Cell Delivery System Research Articles

Development of drug and cell delivery system for active targeting based on magnetic liposomes

Development of drug and cell delivery system for active targeting based on magnetic liposomes

Blended, crosslinked alginate-methylcellulose hydrogels for encapsulation and delivery of olfactory ensheathing cells

Transplantation of olfactory ensheathing cells (OECs) is a promising treatment option for spinal cord injuries. Functional outcomes however are highly variable, creating the need for improved transplantation and cell delivery methods. Low OEC survival post-transplantation is primarily due to the absence of a 3D cell delivery system and scaffold, capable of supporting cell structure and migration at the injury site. A 3D cell delivery system, particularly a hydrogel-based system, could ensure viability, functionality and therapeutic activity of transplanted OECs. This study aimed to develop a blended cell delivery system based on alginate (AL) and methylcellulose (MC), capable of encapsulating and delivering OECs over a 20-day period. Three different 1 w/v% ALMC ratios (1:0.5, 1:1 and 1:2) were investigated, which were compared to 1 w/v% AL (control). By chemically crosslinking the pre-gels with CaCl2, OECs were encapsulated within the AL and blended ALMC beads. These beads were then used to study encapsulation efficiency (EE%) and cell delivery, and were further examined with histology and immunocytochemistry. Results showed that the blended ALMC hydrogel can be used to encapsulate OECs, with the highest EE% and cell proliferation exhibited by the 1:0.5 and 1:2 ALMC beads. The 1:1 and 1:2 ALMC beads showed the highest percentage viability for delivered/released and proliferating OECs. Examination of delivered/released OECs concluded that the cell morphology was characteristic of native bipolar OECs, which expressed signature glial markers, demonstrating maintenance of phenotype. In summary, the findings here support the efficacy and use of blended ALMC hydrogels as a cell delivery system.

Glutathione-Allylsulfur Conjugates as Mesenchymal Stem Cells Stimulating Agents for Potential Applications in Tissue Repair.

The endogenous gasotransmitter H2S plays an important role in the central nervous, respiratory and cardiovascular systems. Accordingly, slow-releasing H2S donors are powerful tools for basic studies and innovative pharmaco-therapeutic agents for cardiovascular and neurodegenerative diseases. Nonetheless, the effects of H2S-releasing agents on the growth of stem cells have not been fully investigated. H2S preconditioning can enhance mesenchymal stem cell survival after post-ischaemic myocardial implantation; therefore, stem cell therapy combined with H2S may be relevant in cell-based therapy for regenerative medicine. Here, we studied the effects of slow-releasing H2S agents on the cell growth and differentiation of cardiac Lin− Sca1+ human mesenchymal stem cells (cMSC) and on normal human dermal fibroblasts (NHDF). In particular, we investigated the effects of water-soluble GSH–garlic conjugates (GSGa) on cMSC compared to other H2S-releasing agents, such as Na2S and GYY4137. GSGa treatment of cMSC and NHDF increased their cell proliferation and migration in a concentration dependent manner with respect to the control. GSGa treatment promoted an upregulation of the expression of proteins involved in oxidative stress protection, cell–cell adhesion and commitment to differentiation. These results highlight the effects of H2S-natural donors as biochemical factors that promote MSC homing, increasing their safety profile and efficacy after transplantation, and the value of these donors in developing functional 3D-stem cell delivery systems for cardiac muscle tissue repair and regeneration.

Doxorubicin-Loaded Squid Pen Plaster: A Natural Drug Delivery System for Cancer Cells.

The native structure of the β-chitin in the gladius (squid pen) of Loligo vulgaris squid can be used as a natural plaster to entrap and release a model drug, doxorubicin, in a targeted and controlled way. Local pH determines the protonation state of the doxorubicin molecules, controlling the two phenomena. Confocal microscopy shows that doxorubicin is uniformly embedded in the β-chitin squid pen and is not simply adsorbed on its surface. Coculture with HeLa cells reveals that the β-chitin squid pen plaster is perfectly biocompatible, while when it is loaded with doxorubicin it shows high cytotoxicity toward the cancer cells. The drug, once released, rapidly accumulates inside the cells. In conclusion, the native structure of a β-chitin squid pen can be potentially applied as a "green" pH-responsive drug vehicle for controlled release.

