Comparison of Scaffolds Fabricated via 3D Printing and Salt Leaching: In Vivo Imaging, Biodegradation, and Inflammation.

In this work, we prepared fluorescently labeled poly(ε-caprolactone-ran-lactic acid) (PCLA-F) as a biomaterial to fabricate three-dimensional (3D) scaffolds via salt leaching and 3D printing. The salt-leached PCLA-F scaffold was fabricated using NaCl and methylene chloride, and it had an irregular, interconnected 3D structure. The printed PCLA-F scaffold was fabricated using a fused deposition modeling printer, and it had a layered, orthogonally oriented 3D structure.

An injectable cationic hydrogel electrostatically interacted with BMP2 to enhance in vivo osteogenic differentiation of human turbinate mesenchymal stem cells.

We have designed and characterized an injectable, electrostatically bonded, in situ-forming hydrogel system consisting of a cationic polyelectrolyte [(methoxy)polyethylene glycol-b-(poly(ε-caprolactone)-ran-poly(L-lactic acid)] (MP) copolymer derivatized with an amine group (MP-NH) and anionic BMP2. To the best of our knowledge, there have been hardly any studies that have investigated electrostatically bonded, in situ-forming hydrogel systems consisting of MP-NH and BMP2, with respect to how they promote in vivo osteogenic differentiation of human turbinate mesenchymal stem cells (hTMSCs). Injectable formulations almost immediately formed an electrostatically loaded hydrogel depot containing BMP2, upon injection into mice.

Effect of Drug Carrier Melting Points on Drug Release of Dexamethasone-Loaded Microspheres.

Here, we examined the effect of melting point of drug carriers on drug release of dexamethasone (Dex)-loaded microspheres. We prepared poly(L-lactide-ran-ε-caprolactone) (PLC) copolymers with varying compositions of poly(ε-caprolactone) (PCL) and poly(L-lactide) (PLLA). As the PLLA content increased, the melting points of PLC copolymers decreased from 61 to 43 °C.

Bone regeneration by means of a three-dimensional printed scaffold in a rat cranial defect.

Recently, computer-designed three-dimensional (3D) printing techniques have emerged as an active research area with almost unlimited possibilities. In this study, we used a computer-designed 3D scaffold to drive new bone formation in a bone defect. Poly-L-lactide (PLLA) and bioactive β-tricalcium phosphate (TCP) were simply mixed to prepare ink.

Synergistic anti-tumor activity through combinational intratumoral injection of an in-situ injectable drug depot.

Here, we describe combinational chemotherapy via intratumoral injection of doxorubicin (Dox) and 5-fluorouracil (Fu) to enhance the efficacy and reduce the toxicity of systemically administered Fu and Dox in cancer patients. As the key concept in this work, mixture formulations of Dox-loaded microcapsules (Dox-M) and Fu-loaded Pluronic(®) hydrogels (Fu-HP) or Fu-loaded diblock copolymer hydrogels (Fu-HC) have been employed as drug depots. The in vitro and in vivo drug depot was designed as a formulation of Dox-M dispersed inside an outer shell of Fu-HP or Fu-HC after injection.

Biodegradable poly(lactide-co-glycolide-co-ε-caprolactone) block copolymers - evaluation as drug carriers for a localized and sustained delivery system.

To develop an appropriate drug carrier for drug delivery systems, we prepared random poly(lactide-co-glycolide-co-ε-caprolactone) (PLGC) copolymers in comparison to commercial poly(lactic acid-co-glycolic acid) (PLGA) grades. The molecular weights of PLGC copolymers varied from 20k to 90k g mol in the total polyester segments, when poly-l-lactic acid (PLLA), polyglycolic acid (PGA), and polycaprolactone (PCL) compositions were kept constant. The lengths of PLGC copolymers varied from 10 : 10 : 80 to 40 : 40 : 20 in the PLLA : PGA : PCL segments, when the molecular weights of the total polyester segments were kept constant.

A computer-designed scaffold for bone regeneration within cranial defect using human dental pulp stem cells.

A computer-designed, solvent-free scaffold offer several potential advantages such as ease of customized manufacture and in vivo safety. In this work, we firstly used a computer-designed, solvent-free scaffold and human dental pulp stem cells (hDPSCs) to regenerate neo-bone within cranial bone defects. The hDPSCs expressed mesenchymal stem cell markers and served as an abundant source of stem cells with a high proliferation rate.

