PEOT/PBT - βTCP composites containing zinc, zinc and copper, and zinc and cobalt induce extracellular matrix deposition upon intramuscular implantation in a mini-pig model.
Abstract
Bone healing is often compromised by comorbidities, limiting treatment success as can also be seen in the elderly. Current treatments, including autologous and allogeneic bone grafts, are associated with drawbacks. Synthetic biomaterials, particularly calcium phosphate (CaP) ceramics, show promise due to their chemical resemblance to the mineral part of native bone but are limited by suboptimal mechanical properties in the context of bone regeneration. Composite scaffolds combining CaP with polymers, such as poly(ethylene oxide terephthalate)/poly(butylene terephthalate) (PEOT/PBT) copolymers offer improved mechanical performance. Zn enhances bone formation and Cu/Co vessel formation. Therefore, to enhance osteogenic and angiogenic potential, we developed βTCP-PEOT/PBT scaffolds doped with Zn, Zn/Cu, or Zn/Co at low (15 mM) or high (45 mM) concentrations. The composites were created by combining βTCP with PEOT/PBT copolymer in a 1:1 ratio. These composites were additively manufactured into three-dimensional (3D), porous scaffolds using 3D fiber deposition techniques and have previously shown mesenchymal stem cell (MSC) differentiation and angiogenesis in vitro without external stimulants. To assess the in vivo response, we implanted the scaffolds intramuscularly in a mini-pig model for 12 weeks. All animals remained healthy, and explanted scaffolds exhibited vascularized, loose connective tissue infiltration. While no mature bone was observed at this time point, extracellular matrix (ECM) deposition was evident in all composite scaffolds but absent in polymer-only controls. Histological analysis showed ECM deposition alongside alkaline phosphatase activity, osteoclast-like cells, and macrophages, with composite scaffolds showing more consistent staining for these markers. These findings suggest an early biological response to ion-doped composite scaffolds potentially favorable to bone regeneration.