Mesenchymal stem cell expression of SDF-1βsynergizes with BMP-2 to augment cell-mediated healing of critical-sized mouse calvarial defects

Abstract

Bone has the potential for spontaneous healing. This process, however, often fails in patients with comorbidities. Tissue engineering combining functional cells, biomaterials and osteoinductive cues may provide alternative treatment strategies. We have recently demonstrated that stromal cell-derived factor-1β (SDF-1β) works in concert with bone morphogenetic protein-2 (BMP-2) to potentiate osteogenic differentiation of bone marrow-derived mesenchymal stem/stromal cells (BMSCs). Here, we test the hypothesis that SDF-1β overexpressed in Tet-Off-SDF-1β BMSCs, delivered on acellular dermal matrix (ADM), synergistically augments BMP-2-induced healing of critical-sized mouse calvarial defects. BMSC therapies alone showed limited bone healing, which was increased with co-delivery of BMP-2. This was further enhanced in Tet-Off-SDF-1β BMSCs + BMP-2. Only limited BMSC retention on ADM constructs was observed after 4 weeks in vivo, which was increased with BMP-2 co-delivery. In vitro cell proliferation studies showed that supplementing BMP-2 to Tet-Off BMSCs significantly increased the cell number during the first 24 h. Consequently, the increased cell numbers decreased the detectable BMP-2 levels in the medium, but increased cell-associated BMP-2. The data suggest that SDF-1β provides synergistic effects supporting BMP-2-induced, BMSC-mediated bone formation and appears suitable for optimization of bone augmentation in combination therapy protocols.

Selective serotonin re-uptake inhibitor sertraline inhibits bone healing in a calvarial defect model

“…29 Briefly, calvarial specimens were radiographed using a Faxitron X-Ray imaging instrument (Faxitron X-Ray, Wheeling, IL, USA) and PPL film (Carestream, NY, USA) following initial calibration. Percent bone healing was estimated utilizing a 5.0-mm region of interest (ROI).…”

Involvement of calvarial stem cells in healing: A regional analysis of large cranial defects

“…One current option for augmentation of bone healing utilized heavily in the fields of orthopedic and craniofacial surgery is the use of an acellular collagen sponge (ACS) in combination with FDA‐approved bone morphogenic protein 2 (BMP2; INFUSE Bone Graft; Medtronic, Minneapolis, MN). BMP2 is an osteogenic peptide appearing to have a synergistic effect with endogenous osteogenic signaling . In this study, we aimed to determine what factors play a role in the healing process by using a regional analysis of a murine critical sized defect treated with an osteoconductive scaffold (ASC) and a clinically relevant dose of BMP2 .…”

Optimizing bone wound healing using BMP2 with absorbable collagen sponge and Talymed nanofiber scaffold

“…Under sterile conditions, 6 mm biopsy punches of ACS and 5 mm biopsy punches of Talymed were obtained and stored in a 24 well plate lined with sterile gauze. Fifteen minutes prior to implantation, matrices were loaded with BMP2 resuspended in 25 µl sterile water (Infuse, Medtronic, Memphis, TN) [9, 26]. One Small Kit of Infuse Bone Graft (Medtronic) which includes sterile water, sterile BMP2, and sterile absorbable collagen sponge (ACS) was used to complete this entire investigation.…”

“…For each specimen, a critical-sized calvarial defect was performed as previously described [8, 9, 26–28]. Briefly, the mice were anesthetized with isoflurane (Bethlehem, PA, USA) and a midline scalp incision was used to expose and remove the periosteum.…”