Spatially heterogeneous epidermal growth factor release from microporous annealed particle (MAP) hydrogel for improved wound closure.

Microporous annealed particle (MAP) hydrogel has been a promising scaffold platform technology to promote immediate tissue integration in injured tissue environments. The addition of growth factors has the potential to accelerate tissue integration and enhance scaffold-mediated healing. Growth factor releasing scaffolds face the translational hurdle of limited solubilized protein shelf stability; however, to address this hurdle we present a lyophilized MAP scaffold which can be effectively rehydrated directly prior to use. Our new approach includes a heterogenous MAP scaffold wherein 5% of the microgels contain immobilized heparin loaded with epidermal growth factor (EGF) at 1 µg mL-1. We demonstrate that these scaffolds, which are directly loaded with EGF following lyophilization maintain equivalent properties to scaffolds loaded passively via diffusion into water-swollen microgels, including EGF release profiles and cell migration studies that did not significantly differ. Further, these heterogeneous scaffolds exhibit a significant increase in cellular migration in vitro and quicker re-epithelialization in vivo. This progress on spatially heterogenous growth factor release from MAP scaffolds has great potential to improve complex wound treatment and advance the field of growth factor releasing scaffolds.

Ibandronate Treatment Before and After Implant Insertion Impairs Osseointegration in Aged Rats with Ovariectomy Induced Osteoporosis.

Excessive decreases in bone volume (BV) and bone mineral density (BMD) can lead to osteoporosis, potentially hindering implant osseointegration. Bisphosphonates are commonly used to combat osteoporosis by slowing osteoclast-mediated resorption; however, functional osteoclasts are integral to bone remodeling and, thus, implant osseointegration, potentially contraindicating bisphosphonate use during implantation. To optimize the use of implant technologies in patients with compromised bone structure and metabolism, we need a more complete understanding of the biological response to surface design. The goal of this study was to assess the effects of osteoporosis and bisphosphonates on osseointegration of titanium (Ti) implants with microstructured surfaces, which have been shown to support osteoblast differentiation in vitro and rapid osseointegration in vivo. Forty, 8-month-old, virgin, female CD Sprague Dawley rats underwent ovariectomy (OVX) or sham (SHOVX) surgery. After 5 weeks, animals were injected subcutaneously with either the bisphosphonate (BIS), Ibandronate (25 µg/kg), or phosphate-buffered saline (PBS) every 25 days. 1 week after the initial injection, Ø2.5mm × 3.5mm microrough (SLA; grit-blasted/acid etched) implants were placed transcortically in the distal metaphysis of each femur resulting in four groups: 1) SHOVX+PBS; 2) SHOVX+BIS; 3) OVX+PBS; and 4) OVX+BIS. After 28d, qualitative properties of the bone and implant osseointegration were assessed using micro-computed tomography (microCT), calcified histomorphometry (Van Gieson's stain), and removal torque testing. microCT revealed decreased bone volume in OVX rats, which was slowed by bisphosphonate treatment. Reduced bone-to-implant contact (BIC) was evident in OVX+PBS compared to SHOVX+PBS. Although BV/TV was increased in OVX+BIS compared to OVX+PBS, bisphosphonate treatment had no effect on BIC. Removal torque testing revealed a higher maximum torque, torsional stiffness, and torsional energy in SHOVX compared to OVX with no effects due to bisphosphonate treatment. Our results show that osseointegration is decreased in osteoporotic animals. Ibandronate halts the progression of osteoporosis but does not enhance osseointegration. © 2019 The Authors. JBMR Plus Published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.