Optimized Synthesis of Poly(deoxyribose) Isobutyrate, a Viscous Biomaterial for Bone Morphogenetic Protein-2 Delivery

Abstract

Injectable and phase-transitioning carriers from natural polysaccharides have great potential for the minimally invasive delivery of therapeutic proteins in the field of bone tissue engineering. In this study, a novel and highly viscous drug carrier was synthesized by a sequential process of deoxyribose polycondensation and esterification. The effect of synthesis parameters on the molecular weight, viscosity, and adhesion of the material was studied and correlated to temperature and time of polycondensation (T p and t p), time and temperature of esterification (T e and t e), and the molar ratio of the monomer (R). The formulations were evaluated for molecular weight and distribution properties using GPC, chemical structures by FTIR and NMR spectra, and rheological properties using a rheometer. Formulations illustrated a wide range of viscosities (0.736 to 2225 Pa s), adhesion (0.896 to 58.45 N), and molecular weights (637 to 4216 Da), where viscosity was significantly reduced in the presence of low amounts of solvents (10–20%). The sustained release of BSA was observed over 42 days in vitro. The biocompatibility of poly­(deoxyribose) isobutyrate (PDIB) as well as its potential as a bone morphogenetic protein delivery system was assessed in vivo using a rat ectopic bone model, where bone nodules were observed at 2 weeks. In summary, PDIB is a promising molecule with multiple applications for protein delivery, including for bone tissue engineering.

A Bioactive Coating Enhances Bone Allografts in Rat Models of Bone Formation and Critical Defect Repair

“…The methodology for PDIB synthesis has been further refined to enable the biophysical properties to be customized based on the polycondensation temperature and duration. 15 In conclusion, this study shows proof-of-concept that PDIB/BMP-2 coating can augment the anabolic action of bone allografts. PDIB represents a new delivery vehicle for bone anabolics and anti-resorptive drugs that could be used not only for allografts but also for other orthopedic applications.…”

“…In the case of ZA, this was further evidenced by the retention of the original allograft at both the core and periphery. The methodology for PDIB synthesis has been further refined to enable the biophysical properties to be customized based on the polycondensation temperature and duration …”

“…Historically, SAIB was also used as part of a more complex polymer coating system for BMP delivery in a vicryl mesh implant model . However, SAIB poorly solubilizes commercial BMP‐2 preparations including excipients such as glycine and thus our team recently designed a polycondensed deoxyribose‐based isobutyrate ester (PDIB) with tunable viscosity and protein release properties . This material is biocompatible and was able to produce ectopic bone nodules in an intramuscular delivery model.…”

“…14 However, SAIB poorly solubilizes commercial BMP-2 preparations including excipients such as glycine and thus our team recently designed a polycondensed deoxyribose-based isobutyrate ester (PDIB) with tunable viscosity and protein release properties. 15 This material is biocompatible and was able to produce ectopic bone nodules in an intramuscular delivery model. An advantage of using a viscous polymer delivery system is that it can enable sustained delivery of BMPs rather than burst release.…”

Bisphosphonate-Conjugated Photo-Crosslinking Polyanionic Hyaluronic Acid Microbeads for Controlled BMP2 Delivery and Enhanced Bone Formation Efficacy

“…1,7,8 Therefore, one of the major challenges of BMP2 therapy is the optimized delivery system that can exactly apply the titrated dose to the bone defects and also can release the BMP2 at the site of implantation without devastating leakage to other tissues. 9 To date, many materials have been screened to get the optimized delivery system of BMP2, including collagen, 10 chitosan, poly(deoxyribose) isobutyrate, 11 alginate, hydrogel, 12 collagen sponge, 13 and core−shell nanofibers. 14 One of them, hyaluronic acid (HA), exhibits excellent biocompatibility and synergistic effects on bone formation when BMP2 is applied.…”