Polymer-based porous microcarriers as cell delivery systems for applications in bone and cartilage tissue engineering

ABSTRACT For tissue regeneration or repair, a suitable temporary scaffold needs to be constructed for delivering regenerative cells to damaged or diseased tissue. Scaffold types are currently categorised into 3D monolithic scaffolds, hydrogels, and microcarriers. Among these scaffolds, microcarrier systems offer an attractive method for cell amplification and enhancement of phenotype expression, and they have emerged as powerful injectable carriers to repair and reconstruct irregular defects in tissues and organs. In this article, several important issues related to polymeric porous microcarriers for tissue engineering are reviewed. The properties of porous microcarriers, including surface chemistry, pore structure, typical particle size, and specific density, and the corresponding effects on cell cultures are discussed. The fabrication techniques and biomaterials investigated for porous microcarriers are summarised, and their advantages and disadvantages are outlined. Recent advancements in the application of porous microcarriers, including bone and cartilage tissue engineering, are also presented.

A photocaged DNA nanocapsule for delivery and manipulation in cells.

It is important to create new, specifically designed and controlled nanomaterials that can be used as molecular delivery systems for cells. Here, we describe a method for creating a nanosized DNA capsule (NC) using a photocaged unlocking system as a carrier for cell delivery. The photocaged NC (caged-NC) was designed and constructed to control the opening of the closed NC by photoirradiation. The opening of the NC was observed by atomic force microscopy, and the dynamic opening of the caged-NC was characterized by fluorescence quenching and recovery processes. The caged-NC was then introduced into the cytoplasm of a cell, where the photoinduced opening of the caged-NC was observed. The selective opening of the caged-NC in a single cell was successfully achieved by laser irradiation of individual cells. The caged-NC system could be used as a delivery system for relatively large nanomaterials in cells, similar to a native virus system.

Drug and Cell Delivery Systems for Posterior Ocular Diseases

Drug and Cell Delivery Systems for Posterior Ocular Diseases

Soy protein and chitin sponge-like scaffolds: from natural by-products to cell delivery systems for biomedical applications

Natural and renewable resources, such as plant proteins and marine polysaccharides, to manufacture scaffolds with suitable properties for biomedical applications.

Intrinsic Cellular Responses of Human Wharton's Jelly Mesenchymal Stem Cells Influenced by O2-Plasma-Modified and Unmodified Surface of Alkaline-Hydrolyzed 2D and 3D PCL Scaffolds.

Polycaprolactone (PCL), a hydrophobic-degradable polyester, has been widely investigated and extensively developed, to increase the biocompatibility for tissue engineering. This research was the first trial to evaluate the intrinsic biological responses of human Wharton’s Jelly Mesenchymal Stem Cells (hWJMSCs) cultured on alkaline hydrolysis and low-pressure oxygen plasma modified 2D and 3D PCL scaffolds, without adding any differentiation inducers; this has not been reported before. Four types of the substrate were newly established: 2D plasma-treated PCL (2D-TP), 2D non-plasma-treated PCL (2D-NP), 3D plasma-treated PCL (3D-TP), and 3D non-plasma-treated PCL (3D-NP). Physicochemical characterization revealed that only plasma-treated PCL scaffolds significantly increased the hydrophilicity and % oxygen/carbon ratio on the surfaces. The RMS roughness of 3D was higher than 2D conformation, whilst the plasma-treated surfaces were rougher than the non-plasma treated ones. The cytocompatibility test demonstrated that the 2D PCLs enhanced the initial cell attachment in comparison to the 3Ds, indicated by a higher expression of focal adhesion kinase. Meanwhile, the 3Ds promoted cell proliferation and migration as evidence of higher cyclin-A expression and filopodial protrusion, respectively. The 3Ds potentially protected the cell from apoptosis/necrosis but also altered the pluripotency/differentiation-related gene expression. In summary, the different configuration and surface properties of PCL scaffolds displayed the significant potential and effectiveness for facilitating stem cell growth and differentiation in vitro. The cell–substrate interactions on modified surface PCL may provide some information which could be further applied in substrate architecture for stem cell accommodation in cell delivery system for tissue repair.