Evaluation of small intestine submucosa and poly(caprolactone-co-lactide) conduits for peripheral nerve regeneration.

The present study employed nerve guidance conduits (NGCs) only, which were made of small intestine submucosa (SIS) and poly(caprolactone-co-lactide) (PCLA) to promote nerve regeneration in a peripheral nerve injury (PNI) model with nerve defects of 15 mm. The SIS- and PCLA-NGCs were easily prepared by rolling of a SIS sheet and a bioplotter using PCLA, respectively. The prepared SIS- and PCLA-NGCs fulfilled the general requirement for use as artificial peripheral NGCs such as easy fabrication, reproducibility for mass production, suturability, sterilizability, wettability, and proper mechanical properties to resist collapsing when applied to in vivo implantation.

In vivo osteogenic differentiation of human turbinate mesenchymal stem cells in an injectable in situ-forming hydrogel.

Human turbinate mesenchymal stromal cells (hTMSCs) are an alternate source of adult stem cells for regenerative medicine. In this work, we demonstrated that hTMSCs are easily harvested from turbinate tissue using a minimal surgical procedure. hTMSCs showed positive expression of mesenchymal stem cell markers and proliferated at a high rate.

Preparation of three-dimensional scaffolds by using solid freeform fabrication and feasibility study of the scaffolds.

To adapt biomaterials for solid freeform fabrication (SFF), methoxy polyethylene glycol (MPEG)-(PLLA-co-PCL) (LC) block copolymers were prepared using MPEG as the initiator to precisely control the molecular weight of PLLA and PCL. The LC block copolymers were designed such that the PLLA and PCL content varied and their molecular weights were within 200-1000 kDa. The cylindrical LC scaffolds were prepared by using LC block copolymers in SFF.

Injectable in situ-forming hydrogel for cartilage tissue engineering.

Methoxy polyethylene glycol-poly(ε-caprolactone) (MPEG-PCL; MP) diblock copolymers undergo a solution-to-gel phase transition at body temperature and serve as ideal biomaterials for drug delivery and tissue engineering. Here, we examined the potential use of a chondrocyte-loaded MP solution as an injectable, in situ-forming hydrogel for cartilage regeneration. The chondrocyte-MP solution underwent a temperature-dependent solution-to-gel phase transition in vitro, as shown by an increase in viscosity from 1 cP at 20-30 °C to 1.

Injectable intratumoral hydrogel as 5-fluorouracil drug depot.

The effectiveness of systemically administered anticancer treatments is limited by difficulties in achieving therapeutic doses within tumors, a problem that is complicated by dose-limiting side effects to normal tissue. To increase the efficacy and reduce the toxicity of systemically administered anticancer 5-fluorouracil (5-Fu) treatments in patients, intratumoral administration of an injectable hydrogel has been evaluated in the current work. The MPEG-b-(PCL-ran-PLLA) diblock copolymer (MCL) containing 5-Fu existed in an emulsion-sol state at room temperature and rapidly gelled in vivo at the body temperature.

Preparation of polymeric micelles consisting of poly(propylene glycol) and poly(caprolactone).

The ring-opening polymerization of epsilon-caprolactone (CL) was carried out with polypropylene glycol (PPG) as an initiator in the presence of the monomer activator HCl. Et2O to synthesize poly(epsilon-caprolactone)-poly(propyleneglycol)-poly(epsilon-caprolactone) (PCL-PPG-PCL) triblock copolymers with change of length PPG and PCL. The micelle formation of PCL-PPG-PCL triblock copolymers in an aqueous phase was confirmed by NMR, dynamic light scattering and fluorescence techniques.

An injectable biodegradable temperature-responsive gel with an adjustable persistence window.

ɛ-Caprolactone (CL) and 3-benzyloxymethyl-6-methyl-1,4-dioxane-2,5-dion (fLA), with a benzyloxymethyl group at the 3-position of the lactide, were randomly copolymerized. The methoxy polyethylene glycol (MPEG)-b-[poly(ɛ-caprolactone)-ran-poly(3-benzyloxymethyl lactide) (PCL-ran-PfLA)] diblock copolymers were designed such that the PfLA content (0-15 mol%) in the PCL segment was varied. The MPEG-b-(PCL-ran-PfLA) diblock copolymers were derivatized by introducing a pendant benzyl group (MC(x)L(y)-OBn), hydroxyl group (MC(x)L(y)-OH), or carboxylic acid group (MC(x)L(y)-COOH) at the PfLA segment.