, whereas they adhered onto the pore walls of the PLGA sponges. The filled fibrin gel rendered gene release in a slower manner, too. Moreover, the fibrin gel entrapped MSCs and contributed to a higher cell loading density in the hybrid constructs. In vivo assay showed that in the defects implanted with the experimental constructs both gene and protein expression levels of TGF-β1 were significantly higher than those of the fibrin-free group at weeks 1, 3, and 6 after surgery. The full articular cartilage defects repaired by the experimental group for 12 w were resurfaced by neo-tissues with a similar thickness, cell arrangement, and color to the normal neighboring cartilage and abundant glycosaminoglycans.

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Restoration of rat calvarial defects by poly(lactide-co-glycolide)/hydroxyapatite scaffolds loaded with bone mesenchymal stem cells and DNA complexes

Cited by 10 publications

References 36 publications

Effects of L-lactic acid and D,L-lactic acid on viability and osteogenic differentiation of mesenchymal stem cells

Effects of L-lactic acid and D,L-lactic acid on viability and osteogenic differentiation of mesenchymal stem cells

Realizing the potential of gene-based molecular therapies in bone repair

Poly(lactide-co-glycolide)/Fibrin Gel Construct as a 3D Model to Evaluate Gene Therapy of Cartilage in Vivo

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