Particulated and reconstituted tissues comprising small, densely packed tissue microparticles encapsulated in a tissue specific promoting gel packed at a percolation threshold that can be transplanted into damaged tissue thereby facilitating regeneration following trauma to the tissue. The engineered microparticle construct for tissue replacement and repair, as taught herein, provides numerous benefits including (1) encouraging a regenerative response in damaged tissue regions, (2) mimicking the structural support of native tissue, (3) establishing an environment that promotes attachment, migration, and differentiation of infiltrating stem cells, and (4) providing a source of growth factors and other anti-catabolic growth factors and cytokines. Tissue specific microparticles packed together at, or past, their percolation threshold will provide the necessary mechanical environment and to best recapitulate and integrate with native tissue. The packing of microparticles, derived from the ECM of native tissue, to a concentration past the percolation point will yield both the necessary biochemical and biomechanical properties necessary for reconstituting a specific tissue.

Particulated and reconstituted tissues comprising small, densely packed tissue microparticles encapsulated in a tissue specific promoting gel packed at a percolation threshold that can be transplanted into damaged tissue thereby facilitating regeneration following trauma to the tissue. The engineered microparticle construct for tissue replacement and repair, as taught herein, provides numerous benefits including (1) encouraging a regenerative response in damaged tissue regions, (2) mimicking the structural support of native tissue, (3) establishing an environment that promotes attachment, migration, and differentiation of infiltrating stem cells, and (4) providing a source of growth factors and other anti-catabolic growth factors and cytokines. Tissue specific microparticles packed together at, or past, their percolation threshold will provide the necessary mechanical environment and to best recapitulate and integrate with native tissue. The packing of microparticles, derived from the ECM of native tissue, to a concentration past the percolation point will yield both the necessary biochemical and biomechanical properties necessary for reconstituting a specific tissue.

Provided is a lyophilized implant configured to fit at or near a bone defect to promote bone growth, the lyophilized implant containing a biodegradable polymer in an amount of about 0.1 wt. % to about 20 wt. % of the implant, mineral particles in an amount from about 0.1 wt. % to about 75 wt. % of the implant, and an oxysterol in an amount of about 5 wt. % to about 90 wt. % of the implant. Methods of making and using the implant are further provided.

Provided is a lyophilized implant configured to fit at or near a bone defect to promote bone growth, the lyophilized implant containing a biodegradable polymer in an amount of about 0.1 wt. % to about 20 wt. % of the implant, mineral particles in an amount from about 0.1 wt. % to about 75 wt. % of the implant, and an oxysterol in an amount of about 5 wt. % to about 90 wt. % of the implant. Methods of making and using the implant are further provided.

A method of making a hydroxyl-terminated thioketal diol is provided, the method comprising reacting a thioketal ester with a non-pyrophoric reducing agent to form a hydroxyl-terminated thioketal diol. The hydroxyl-terminated thioketal diol can be 2,2-(propane-2,2-diylbis(sulfanediyl)) diethanol. The non-pyrophoric reducing agent can be a sodium aluminum hydride, for example, sodium bis(2-methoxyethoxy)aluminum hydride. The thioketal ester can be dimethyl 2,2-(propane-2,2-diylbis(sulfanediyl)) diacetate. A biodegradable matrix prepared by reacting a hydroxyl-terminated thioketal diol with an isocyanate is provided. A method of making a biodegradable polyurethane composite is also provided.

A method of making a hydroxyl-terminated thioketal diol is provided, the method comprising reacting a thioketal ester with a non-pyrophoric reducing agent to form a hydroxyl-terminated thioketal diol. The hydroxyl-terminated thioketal diol can be 2,2-(propane-2,2-diylbis(sulfanediyl)) diethanol. The non-pyrophoric reducing agent can be a sodium aluminum hydride, for example, sodium bis(2-methoxyethoxy)aluminum hydride. The thioketal ester can be dimethyl 2,2-(propane-2,2-diylbis(sulfanediyl)) diacetate. A biodegradable matrix prepared by reacting a hydroxyl-terminated thioketal diol with an isocyanate is provided. A method of making a biodegradable polyurethane composite is also provided.

The invention relates to peptides including DEDE(SSD).sub.nDEG indicated by SEQ NO. 1, RRRDEDE(SSD).sub.nDEG indicated by SEQ NO. 2, RRRGDEDE(SSD).sub.nDEG indicated by SEQ NO. 3, and LKKLKKLDEDE(SSD)nDEG indicated by SEQ NO. 4, wherein n is an integer from 2 to 20. The invention also relates to phosphorylating these peptides at multiple amino acid sites by employing casein kinases. These phosphorylated peptides may be used in various applications such as forming mineralized collagen fibrils and biomimetic composites for use in tissue repair and regeneration.

The invention relates to peptides including DEDE(SSD).sub.nDEG indicated by SEQ NO. 1, RRRDEDE(SSD).sub.nDEG indicated by SEQ NO. 2, RRRGDEDE(SSD).sub.nDEG indicated by SEQ NO. 3, and LKKLKKLDEDE(SSD)nDEG indicated by SEQ NO. 4, wherein n is an integer from 2 to 20. The invention also relates to phosphorylating these peptides at multiple amino acid sites by employing casein kinases. These phosphorylated peptides may be used in various applications such as forming mineralized collagen fibrils and biomimetic composites for use in tissue repair and regeneration.

The invention relates to peptides including DEDE(SSD).sub.nDEG indicated by SEQ NO. 1, RRRDEDE(SSD).sub.nDEG indicated by SEQ NO. 2, RRRGDEDE(SSD).sub.nDEG indicated by SEQ NO. 3, and LKKLKKLDEDE(SSD)nDEG indicated by SEQ NO. 4, wherein n is an integer from 2 to 20. The invention also relates to phosphorylating these peptides at multiple amino acid sites by employing casein kinases. These phosphorylated peptides may be used in various applications such as forming mineralized collagen fibrils and biomimetic composites for use in tissue repair and regeneration.

A composite dura substitute implant for implantation at a dura defect site having a porous layer that provides an osteoconductive scaffold for bony ingrowth, a porous layer that provides a scaffold for regeneration of collagen at a dura surface, and an intervening layer for preventing cerebrospinal leakage is disclosed. The composite dura substitute implant facilitates regeneration of dura mater and promotes osteointegration with bony tissue. Methods of manufacturing such an implant and methods of treatment using such composite dura substitute implants are further disclosed.