Methods of bioprinting a bio-ink construct on an internal tissue defect or a chondral defect during a minimally invasive surgery on an individual in need thereof are provided, comprising: visualizing the defect; positioning a bioprinter comprising a printhead within proximity of or in contact with the defect; and ejecting a bio-ink from the printhead onto the defect to form a bio-ink layer, thereby generating a bio-ink construct. Further provided are systems for bioprinting a bio-ink construct on an internal tissue defect during a minimally invasive surgery on an individual in need thereof, comprising a control system, an endoscope, and a bioprinter comprising a printhead.

Disclosed herein are compounds of formula (I)

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and therapeutic methods of treatment with compounds of formula (I), wherein L.sup.1, L.sup.2, L.sup.4, R.sup.1, R.sup.4, R.sup.5, R.sup.6, and s are as defined in the specification. Compounds of formula (I) are EP4 agonists useful in the treatment of glaucoma, neuropathic pain, and related disorders.

Disclosed are various bioactive grafts and methods of making the same. In one embodiment, bone material is harvested from a donor. The harvested bone material is exposed to a lysing agent, the lysing agent configured to release growth factors and bioactive materials from cellular material of the harvested bone material. The harvested bone material is then rinsed with a rinsing agent. The pH of the harvested bone material is substantially neutralized.

Provided are compositions and methods for a scaffold coated with a primer coating and a mineral coating. Also provided is a composition for a scaffold having a mineral coating similar to bone. Also provided is a method for mineral coating a scaffold so as to promote mineral coating of the scaffold with a plate-like nanostructure and a carbonate-substituted, calcium-deficient hydroxyapatite phase.

The present invention provides a method of bone regeneration for repairing a bone defect in a subject in need thereof. The method comprises the use of blood aspirate of the mandible bone marrow with the use of xenogen bone support.

Grafts modified with one or more bioactive substances are provided, as well as methods to make and use them. More particularly, the present invention relates to modified grafts having characteristics which facilitate tissue generation, repair, and reconstruction, and which are modified with bioactive substances, such as one or more proteins and minerals, whose bioactivity further facilitates tissue generation, repair, and reconstruction. Methods for producing the modified grafts include depositing the one or more bioactive substances onto, into, or both, a substrate material. In certain exemplary embodiments, the substrate material comprises a tissue derived matrix produced by processing one or more tissue samples, and the bioactive materials are precipitated from a solution produced during that processing, such as during demineralization of bone tissue samples or delipidation of adipose tissue samples, wherein the one or more bioactive substances comprise proteins and minerals endogenous to bone or adipose tissue, respectively.

Methods for making surgical implants (or grafts) for the repair of bone defects, and more particularly, surgical implants that include demineralized bone fibers, are disclosed. Also disclosed are methods for increasing the wettability and ensuring uniform density of such implants. The surgical implants have a wettability time of less than 5 minutes and a residual moisture content of less than 6% by weight, and they remain cohesive and retain their shape upon complete rehydration.

A bone grinder is provided herein. The bone grinder may have a grinding chamber, an intermediate zone, and a primary cutting element and a secondary cutting element. The intermediate zone may have a first wall and a second wall within the grinding chamber, and the intermediate zone may separate the primary cutting element from the secondary cutting element. The first wall and the second wall may slope inward such that a distance between the first wall and the second wall generally decreases from the primary cutting element to the secondary cutting element. The primary cutting element and the secondary cutting element may be positioned within the grinding chamber to sequentially perform primary cutting operations and secondary cutting operations on a bone. A drive mechanism may operatively engage the primary cutting element and the secondary cutting element.

3D native tissue-derived scaffolding materials are made in various formats, including but not limited to hydrogel, sponge, fibers, microspheres, and films, all of which function to better preserve natural extracellular matrix molecules and to recapitulate the natural tissue environment, thereby effectively guiding tissue regeneration. Tissue-derived scaffolds are prepared by incorporating a homogenized tissue-derived suspension into a polymeric solution of synthetic, natural, or hybrid polymers. Such tissue-derived scaffolds and scaffolding materials have a variety of utilities, including: the creation of 3D tissue models such as skin, bone, liver, pancreas, lung, and so on; facilitation of studies on cell-matrix interactions; and the fabrication of implantable scaffolding materials for guided tissue formation in vivo. The tissue-derived scaffolds and scaffolding materials also provide the opportunity to correlate the functions of extracellular matrix with tissue regeneration and cancer metastasis, for example.

The data presented herein relates to therapeutic compositions of mesenchymal stem cells (MSCs). In particular, pharmaceutically acceptable MSC compostions are xenogen-free and do not have immunological adverse effects. Mesenchymal stem cells expanded in a cell culture media comprising bone marrow supernatant produce xenogen-free mesenchymal stem cells. Such xenogen-free MSC compositions improve therapy for medical conditions including, but not limited to, osteoarthritis, cardiovascular disorders and/or diabetes.