Current Pharmaceutical Biotechnology - Volume 16, Issue 7, 2015

The combination of biomaterials and drug delivery strategies is a promising avenue towards improved synthetic bone substitutes. With the delivery of active species biomaterials can be provided with the bioactivity they still lack for improved bone regeneration. Recently, a lot of research efforts have been put towards this direction. Biomaterials for bone regeneration have been supplemented with small or biological molecules for improved osteoprogenitor cell recruitment, osteoinductivity, anabolic or angiogenic response, regulation of bone metabolism and others. The scope of this review is to summarize the most recent results in this field.

Hydrogels have been employed as an emerging and promising tool in tissue engineering. They find application in the interdisciplinary field that applies the basic principles of biology and engineering and act as a substitute for conventional tissue engineering materials having improved and restored tissue function. This review article discusses the important characteristic properties of polymers used for the synthesis of hydrogels, which find application in tissue engineering. Furthermore, this article also reviews the recent advances and development in hydrogels used for corneal, cartilage, skin, bone and cardiac tissue for tissue engineering applications. This article highlights the future prospects and scope of hydrogels in tissue engineering.

Protein, gene, and small molecule therapies hold great potential for facilitating comprehensive tissue repair and regeneration. However, their clinical value will rely on effective delivery systems which maximize their therapeutic benefit. Significant advances have been made in recent years towards biomaterial delivery systems to satisfy this clinical need. Here we summarize the most outstanding advances in drug delivery technology for cutaneous wound healing.

“There is a growing body of evidence suggesting that wound healing in chronic diabetic foot ulcers is growth factor dependent, and that the therapeutic delivery of these growth factors to wounds topically, has the potential ability to accelerate wound healing in conjunction with conventional wound care”. There is, however, confusion about the utility of platelet rich plasma because the studies that have evaluated them use a wide range of products (different platelet and leukocyte concentrations, different techniques and frequencies of application, very heterogeneous simple, and different endpoints) making almost impossible to compare data and draw conclusions. In this study, we have analyzed the different platelet rich plasma products from a new perspective: cost-efficiency. According to our data, we observe that platelet rich plasma is a cost-effective option that allows faster healing of ulcers, and that should be taken into account in patients with long evolution ulcers.

In this review, recent advances in biomaterials developed to favor tissue repair are presented. The focus is particularly on devices used to promote bone repair, skin wound healing and nerve regeneration. In each case, the specifications for an ideal substitute and the recent advances in the field of these biomaterials are presented. Alternatively, drug delivery systems associated with biomaterials have been developed over the recent decades to stimulate wound healing without any side effects. For this purpose, the overview presents recent advances in medicated dressings for controlled release of antibiotic to prevent infections, growth factors to promote tissue regeneration and gene delivery to modulate cell phenotype.

In the last few years several technologies are being developed for eventually repairing or replacing damaged or injured tissues and even organs. Some of these emerging technologies include the design and development of new biomaterials, the optimization of nano- and micro-technologies for drug and cell delivery, the use of autologous proteins or the application of stem cells as therapeutics. Thus, several types of stem cells, e.g. ESCs, iPSCs, MSCs, CD133+ stem cells are being evaluated for tissue regeneration purposes. The present review describes some of these emerging technologies and discusses their potential benefits and challenges.

Gene therapy is a promising strategy to deliver growth factors of interest locally in a sustained fashion and has the potential to overcome barriers to using recombinant protein therapy such as sustainability and cost. Recent studies demonstrate the safety and efficacy of non-viral delivery of plasmid DNA (pDNA) encoding a single growth factor to enhance bone healing. This pilot study is aimed at testing a non-viral gene delivery system that can deliver two different plasmids encoding two different growth factors. Polyethylenimine (PEI), a cationic polymer, was utilized as a gene delivery vector and collagen scaffold was used as a carrier to deliver the PEI-pDNA complexes encoding platelet derived growth factor B (PDGF-B) and/or vascular endothelial growth factor (VEGF). Calvarial defects in rats were implanted with scaffolds containing PEI-pPDGF-B complexes, PEI-pVEGF complexes or containing both PEIpPDGF- B and PEI-pVEGF complexes in a 1:1 ratio of plasmids. The results indicated that bone regeneration as measured using micro-CT and histological assessments was inferior in groups treated with PEI-(pPDGF-B + pVEGF) complexes, compared to defects treated with PEI-pPDGF-B complexes. This pilot study that explores the feasibility and efficacy of combinatorial non-viral gene delivery system for bone regeneration appears to provide a rationale for investigation of sequential delivery of growth factors at specific time points during the healing phases and this will be explored further in future studies.

Non-porous bare silica nanoparticles, amine modified silica nanoparticles and mesoporous particles, were evaluated as carriers for sodium ibandronate. The synthesized nanoparticles were characterized by SEM, TEM, DLS and porosity. Then, their capacity to incorporate a bisphosphonate drug (sodium ibandronate) and the in vitro release behavior was analyzed by capillary electrophoresis. Mesoporous and amine-modified particles showed higher levels of drug incorporation, 44.68 mg g-1 and 28.90 mg g-1, respectively. The release kinetics from the two types of particles was similar following a first order kinetics. However, when these particles were included into collagen hydrogels only mesoporous nanoparticles had a sustained release for over 10 days. The biocompatibility of mesoporous particles towards Saos-2 cells was also evaluated by the MTT assay observing an increase in cell viability for concentrations lower than 0.6 mg ml-1 of particles and a decrease for concentrations over 1.2 mg ml-1. Furthermore, when these particles were incubated with mesenchymal cells it was observed that they had the capacity to promote the differentiation of the cells with a significant increase in the alkaline phosphatase activity.