PCL-MECM-Based Hydrogel Hybrid Scaffolds and Meniscal Fibrochondrocytes Promote Whole Meniscus Regeneration in a Rabbit Meniscectomy Model.

Regeneration of an injured meniscus continues to be a scientific challenge due to its poor self-healing potential. Tissue engineering provides an avenue for regenerating a severely damaged meniscus. In this study, we first investigated the superiority of five concentrations (0%, 0.5%, 1%, 2%, and 4%) of meniscus extracellular matrix (MECM)-based hydrogel in promoting cell proliferation and the matrix-forming phenotype of meniscal fibrochondrocytes (MFCs). We found that the 2% group strongly enhanced chondrogenic marker mRNA expression and cell proliferation compared to the other groups. Moreover, the 2% group showed the highest glycosaminoglycan (GAG) and collagen production by day 14. We then constructed a hybrid scaffold by 3D printing a wedge-shaped poly(ε-caprolactone) (PCL) scaffold as a backbone, followed by injection with the optimized MECM-based hydrogel (2%), which served as a cell delivery system. The hybrid scaffold (PCL-hydrogel) clearly yielded favorable biomechanical properties close to those of the native meniscus. Finally, PCL scaffold, PCL-hydrogel, and MFCs-loaded hybrid scaffold (PCL-hydrogel-MFCs) were implanted into the knee joints of New Zealand rabbits that underwent total medial meniscectomy. Six months postimplantation we found that the PCL-hydrogel-MFCs group exhibited markedly better gross appearance and cartilage protection than the PCL scaffold and PCL-hydrogel groups. Moreover, the regenerated menisci in the PCL-hydrogel-MFCs group had similar histological structures, biochemical contents, and biomechanical properties as the native menisci in the sham operation group. In conclusion, PCL-MECM-based hydrogel hybrid scaffold seeded with MFCs can successfully promote whole meniscus regeneration, and cell-loaded PCL-MECM-based hydrogel hybrid scaffold may be a promising strategy for meniscus regeneration in the future.

Hyaluronic Acid-Decorated Liposomes as Innovative Targeted Delivery System for Lung Fibrotic Cells.

Collagen Tissue Disease–associated Interstitial Lung Fibrosis (CTD-ILDs) and Bronchiolitis Obliterans Syndrome (BOS) represent severe lung fibrogenic disorders, characterized by fibro-proliferation with uncontrolled extracellular matrix deposition. Hyaluronic acid (HA) plays a key role in fibrosis with its specific receptor, CD44, overexpressed by CTD-ILD and BOS cells. The aim is to use HA-liposomes to develop an inhalatory treatment for these diseases. Liposomes with HA of two molecular weights were prepared and characterized. Targeting efficiency was assessed toward CTD-ILD and BOS cells by flow cytometry and confocal microscopy and immune modulation by RT-PCR and ELISA techniques. HA-liposomes were internalized by CTD-ILD and BOS cells expressing CD44, and this effect increased with higher HA MW. In THP-1 cells, HA-liposomes decreased pro-inflammatory cytokines IL-1β, IL-12, and anti-fibrotic VEGF transcripts but increased TGF-β mRNA. However, upon analyzing TGF-β release from healthy donors-derived monocytes, we found liposomes did not alter the release of active pro-fibrotic cytokine. All liposomes induced mild activation of neutrophils regardless of the presence of HA. HA liposomes could be also applied for lung fibrotic diseases, being endowed with low pro-inflammatory activity, and results confirmed that higher MW HA are associated to an increased targeting efficiency for CD44 expressing LFs-derived from BOS and CTD-ILD patients.

