In Vitro and in Vivo Analyses Reveal Profound Effects of Fibroblast Growth Factor 16 as a Metabolic Regulator.

The discovery of brown adipose tissue (BAT) as a key regulator of energy expenditure has sparked interest in identifying novel soluble factors capable of activating inducible BAT (iBAT) to combat obesity. Using a high content cell-based screen, we identified fibroblast growth factor 16 (FGF16) as a potent inducer of several physical and transcriptional characteristics analogous to those of both "classical" BAT and iBAT. Overexpression of Fgf16 in vivo recapitulated several of our in vitro findings, specifically the significant induction of the Ucp1 gene and UCP1 protein expression in inguinal white adipose tissue (iWAT), a common site for emergent active iBAT.

Systematic evaluation of natural scaffolds in cutaneous wound healing.

Current strategies to improve wound healing are often created from multiple components that may include a scaffold, cells, and bioactive cues. Acellular natural hydrogels are an attractive approach since the material's intrinsic biological activity can be paired with mechanical properties similar to soft tissue to induce a host's response toward healing. In this report, a systematic evaluation was conducted to study the effect of hydrogel scaffold implantation in skin healing using a human-relevant murine wound healing model.

Imine Hydrogels with Tunable Degradability for Tissue Engineering.

A shortage of available organ donors has created a need for engineered tissues. In this context, polymer-based hydrogels that break down inside the body are often used as constructs for growth factors and cells. Herein, we report imine cross-linked gels where degradation is controllable by the introduction of mixed imine cross-links.

Porous hyaluronic acid hydrogels for localized nonviral DNA delivery in a diabetic wound healing model.

The treatment of impaired wounds requires the use of biomaterials that can provide mechanical and biological queues to the surrounding environment to promote angiogenesis, granulation tissue formation, and wound closure. Porous hydrogels show promotion of angiogenesis, even in the absence of proangiogenic factors. It is hypothesized that the added delivery of nonviral DNA encoding for proangiogenic growth factors can further enhance this effect.

Non-viral DNA delivery from porous hyaluronic acid hydrogels in mice.

The lack of vascularization within tissue-engineered constructs remains the primary cause of construct failure following implantation. Porous constructs have been successful in allowing for vessel infiltration without requiring extensive matrix degradation. We hypothesized that the rate and maturity of infiltrating vessels could be enhanced by complementing the open pore structure with the added delivery of DNA encoding for angiogenic growth factors.

Chemical sintering generates uniform porous hyaluronic acid hydrogels.

The implantation of scaffolds for tissue repair has achieved only limited success due primarily to the inability to achieve vascularization within the construct. Many strategies have therefore moved to incorporate pores into the scaffolds to encourage rapid cellular infiltration and subsequent vascular ingrowth. We utilized an efficient chemical sintering technique to create a uniform network of polymethyl methacrylate (PMMA) microspheres for porous hyaluronic acid hydrogel formation.

Matrix-based gene delivery for tissue repair.

Scaffolds for tissue repair must provide structural and biochemical cues to initiate the complex cascade of events that lead to proper tissue formation. Incorporating genes into these scaffolds is an attractive alternative to protein delivery since gene delivery can be tunable to any DNA sequence and genes utilize the cells' machinery to continuously produce therapeutic proteins, leading to longer lasting transgene expression and activation of autocrine and paracrine signaling that are not activated with bulk protein delivery. In this review, we discuss the importance of scaffold design and the impact of its design parameters (e.

Design and characterization of microporous hyaluronic acid hydrogels for in vitro gene transfer to mMSCs.

The effective and sustained delivery of DNA locally could increase the applicability of gene therapy in tissue regeneration and therapeutic angiogenesis. One promising approach is to use porous hydrogel scaffolds to encapsulate and deliver nucleotides in the form of nanoparticles to the affected sites. We have designed and characterized microporous (μ-pore) hyaluronic acid hydrogels which allow for effective cell seeding in vitro post-scaffold fabrication and allow for cell spreading and proliferation without requiring high levels of degradation.

Injectable skeletal muscle matrix hydrogel promotes neovascularization and muscle cell infiltration in a hindlimb ischemia model.

Peripheral artery disease (PAD) currently affects approximately 27 million patients in Europe and North America, and if untreated, may progress to the stage of critical limb ischemia (CLI), which has implications for amputation and potential mortality. Unfortunately, few therapies exist for treating the ischemic skeletal muscle in these conditions. Biomaterials have been used to increase cell transplant survival as well as deliver growth factors to treat limb ischemia; however, existing materials do not mimic the native skeletal muscle microenvironment they are intended to treat.