Polymer Powder Processing of Cryomilled Polycaprolactone for Solvent‐Free Generation of Homogeneous Bioactive Tissue Engineering Scaffolds

Abstract

Synthetic polymers used in tissue engineering require functionalization with bioactive molecules to elicit specific physiological reactions. These additives must be homogeneously dispersed in order to achieve enhanced composite mechanical performance and uniform cellular response. This work demonstrates the use of a solvent-free powder processing technique to form osteoinductive scaffolds from cryomilled polycaprolactone (PCL) and tricalcium phosphate (TCP). Cryomilling is performed to achieve micrometer-sized distribution of PCL and reduce melt viscosity, thus improving TCP distribution and improving structural integrity. A breakthrough is achieved in the successful fabrication of 70 weight percentage of TCP into a continuous film structure. Following compaction and melting, PCL/TCP composite scaffolds are found to display uniform distribution of TCP throughout the PCL matrix regardless of composition. Homogeneous spatial distribution is also achieved in fabricated 3D scaffolds. When seeded onto powder-processed PCL/TCP films, mesenchymal stem cells are found to undergo robust and uniform osteogenic differentiation, indicating the potential application of this approach to biofunctionalize scaffolds for tissue engineering applications.

Osteogenic differentiation of human mesenchymal stem cells in the absence of osteogenic supplements: A surface-roughness gradient study

“…The resorbable characteristic of the implant-material is particularly important in pediatric trauma, given that the skeleton of the pediatric patients is not fully developed and the implant size will eventually mismatch the growing body, which would require secondary corrective surgeries. Polycaprolactone (PCL) is a resorbable polymer, which has been thoroughly studied for its biocompatibility, degradation behavior, mechanical properties and easy manipulation into different scaffold-architectures by a wide range of processing techniques [3][4][5][6][7]. FDA-approved for its use in several medical devices, PCL is a particularly interesting option to explore for low-load-bearing applications, such as craniofacial bone solutions [4,8].…”

Fabrication and evaluation of poly(lactic acid), chitosan, and tricalcium phosphate biocomposites for guided bone regeneration

“…The sample‐containing vials were loaded into the freezer mill (6870; SPEX, Metuchen, NJ) which was maintained at −196 °C. The samples were cryomilled for 20 min (4 milling cycles) . A cooling time of 1 min was allowed between successive cycles and a precool time of 15 min was utilized to ensure homogeneity in temperature at the time of milling .…”

The enhanced osteogenesis and osteointegration of 3-DP PCL scaffolds via structural and functional optimization using collagen networks

“…10 Synthetic polymers (e.g., PCL and PLGA) display favorable mechanical functionality, good processability and controllable biodegradability, but are limited by their inherent poor bioactivity, leading to poor cellular attachment and brosis encapsulation. 11 Therefore, to fabricate clinically related products that are translatable from bench to bedside, optimal balance between mechanical functionality, biological performance and fabrication processability must be considered as a priority.…”

“…11,[18][19][20] However, aggregation and phase separation lead to inhomogeneous dispersions and the masking of ceramic particles by the polymer, resulting in the exposure of the ceramic on the scaffold surface and the hindering of cell attachment and proliferation due to the hydrophobic nature of PCL. 11,21 Previously, Pati 16 has fabricated cell-laid ECM ornamented 3DP PCL/b-TCP scaffolds, overcoming the above disadvantages and supporting osteoblastic differentiation and promoting greater bone formation. This cell-laid ECM ornamenting, mimicking the ECM of bone tissue, showed tailorable physical properties and favorable bioactivity, however, this celllaid method is sophisticated and time consuming.…”