Novel mesenchymal stem cell delivery system as targeted therapy against neuroblastoma using the TH-MYCN mouse model

PurposeMesenchymal stem cells (MSCs) are reported to migrate toward damaged tissues or tumors. We previously reported the in vivo short-term (1 day) tumor-homing effect of xenogeneic human MSCs (hMSCs) using the TH-MYCN mouse neuroblastoma model (MYCN-TgM). In this study, we analyzed the long-term tumor-homing effect of allogeneic mouse MSCs (mMSCs) and explored the antitumor effect and drug delivery function of mMSCs. MethodsmMSCs were administered intraperitoneally (i.p.) to MYCN-TgM and traced by an in vivo imaging system (IVIS). We administered green fluorescent protein (GFP)-transduced mMSCs into MYCN-TgM i.p. and examined the cell survival by immunohistochemistry. We also administered interferon beta-transduced mMSCs (mMSCs-IFN-β) to MYCN-TgM i.p. and measured the concentration of IFN-β in the tumor and organs by an enzyme-linked immunosorbent assay (ELISA). The survival curves of MYCN-TgM administered every week was analyzed. ResultsThe IVIS revealed the accumulation of fluorescence was observed in the tumor both in vivo and after excision. Immunohistochemistry using anti-GFP antibody revealed that the mMSCs existed within the tumor until 14 days but not in the organs. The ELISA showed increased concentrations of IFN-β only in the tumors, with the values gradually diminishing over 14 days. The mMSCs-IFN-β group survived significantly longer than the control group (p < 0.03), while the mMSCs-alone group did not show a survival advantage. ConclusionsAllogeneic mMSCs showed a homing ability for mouse neuroblastoma and existed within the tumor for as long as two weeks. This may be a candidate drug delivery vehicle for antitumor agents against neuroblastoma.Level of evidence

Synergistic Enhancement of Cellular Uptake With CD44-Expressing Malignant Pleural Mesothelioma by Combining Cationic Liposome and Hyaluronic Acid–Lipid Conjugate

Malignant pleural mesothelioma (MPM) is a highly aggressive form of cancer, with a median survival of less than 1 year. It is well known that the hyaluronan (HA) receptor CD44 is highly expressed by MPM cells and is reported to be correlated with a poor prognosis. We herein report on the development of a new type if drug delivery system against CD44 that involves the use of lipid nanoparticles (LNPs) equipped with a new type of HA derivative. In this study, we evaluated HA-lipid conjugation (HAL) via the end of the HA molecule through reductive amination, a process that allowed the carboxylate group to remain intact. As a result, the HAL-modified LNP appears to be a potent nanoparticle for dealing with MPM. Surprisingly, the use of a combination of a cationic lipid and HAL had a synergistic effect on cellular uptake in MPM and consequently permitted an anti-cancer drug such as cis-diamminedichloro-platinum(II) (CDDP). Intrapleural injection of CDDP-loaded HAL-LNP (1.5 mg/kg as CDDP) per week significantly suppressed the progression of this type of cancer in an MPM orthotopic model. These results suggest that HAL-modified LNP represents a potent delivery system for MPM cells that express high levels of CD44.

Self-assembling peptide modified with QHREDGS as a novel delivery system for mesenchymal stem cell transplantation after myocardial infarction.

