Regenerative tissue filler for breast conserving surgery and other soft tissue restoration and reconstruction needs.

Complete removal of cancerous tissue and preservation of breast cosmesis with a single breast conserving surgery (BCS) is essential for surgeons. New and better options would allow them to more consistently achieve this goal and expand the number of women that receive this preferred therapy, while minimizing the need for re-excision and revision procedures or more aggressive surgical approaches (i.e., mastectomy). We have developed and evaluated a regenerative tissue filler that is applied as a liquid to defects during BCS prior to transitioning to a fibrillar collagen scaffold with soft tissue consistency. Using a porcine simulated BCS model, the collagen filler was shown to induce a regenerative healing response, characterized by rapid cellularization, vascularization, and progressive breast tissue neogenesis, including adipose tissue and mammary glands and ducts. Unlike conventional biomaterials, no foreign body response or inflammatory-mediated "active" biodegradation was observed. The collagen filler also did not compromise simulated surgical re-excision, radiography, or ultrasonography procedures, features that are important for clinical translation. When post-BCS radiation was applied, the collagen filler and its associated tissue response were largely similar to non-irradiated conditions; however, as expected, healing was modestly slower. This in situ scaffold-forming collagen is easy to apply, conforms to patient-specific defects, and regenerates complex soft tissues in the absence of inflammation. It has significant translational potential as the first regenerative tissue filler for BCS as well as other soft tissue restoration and reconstruction needs.

Synthesis and characterization of a lubricin mimic (mLub) to reduce friction and adhesion on the articular cartilage surface.

The lubricating proteoglycan, lubricin, facilitates the remarkable low friction and wear properties of articular cartilage in the synovial joints of the body. Lubricin lines the joint surfaces and plays a protective role as a boundary lubricant in sliding contact; decreased expression of lubricin is associated with cartilage degradation and the pathogenesis of osteoarthritis. An unmet need for early osteoarthritis treatment is the development of therapeutic molecules that mimic lubricin function and yet are also resistant to enzymatic degradation common in the damaged joint. Here, we engineered a lubricin mimic (mLub) that is less susceptible to enzymatic degradation and binds to the articular surface to reduce friction. mLub was synthesized using a chondroitin sulfate backbone with type II collagen and hyaluronic acid (HA) binding peptides to promote interaction with the articular surface and synovial fluid constituents. In vitro and in vivo characterization confirmed the binding ability of mLub to isolated type II collagen and HA, and to the cartilage surface. Following trypsin treatment to the cartilage surface, application of mLub, in combination with purified or commercially available hyaluronan, reduced the coefficient of friction, and adhesion, to control levels as assessed over macro-to micro-scales by rheometry and atomic force microscopy. In vivo studies demonstrate an mLub residency time of less than 1 week. Enhanced lubrication by mLub reduces surface friction and adhesion, which may suppress the progression of degradation and cartilage loss in the joint. mLub therefore shows potential for treatment in early osteoarthritis following injury.

Host protection against deliberate bacterial contamination of an extracellular matrix bioscaffold versus Dacron mesh in a dog model of orthopedic soft tissue repair.

The resistance of two biomaterials, one synthetic and one biologic in origin, to deliberate bacterial infection was compared in a dog model of orthopedic soft tissue reconstruction. Twenty-four adult female dogs were randomly divided into two equal groups and a 2.0-cm-round full-thickness defect was created on the lateral surface of the stifle joint, leaving only the synovium and skin intact. The defect was surgically repaired with either Dacron trade mark mesh or a porcine derived extracellular matrix (ECM) scaffold material. The repair site was inoculated with 1 x 10(8) Staphylococcus aureus at the time of surgery and the dogs were survived for 28 days. Results showed a chronic pyogranulomatous inflammatory response at the Dacron trade mark implant sites versus a constructive tissue-remodeling response without residual inflammation at the ECM implant site. Three dogs in the group receiving the Dacron trade mark mesh were treated with Keflex trade mark (500 mg bid x 7 days) for signs of septicemia. A quantitative bacterial count of the implant sites at the time of sacrifice showed 6.52 x 10(5) +/- 1.2 x 10(6) and 6.5 x 10(2) +/- 1.8 x 10(3) bacteria per gram of tissue for the Dacron trade mark and ECM scaffold sites, respectively (P <.03). The ECM implant material was more resistant than the synthetic implant material to persistent infection following deliberate bacterial contamination and the ECM scaffold supported constructive tissue remodeling.