The Bone Regeneration Capacity of BMP-2 + MMP-10 Loaded Scaffolds Depends on the Tissue Status.

Patricia Garcia-Garcia,José Antonio Rodriguez,Carmen Evora,Patricia Díaz-Rodríguez,Tomas Martín,Araceli Delgado,Ricardo Reyes

doi:10.3390/pharmaceutics13070979

Patricia Garcia-Garcia, José Antonio Rodriguez + Show 5 more

Open Access

https://doi.org/10.3390/pharmaceutics13070979

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Journal: Pharmaceutics	Publication Date: Jun 29, 2021
Citations: 3	License type: CC BY 4.0

Affiliation: University of La Laguna

Abstract

Biomaterials-mediated bone formation in osteoporosis (OP) is challenging as it requires tissue growth promotion and adequate mineralization. Based on our previous findings, the development of scaffolds combining bone morphogenetic protein 2 (BMP-2) and matrix metalloproteinase 10 (MMP-10) shows promise for OP management. To test our hypothesis, scaffolds containing BMP-2 + MMP-10 at variable ratios or BMP-2 + Alendronate (ALD) were prepared. Systems were characterized and tested in vitro on healthy and OP mesenchymal stem cells and in vivo bone formation was studied on healthy and OP animals. Therapeutic molecules were efficiently encapsulated into PLGA microspheres and embedded into chitosan foams. The use of PLGA (poly(lactic-co-glycolic acid)) microspheres as therapeutic molecule reservoirs allowed them to achieve an in vitro and in vivo controlled release. A beneficial effect on the alkaline phosphatase activity of non-OP cells was observed for both combinations when compared with BMP-2 alone. This effect was not detected on OP cells where all treatments promoted a similar increase in ALP activity compared with control. The in vivo results indicated a positive effect of the BMP-2 + MMP-10 combination at both of the doses tested on tissue repair for OP mice while it had the opposite effect on non-OP animals. This fact can be explained by the scaffold’s slow-release rate and degradation that could be beneficial for delayed bone regeneration conditions but had the reverse effect on healthy animals. Therefore, the development of adequate scaffolds for bone regeneration requires consideration of the tissue catabolic/anabolic balance to obtain biomaterials with degradation/release behaviors suited for the existing tissue status.

Highlights

Bone tissue is under continuous remodeling throughout our lifetime
We have shown that matrix metalloproteinase 10 (MMP-10) accelerates bone repair by enhancing bone morphogenetic protein 2 (BMP-2)-promoted bone healing and improving the mineralization rate in a murine model of a calvaria critical size defect [26]
Polymeric microspheres were obtained by a double emulsification method using an initial aqueous internal phase of either PVA+H2O (PLGA microspheres) or PVA+Chitosan+

Summary

Introduction

Bone tissue is under continuous remodeling throughout our lifetime. Its regeneration capacity is limited by defects size, blood perfusion, age, and metabolic disorders [1]. Craniofacial bone defects or craniofacial congenital malformations generally require surgery and defects to be refilled with natural or synthetic biomaterials to promote. Often scaffolds are not enough to induce osteogenesis, and the contribution of other key elements such as progenitor cells or signaling molecules are required to ensure clinical success. The defects size and the comorbidity with other diseases altering bone tissue metabolism, compromise complete bone healing. Osteoporosis (OP) is characterized by an imbalance between the processes of bone formation and resorption and, by a delay in bone defects regeneration [2]

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