The lower cell survival and retention in the hostile microenvironment after transplantation has been implicated as a major bottleneck in the advancement of stem cell therapy for myocardial infarction (MI). In this study, we designed a novel self-assembling peptide (SAP) by attaching prosurvival peptide QHREDGS derived from angiopoeitin-1 to the known SAP, RADA16-I. The mesenchymal stem cells (MSCs) were harvested from male rats and cytoprotective effect of this designer SAP (DSAP) on cultured MSCs was detected by Hoechst 33342 staining after being exposed to oxygen and glucose deprivation (OGD). The cytoprotective effect of MSCs seeded in DSAP (DSAP-MSCs) on OGD treated cardiomyocytes was examined by TUNEL staining, phosphorylated (p-) protein kinase B (Akt) level, and ELISA. The therapeutic potential of MSC transplantation carried in DSAP was evaluated in a female rat MI model. PBS, MSCs alone, MSCs seeded in SAP (SAP-MSCs), or DSAP-MSCs were transplanted into the border of the infarcted area, respectively. DSAP not only increased the proliferation of MSCs and decreased apoptosis of MSCs after OGD treatment but also promoted the secretion of IGF-1 and HGF in MSCs. Treatment with culture supernatant of DSAP-MSCs markedly reduced the percentage of apoptotic cardiomyocytes and increased the level of p-Akt. Compared with the MSC group and SAP-MSC group, DSAP-MSC injection improved cardiac function and reduced infarct size, collagen content, and cell apoptosis. The number of Y chromosome-positive cells and microvessels in the DSAP-MSC group was higher than those in the MSC group and SAP-MSC group. Moreover, DSAP-MSC transplantation down-regulated the expression of IL-6 and IL-1β and up-regulated the level of VEGF and HGF. Interestingly, miR-21 was enriched in DSAP-MSC-derived exosomes (DSAP-MSC-Exos) and the protection against cardiomyocyte apoptosis by DSAP-MSC-Exos was inhibited when miR-21 was knocked down. Furthermore, miR-21 contributed to the improvement of cardiac function after DSAP-MSC-Exo injection in a rat model of MI. Additionally, the combination of DSAP and cardiotrophin-1 (Ctf1) pretreatment further improved the survival of MSCs and the efficiency of MSC transplantation. We proposed QHREDGS-modified SAP as an effective cell delivery system and demonstrated that MSC transplantation in this DSAP promoted angiogenesis and paracrine, thereby reducing scar size and cell apoptosis as well as improving cardiac function probably via exosome-mediated miR-21 after MI. Furthermore, for the first time, we proposed that DSAP, especially working together with Ctf1 pretreatment, could be a valuable way to improve the survival of MSCs and the efficiency of MSC transplantation after MI.-Cai, H., Wu, F.-Y., Wang, Q.-L., Xu, P., Mou, F.-F., Shao, S.-J., Luo, Z.-R., Zhu, J., Xuan, S.-S., Lu, R., Guo, H.-D. Self-assembling peptide modified with QHREDGS as a novel delivery system for mesenchymal stem cell transplantation after myocardial infarction.

Gelatin-based micro-hydrogel carrying genetically engineered human endothelial cells for neovascularization

Cell delivery systems based on micro-hydrogels may facilitate the long-term survival of cells upon transplantation. Micro-hydrogels may effectively support cell proliferation, attachment, and migration in ischemic environments. In this study, we report the fabrication of a gelatin methacrylate (GelMA)-based micro-hydrogel for efficient in vivo delivery of genetically engineered endothelial cells. Micro-hydrogels were initially processed via electrospraying of GelMA and alginate (ALG) mixtures (at different ratios) on to calcium chloride (CaCl2) solution. Electrospraying of the GelMA/ALG mixture resulted in the formation of a micro-hydrogel, owing to ALG crosslinking. Secondary crosslinking of GelMA with UV light and ALG hydrogel chelation using sodium citrate solution resulted in GelMA-based micro-hydrogel formation. We observed the angiogenic response of human umbilical vein endothelial cells (HUVECs) in GelMA concentration-dependent manner. The seeding of HUVECs engineered to express human vascular endothelial growth factor on to the GelMA micro-hydrogel and the subsequent transplantation of the micro-hydrogel into a hindlimb ischemia model effectively attenuated the ischemia condition. This facile and simple micro-hydrogel fabrication strategy may serve as a robust method to fabricate efficient cell carriers for various ischemic diseases. Statement of SignificanceFor the therapeutic angiogenesis, it is important to provide the therapeutic cells with a carrier that could stabilize therapeutic cells and facilitate long-term survival of cells. Furthermore, it is also important to administer as many therapeutic cells as possible in a fixed volume. From these cues, we fabricated ECM-based micro-hydrogel produced by the high through-put system. And we intended to facilitate activation of therapeutic cells by coating the therapeutic cells onto the micro-hydrogel. In this manuscript, we fabricated methacrylate gelatin (GelMA) based micro-hydrogels using the electro-spraying method and coated HUVECs engineered to express hVEGF onto the micro-hydrogels. Then, we identified that GelMA concentration-dependent angiogenic response of HUVECs. Furthermore, we demonstrated that the VEGF secreting HUVEC-GelMA micro-hydrogels induced the restoration of blood flow and neovascularization in a hind-limb ischemia mouse model. These findings demonstrate that the high-throughput fabrication of ECM micro-hydrogels could be a novel platform to apply in neovascularization and tissue engineering.

