Delivering Proangiogenic Factors from 3D‐Printed Polycaprolactone Scaffolds for Vascularized Bone Regeneration

Abstract

Natural bone is a highly vascularized tissue that relies on the vasculature for blood and nutrients supply to maintain skeletal integrity. Inadequacy of neovascularization may compromise the tissue ingrowth to the implanted scaffolds, and eventually results in failure for the repair. To tackle this issue and enhance self-vascularized bone regeneration, herein a 3D biomimetic selective lasersintering (SLS) derived scaffold, with an angiogenic growth factor immobilized on its surface, that can be released in a controlled manner is proposed. To this end, a porous polycaprolactone/hydroxyapatite (PCL/HA) scaffold is prepared via the SLS technique, which is further modified with vascular endothelial growth factor (VEGF) by coprecipitation with apatite. The resultant scaffold (PCL/HA/VEGF) has an excellent cytocompatibility, and subcutaneous implantation experiment shows that the VEGF-loaded scaffold significantly enhances the blood vessel formation compared with the VEGF-free control. It is further demonstrated that the PCL/HA/VEGF scaffold is able to enhance the in vivo bone regeneration in a rat cranial defect model. Taken together, the current study provides not only a feasible and promising scaffold candidate to enhance the vascularized bone regeneration, but also a general strategy to overcome the inadequate vascularization issue for the repair of other tissue and organs.

Bioink Formulations for Bone Tissue Regeneration

“…It appears that an improved biocompatibility, using smart materials, will facilitate the differentiation and proliferation characteristics of the encapsulated stem cells (Anjum et al, 2016), and the vascularization of 3D scaffolds after implantation (Santos and Reis, 2010;Lee et al, 2014;He et al, 2019;Liu et al, 2020). The responsiveness of such smart materials can be reflected by a precise regulation of the release and binding of growth factors, which promotes the production of cell instructive matrices with tissue healing and regeneration functions, and contributes to the in situ vascularization of tissue repair.…”

A review of biomimetic scaffolds for bone regeneration: Toward a cell‐free strategy

“…First, the PCL/HA composite microspheres were constructed through an emulsification solvent evaporation approach, then, the microsphere‐based porous scaffolds were prepared by selective lasersintering (SLS). Finally, the surface of the composite scaffold was modified with VEGF165 labeled with fluorescent RBITC for visualizing the vascularized bone regeneration in vivo 256 …”

Tissue Engineering Through 3D Bioprinting to Recreate and Study Bone Disease

“…Further considering bone acting as a bed releasing the drug, Liu et al tested a porous polycaprolactone/hydroxyapatite (PCL/HA) scaffold, modified with vascular endothelial growth factor (VEGF). This scaffold was analyzed for its effects on cell adhesion, proliferation, and vascularized bone regeneration [ 46 ]. Other materials that have been fabricated and introduced as bone are: silver nanoparticles (AgNPs) trapped into the polydopamine (pDA) layer, apatite [ 47 ], poly(glycolic acid)/hydroxyapatite [ 48 ], and nano-hydroxyapatite (nHAp) polyoxymethylene composites on 316L stainless steel [ 49 ].…”