Inkjet-based biopatterning of SDF-1β augments BMP-2-induced repair of critical size calvarial bone defects in mice

Abstract

Background A major problem in craniofacial surgery is non-healing bone defects. Autologous reconstruction remains the standard of care for these cases. Bone morphogenetic protein-2 (BMP-2) therapy has proven its clinical utility, although non-targeted adverse events occur due to the high milligram-level doses used. Ongoing efforts explore the use of different growth factors, cytokines, or chemokines, as well as co-therapy to augment healing. Methods Here we utilize inkjet-based biopatterning to load acellular DermaMatrix delivery matrices with nanogram-level doses of BMP-2, stromal cell-derived factor-1β (SDF-1β), transforming growth factor-β1 (TGF-β1), or co-therapies thereof. We tested the hypothesis that bioprinted SDF-1β co-delivery enhances BMP-2 and TGF-β1-driven osteogenesis both in-vitro and in-vivo using a mouse calvarial critical size defect (CSD) model. Results Our data showed that BMP-2 bioprinted in low-doses induced significant new bone formation by four weeks post-operation. TGF-β1 was less effective compared to BMP-2, and SDF-1β therapy did not enhance osteogenesis above control levels. However, co-delivery of BMP-2 + SDF-1β was shown to augment BMP-2-induced bone formation compared to BMP-2 alone. In contrast, co-delivery of TGF-β1 + SDF-1β decreased bone healing compared to TGF-β1 alone. This was further confirmed in vitro by osteogenic differentiation studies using MC3T3-E1 pre-osteoblasts. Conclusions Our data indicates that sustained release delivery of a low-dose growth factor therapy using biopatterning technology can aid in healing CSD injuries. SDF-1β augments the ability for BMP-2 to drive healing, a result confirmed in vivo and in vitro; however, because SDF-1β is detrimental to TGF-β1-driven osteogenesis, its’ effect on osteogenesis is not universal.

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

“…The combined scaffold did not produce better healing or more bone fill than the traditional delivery system. This outcome agrees with previous studies that found that the osteoinductive BMP2 along with an osteoconductive matrix such as ACS precipitates the greatest amount of bone growth [16, 25, 27, 31, 32]. Though we hoped that as in previous studies Talymed would precipitate denser bone growth, this did not occur when it was used with the ACS scaffold wounds [8, 9].…”

Mesenchymal stem cell expression of stromal cell‐derived factor‐1β augments bone formation in a model of local regenerative therapy

“…48 The current study presents new evidence on the importance of SDF-1β, newly recognized to be abundant in bone, in regulating BMSC-mediated osteogenesis in situ. Together with our recent reports showing SDF-1β-mediated BMP-2 healing of critical-size calvarial defects using osteoconductive matrices for local delivery 26,37 , this study supports the potential translational use of SDF-1β in bone defect repair. Future studies aim to investigate in vivo the mechanisms of SDF-1β’s modulatory effects in terms of BMSC homing, capture, and osteogenic induction of transplanted as well as endogenous stem cells and osteogenic lineage cells.…”

3D printing for the design and fabrication of polymer-based gradient scaffolds

“…In addition to mechanical cues, biochemical cues provided by the ECM or neighboring tissues and cells act in vivo to regulate and control cell fate [61–65]. To better recapitulate the native cellular environment, it is important to design systems where cells can be exposed to an engineered presentation of bioactive molecules in a 3D microenvironment.…”