Controllable fabrication of hydroxybutyl chitosan/oxidized chondroitin sulfate hydrogels by 3D bioprinting technique for cartilage tissue engineering

Biological regeneration of articular cartilage continues to be a challenge at present. Functional engineered implants with patient-specific sizes are difficult to achieve. The aim of this study is to fabricate a biocompatible cell-laden hydrogel with a designable structure. Covalent hydrogels were prepared with water soluble hydroxybutyl chitosan (HBC) and oxidized chondroitin sulfate (OCS) via a Schiff-base reaction. With the aid of three-dimensional (3D) bioprinted sacrificial molds, HBC/OCS hydrogel with various structures were obtained. After the material constituent optimization process, an injectable hydrogel with a uniform porous structure of 100 μm average pore size was developed to form macroporous hydrogel. In vitro and in vivo biocompatibility of optimized HBC/OCS hydrogel were also carefully assessed. The results indicated that human adipose-derived mesenchymal stem cells could be 3D cultured in HBC/OCS hydrogel maintaining good viability. Moreover, the hydrogels were found to trigger the least amount of pro-inflammatory gene expression of macrophage and to inhibit acute immune responses in 7 d. These results demonstrate the potential of HBC/OCS hydrogels as a cell delivery system for cartilage tissue engineering.

Use of a Sendai virus-based vector for effcient transduction of pinniped fbroblasts

Generation of induced pluripotent stem (iPS) cells expanded possibilities of pluripotency and early development studies. Generation of order Carnivora iPS cells from dog (Canis lupus familiaris), snow leopard (Panthera uncia), and American mink (Neovison vison) was previously reported. The aim of the current study was to examine conditions of pinniped fbroblast reprogramming. Pinnipeds are representatives of the suborder Caniformia sharing conservative genomes. There are several ways to deliver reprogramming transcription factors: RNA, proteins, plasmids, viral vectors etc. The most effective delivery systems for mouse and human cells are based on viral vectors. We compared a lentiviral vector which integrates into the genome and a Sendai virus­based vector, CytoTune EmGFP Sendai Fluorescence Reporter. The main advantage of Sendai virus­based vectors is that they do not integrate into the genome. We performed delivery of genetic constructions carrying fluorescent proteins to fbroblasts of seven Pinnipeds: northern fur seal (Callorhinus ursinus), Steller sea lion (Eumetopias jubatus), walrus (Odobenus rosmarus), bearded seal (Erignathus barbatus), Baikal seal (Pusa sibirica), ringed seal (Phoca hispida), and spotted seal (Phoca largha). We also transduced American mink (N. vison), human (Homo sapiens), and mouse (Mus musculus) fbroblasts as a control. We showed that the Sendai virus­based transduction system provides transgene expression one­two orders of magnitude higher than the lentiviral system at a comparable multiplicity of infection. Also, transgene expression after Sendai virus­based transduction is quite stable and changes only slightly at day four compared to day two. These data allow us to suggest that Sendai virus­based vectors are preferable for generation of Pinniped iPS cells.

