Dataset Information

Matrix elasticity-modified scaffold loaded with SDF-1? improves the in situ regeneration of segmental bone defect in rabbit radius.

ABSTRACT: The effectiveness of stem-cell based therapy has been hampered by the limited availability of stem cell sources, immune rejection, and difficulties in clinical adoption and regulatory approval. These obstacles can be partially circumvented by using in situ tissue engineering that recruits the endogenous stem/progenitor cells and provides cues to direct stem cell phenotype. Here, decellularized bone scaffold is mechanically modified by coating of collagen (Col)/hydroxyapatite (HA) mixture with optimal ratio and loaded with chemokine stromal cell-derived factor-1? (SDF-1?), in which endogenous stem cell recruitment can be improved by chemokine and stem cell fate can be regulated by matrix elasticity of the scaffold. This study shows that mesenchymal stem cells (MSCs) osteogenesis in vitro was enhanced by matrix elasticity and SDF-1?, and endogenous MSCs recruitment in subcutaneous implantation of rat was increased by the release of SDF-1? from the scaffold, and bone regeneration in rabbit large bone defect model was significantly improved by matrix elasticity and SDF-1?. In short, this study provides a new insight for developing novel engineered cell-free bone substitutes by mechanical modification for tissue engineering and regenerative medicine.

SUBMITTER: Chen G

PROVIDER: S-EPMC5432001 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Matrix elasticity-modified scaffold loaded with SDF-1α improves the in situ regeneration of segmental bone defect in rabbit radius.

Chen Guobao G Lv Yonggang Y

Scientific reports 20170510 1

The effectiveness of stem-cell based therapy has been hampered by the limited availability of stem cell sources, immune rejection, and difficulties in clinical adoption and regulatory approval. These obstacles can be partially circumvented by using in situ tissue engineering that recruits the endogenous stem/progenitor cells and provides cues to direct stem cell phenotype. Here, decellularized bone scaffold is mechanically modified by coating of collagen (Col)/hydroxyapatite (HA) mixture with op ...[more]

PMID: 28490814

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Project description:Self-fitting scaffolds prepared from biodegradable poly(ε-caprolactone)-diacrylate (PCL-DA) have been developed for the treatment of craniomaxillofacial (CMF) bone defects. As a thermoresponsive shape memory polymer (SMP), with the mere exposure to warm saline, these porous scaffolds achieve a conformal fit in defects. This behavior was expected to be advantageous to osseointegration and thus bone healing. Herein, for an initial assessment of their regenerative potential, a pilot in vivo study was performed using a rabbit calvarial defect model. Exogenous growth factors and cells were excluded from the scaffolds. Key scaffold material properties were confirmed to be maintained following gamma sterilization. To assess scaffold integration and neotissue infiltration along the defect perimeter, non-critically sized (d = 8 mm) bilateral calvarial defects were created in 12 New Zealand white rabbits. Bone formation was assessed at 4 and 16 weeks using histological analysis and micro-CT, comparing defects treated with an SMP scaffold (d = 9 mm x t = 1 or 2 mm) to untreated defects (i.e. defects able to heal without intervention). To further assess osseointegration, push-out tests were performed at 16 weeks and compared to defects treated with poly(ether ether ketone) (PEEK) discs (d = 8.5 mm x t = 2 mm). The results of this study confirmed that the SMP scaffolds were biocompatible and highly conducive to bone formation and ingrowth at the perimeter. Ultimately, this resulted in similar bone volume and surface area versus untreated defects and superior performance in push-out testing versus defects treated with PEEK discs. STATEMENT OF SIGNIFICANCE: Current treatments of craniomaxillofacial (CMF) bone defects include biologic and synthetic grafts but they are limited in their ability to form good contact with adjacent tissue. A regenerative engineering approach using a biologic-free scaffold able to achieve conformal fitting represents a potential "off-the-shelf" surgical product to heal CMF bone defects. Having not yet been evaluated in vivo, this study provided the preliminary assessment of the bone healing potential of self-fitting PCL scaffolds using a rabbit calvarial defect model. The study was designed to assess scaffold biocompatibility as well as bone formation and ingrowth using histology, micro-CT, and biomechanical push-out tests. The favorable results provide a basis to pursue establishing self-fitting scaffolds as a treatment option for CMF defects.

Project description:BackgroundThe control of endothelial progenitor cells (CD133+/CD34+ EPCs) migrating from bone marrow to peripheral blood is not completely understood. Emerging evidence suggests that stromal cell-derived factor-1α (SDF-1α) mediates egression of EPCs from bone marrow, while the hypoxia inducible factor (HIF) transcriptional system regulates SDF-1α expression. Our study aimed to investigate the time course of circulating CD133+/CD34+ EPCs and its correlation with the expression of HIF-1α protein and SDF-1α in postoperative laparoscopic abdominal septic patients.MethodsPostoperative patients were divided in control (C group) and septic group (S group) operated immediately after the diagnosis of sepsis/septic shock. Blood samples were collected at baseline (0), 1, 3 and 7 postoperative days for CD133+/CD34+ EPCs count expressing or not the HIF-1α and SDF-1α analysis.ResultsThirty-two patients in S group and 39 in C group were analyzed. In C group CD133+/CD34+ EPCs count remained stable throughout the study period, increasing on day 7 (173 [0-421] /μl vs baseline: P = 0.04; vs day 1: P = 0.002). In S group CD133+/CD34+ EPCs count levels were higher on day 3 (vs day 1: P = 0.006 and day 7: P = 0.026). HIF-1α expressing CD133+/CD34+ EPCs count decreased on day 1 as compared with the other days in C group (day 0 vs 1: P = 0.003, days 3 and 7 vs 1: P = 0.008), while it was 321 [0-1418] /μl on day 3 (vs day 1; P = 0.004), and 400 [0-587] /μl on day 7 in S group. SDF-1α levels were higher not only on baseline but also on postoperative day 1 in S vs C group (219 [124-337] pg/ml vs 35 [27-325] pg/ml, respectively; P = 0.01).ConclusionOur results indicate that sepsis in abdominal laparoscopic patients might constitute an additional trigger of the EPCs mobilization as compared with non-septic surgical patients. A larger mobilization of CD133+/CD34+ EPCs, preceded by enhanced plasmatic SDF-1α, occurs in septic surgical patients regardless of HIF-1α expression therein.Trial registrationClinicalTrials.gov no. NCT02589535 . Registered 28 October 2015.

Dataset Information

Matrix elasticity-modified scaffold loaded with SDF-1? improves the in situ regeneration of segmental bone defect in rabbit radius.

Publications

Matrix elasticity-modified scaffold loaded with SDF-1α improves the in situ regeneration of segmental bone defect in rabbit radius.

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