Enhanced macrophage delivery to the colon using magnetic lipoplexes with a magnetic field

Magnetically guided cell delivery systems would be valuable to achieve effective macrophage-based cell therapy for colonic inflammatory diseases. In the current study, we developed a method for the efficient and simultaneous introduction of superparamagnetic iron oxide nanoparticles (SPIONs) and plasmid DNA (pDNA) into RAW264 murine macrophage-like cells using SPION-incorporated cationic liposome/pDNA complexes (magnetic lipoplexes). SPIONs and pDNA were introduced for magnetization and functionalization of the macrophages, respectively. We also evaluated the adhesive properties of magnetized RAW264 cells using magnetic lipoplexes in the murine colon under a magnetic field. Significant cellular association and gene expression without cytotoxicity were observed when magnetic cationic liposomes and pDNA were mixed at a weight ratio of 10:1, and SPION concentration and magnetic field exposure time was 0.1 mg/mL and 10 min, respectively. We also observed that cytokine production in magnetized RAW264 cells was similar to that in non-treated RAW264 cells, whereas nitric oxide production was significantly increased in magnetized RAW264 cells. Furthermore, magnetized RAW264 cells highly adhered to a Caco-2 cell monolayer and colon in mice, under a magnetic field. These results suggest that this magnetic cell delivery system can improve the colonic delivery of macrophages and its therapeutic efficacy against colonic inflammatory diseases.

Regenerative Medicine: Injectable Cell-Based Therapeutics and Approved Products.

Cellular-based therapies have drawn a great deal of attention thanks to their regenerative medicine approaches to treat incurable diseases and specific injuries. In this regard, injectable cell delivery systems could actualize the therapeutically beneficial outcomes of cell-based therapeutic products. These systems have found considerable clinical uses. Hence, the recent studies have focused on developing injectable bio-constructs to protect transplanted cells during delivery and stimulating endogenous regeneration through interactions of these cells and host tissue. This paper introduces a framework, as a general concept, to improve cell delivery systems for cell-based therapeutic products. Studies on stable injectable carriers can enhance cell homing, proliferation, viability, dressing of irregular shape of target sites, and subsequently support transplanted cell functionality. However, more studies should be conducted on new technologies for the injectable cell-based product for cell delivery and the clinical applications.

Periodontal healing using a collagen matrix with periodontal ligament progenitor cells in a dehiscence defect model in beagle dogs.

PurposeTo histologically characterize periodontal healing at 8 weeks in surgically created dehiscence defects in beagle dogs that received a collagen matrix with periodontal ligament (PDL) progenitor cells.MethodsThe bilateral maxillary premolars and first molars in 6 animals were used. Standardized experimental dehiscence defects were made on the buccal side of 3 premolars, and primary culturing of PDL progenitor cells was performed on the molars. Collagen matrix was used as a scaffold and a delivery system for PDL progenitor cells. The experimental sites were grafted with collagen matrix (COL), PDL progenitor cells with collagen matrix (COL/CELL), or left without any material (CTL). Histologic and histomorphometric analyses were performed after 8 weeks.ResultsThe defect height from the cementoenamel junction to the most apical point of cementum removal did not significantly differ across the CTL, COL, and COL/CELL groups, at 4.57±0.28, 4.56±0.41, and 4.64±0.27 mm (mean ± standard deviation), respectively; the corresponding values for epithelial adhesion were 1.41±0.51, 0.85±0.29, and 0.30±0.41 mm (P<0.05), the heights of new bone regeneration were 1.32±0.44, 1.65±0.52, and 1.93±0.61 mm (P<0.05), and the cementum regeneration values were 1.15±0.42, 1.81±0.46, and 2.57±0.56 mm (P<0.05). There was significantly more new bone formation in the COL/CELL group than in the CTL group, and new cementum length was also significantly higher in the COL/CELL group. However, there were no significant differences in the width of new cementum among the groups.ConclusionsPDL progenitor cells carried by a synthetic collagen matrix may enhance periodontal regeneration, including cementum and new bone formation.